PMCC PMCC

Search tips
Search criteria

Advanced
Results 1-25 (1404611)

Clipboard (0)
None

Related Articles

1.  Bacterial Vaginosis Associated with Increased Risk of Female-to-Male HIV-1 Transmission: A Prospective Cohort Analysis among African Couples 
PLoS Medicine  2012;9(6):e1001251.
In a prospective study, Craig Cohen and colleagues investigate the association between bacterial vaginosis and the risk of female-to-male HIV-1 transmission.
Background
Bacterial vaginosis (BV), a disruption of the normal vaginal flora, has been associated with a 60% increased risk of HIV-1 acquisition in women and higher concentration of HIV-1 RNA in the genital tract of HIV-1–infected women. However, whether BV, which is present in up to half of African HIV-1–infected women, is associated with an increase in HIV-1 transmission to male partners has not been assessed in previous studies.
Methods and Findings
We assessed the association between BV on female-to-male HIV-1 transmission risk in a prospective study of 2,236 HIV-1–seropositive women and their HIV-1 uninfected male partners from seven African countries from a randomized placebo-controlled trial that enrolled heterosexual African adults who were seropositive for both HIV-1 and herpes simplex virus (HSV)-2, and their HIV-1–seronegative partners. Participants were followed for up to 24 months; every three months, vaginal swabs were obtained from female partners for Gram stain and male partners were tested for HIV-1. BV and normal vaginal flora were defined as a Nugent score of 7–10 and 0–3, respectively. To reduce misclassification, HIV-1 sequence analysis of viruses from seroconverters and their partners was performed to determine linkage of HIV-1 transmissions. Overall, 50 incident HIV-1 infections occurred in men in which the HIV-1–infected female partner had an evaluable vaginal Gram stain. HIV-1 incidence in men whose HIV-1–infected female partners had BV was 2.91 versus 0.76 per 100 person-years in men whose female partners had normal vaginal flora (hazard ratio 3.62, 95% CI 1.74–7.52). After controlling for sociodemographic factors, sexual behavior, male circumcision, sexually transmitted infections, pregnancy, and plasma HIV-1 RNA levels in female partners, BV was associated with a greater than 3-fold increased risk of female-to-male HIV-1 transmission (adjusted hazard ratio 3.17, 95% CI 1.37–7.33).
Conclusions
This study identified an association between BV and increased risk of HIV-1 transmission to male partners. Several limitations may affect the generalizability of our results including: all participants underwent couples HIV counseling and testing and enrolled in an HIV-1 prevention trial, and index participants had a baseline CD4 count ≥250 cells/mm3 and were HSV-2 seropositive. Given the high prevalence of BV and the association of BV with increased risk of both female HIV-1 acquisition and transmission found in our study, if this association proves to be causal, BV could be responsible for a substantial proportion of new HIV-1 infections in Africa. Normalization of vaginal flora in HIV-1–infected women could mitigate female-to-male HIV-1 transmission.
Trial Registration: ClinicalTrials.com NCT00194519
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Since the first reported case of AIDS in 1981, the number of people infected with HIV, the virus that causes AIDS, has risen steadily. By the end of 2010, 34 million people were living with HIV/AIDS. At the beginning of the epidemic more men than women were infected with HIV. Now, however, 50% of all adults infected with HIV are women and in sub-Saharan Africa, where two-thirds of HIV-positive people live, women account for 59% of people living with HIV. Moreover, among 15–24 year-olds, women are eight times more likely than men to be HIV-positive. This pattern of infection has developed because most people in sub-Saharan Africa contract HIV through unprotected heterosexual sex. The risk of HIV transmission for both men and women in Africa and elsewhere can be reduced by abstaining from sex, by only having one or a few partners, by always using condoms, and by male circumcision. In addition, several studies suggest that antiretroviral therapy (ART) greatly reduces HIV transmission.
Why Was This Study Done?
Unfortunately, in sub-Saharan Africa, only about a fifth of HIV-positive people are currently receiving ART, which means that there is an urgent need to find other effective ways to reduce HIV transmission in this region. In this prospective cohort study (a type of study that follows a group of people for some time to see which personal characteristics are associated with disease development), the researchers investigate whether bacterial vaginosis—a condition in which harmful bacteria disrupt the normal vaginal flora—increases the risk of female-to-male HIV transmission among African couples. Bacterial vaginosis, which is extremely common in sub-Saharan Africa, has been associated with an increased risk of HIV acquisition in women and induces viral replication and shedding in the vagina in HIV-positive women, which may mean that HIV-positive women with bacterial vaginosis are more likely to transmit HIV to their male partners than women without this condition. If this is the case, then interventions that reduce the incidence of bacterial vaginosis might be valuable HIV prevention strategies.
What Did the Researchers Do and Find?
The researchers analyzed data collected from 2,236 heterosexual African couples enrolled in a clinical trial (the Partners in Prevention HSV/HIV Transmission Study) whose primary aim was to investigate whether suppression of herpes simplex virus infection could prevent HIV transmission. In all the couples, the woman was HIV-positive and the man was initially HIV-negative. The female partners were examined every three months for the presence of bacterial vaginosis and the male partners were tested regularly for HIV infection. The researchers also determined whether the men who became HIV-positive were infected with the same HIV strain as their partner to check that their infection had been acquired from this partner. The HIV incidence in men whose partners had bacterial vaginosis was 2.9 per 100 person-years (that is, 2.9 out of every 100 men became HIV-positive per year) whereas the HIV incidence in men whose partners had a normal vaginal flora was 0.76 per 100 person-years. After controlling for factors that might affect the risk of HIV transmission such as male circumcision and viral levels in female partner's blood, the researchers estimated that bacterial vaginosis was associated with a 3.17-fold increased risk of female-to-male HIV transmission in their study population.
What Do These Findings Mean?
These findings suggest that HIV-positive African women with bacterial vaginosis are more than three times as likely to transmit HIV to their male partners as those with a normal vaginal flora. It is possible that some unknown characteristic of the men in this study might have increased both their own risk of HIV infection and their partner's risk of bacterial vaginosis. Nevertheless, because bacterial vaginosis is so common in Africa (half of the women in this study had bacterial vaginosis at least once during follow-up) and because this condition is associated with both female HIV acquisition and transmission, these findings suggest that bacterial vaginosis could be responsible for a substantial proportion of new HIV infections in Africa. Normalization of vaginal flora in HIV-infected women by frequent presumptive treatment with antimicrobials (treatment with a curative dose of antibiotics without testing for bacterial vaginosis) or possibly by treatment with probiotics (live “good” bacteria) might, therefore, reduce female-to-male HIV transmission in sub-Saharan Africa.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001251.
Information is available from the US National Institute of Allergy and infectious diseases on all aspects of HIV infection and AIDS and on bacterial vaginosis
The US Centers for Disease Control and Prevention has information on all aspects of HIV/AIDS, including specific information about HIV/AIDS and women; it also has information on bacterial vaginosis (in English and Spanish)
NAM/aidsmap provides basic information about HIV/AIDS, and summaries of recent research findings on HIV care and treatment, and information on bacterial vaginosis and HIV transmission (in several languages)
Information is available from Avert, an international AIDS nonprofit group on many aspects of HIV/AIDS, including detailed information on HIV and AIDS prevention, on women, HIV and AIDS and on HIV/AIDS in Africa (in English and Spanish); personal stories of women living with HIV are available; the website Healthtalkonline also provides personal stories about living with HIV
More information about the Partners in Prevention HSV/HIV Transmission Study is available
doi:10.1371/journal.pmed.1001251
PMCID: PMC3383741  PMID: 22745608
2.  Intermuscular Adipose Tissue and Metabolic Associations in HIV Infection 
Obesity (Silver Spring, Md.)  2010;19(2):283-291.
Intermuscular adipose tissue (IMAT) is associated with metabolic abnormalities similar to those associated with visceral adipose tissue (VAT). Increased IMAT has been found in obese human immunodeficiency virus (HIV)-infected women. We hypothesized that IMAT, like VAT, would be similar or increased in HIV-infected persons compared with healthy controls, despite decreases in subcutaneous adipose tissue (SAT) found in HIV infection. In the second FRAM (Study of Fat Redistribution and Metabolic Change in HIV infection) exam, we studied 425 HIV-infected subjects and 211 controls (from the Coronary Artery Risk Development in Young Adults study) who had regional AT and skeletal muscle (SM) measured by magnetic resonance imaging (MRI). Multivariable linear regression identified factors associated with IMAT and its association with metabolites. Total IMAT was 51% lower in HIV-infected participants compared with controls (P = 0.003). The HIV effect was attenuated after multivariable adjustment (to −28%, P < 0.0001 in men and −3.6%, P = 0.70 in women). Higher quantities of leg SAT, upper-trunk SAT, and VAT were associated with higher IMAT in HIV-infected participants, with weaker associations in controls. Stavudine use was associated with lower IMAT and SAT, but showed little relationship with VAT. In multivariable analyses, regional IMAT was associated with insulin resistance and triglycerides (TGs). Contrary to expectation, IMAT is not increased in HIV infection; after controlling for demographics, lifestyle, VAT, SAT, and SM, HIV+ men have lower IMAT compared with controls, whereas values for women are similar. Stavudine exposure is associated with both decreased IMAT and SAT, suggesting that IMAT shares cellular origins with SAT.
doi:10.1038/oby.2010.115
PMCID: PMC3731045  PMID: 20539305
3.  Gender Differences in Survival among Adult Patients Starting Antiretroviral Therapy in South Africa: A Multicentre Cohort Study 
PLoS Medicine  2012;9(9):e1001304.
Morna Cornell and colleagues investigate differences in mortality for HIV-positive men and women on antiretroviral therapy in South Africa.
Background
Increased mortality among men on antiretroviral therapy (ART) has been documented but remains poorly understood. We examined the magnitude of and risk factors for gender differences in mortality on ART.
Methods and Findings
Analyses included 46,201 ART-naïve adults starting ART between January 2002 and December 2009 in eight ART programmes across South Africa (SA). Patients were followed from initiation of ART to outcome or analysis closure. The primary outcome was mortality; secondary outcomes were loss to follow-up (LTF), virologic suppression, and CD4+ cell count responses. Survival analyses were used to examine the hazard of death on ART by gender. Sensitivity analyses were limited to patients who were virologically suppressed and patients whose CD4+ cell count reached >200 cells/µl. We compared gender differences in mortality among HIV+ patients on ART with mortality in an age-standardised HIV-negative population.
Among 46,201 adults (65% female, median age 35 years), during 77,578 person-years of follow-up, men had lower median CD4+ cell counts than women (85 versus 110 cells/µl, p<0.001), were more likely to be classified WHO stage III/IV (86 versus 77%, p<0.001), and had higher mortality in crude (8.5 versus 5.7 deaths/100 person-years, p<0.001) and adjusted analyses (adjusted hazard ratio [AHR] 1.31, 95% CI 1.22–1.41). After 36 months on ART, men were more likely than women to be truly LTF (AHR 1.20, 95% CI 1.12–1.28) but not to die after LTF (AHR 1.04, 95% CI 0.86–1.25). Findings were consistent across all eight programmes. Virologic suppression was similar by gender; women had slightly better immunologic responses than men. Notably, the observed gender differences in mortality on ART were smaller than gender differences in age-standardised death rates in the HIV-negative South African population. Over time, non-HIV mortality appeared to account for an increasing proportion of observed mortality. The analysis was limited by missing data on baseline HIV disease characteristics, and we did not observe directly mortality in HIV-negative populations where the participating cohorts were located.
Conclusions
HIV-infected men have higher mortality on ART than women in South African programmes, but these differences are only partly explained by more advanced HIV disease at the time of ART initiation, differential LTF and subsequent mortality, and differences in responses to treatment. The observed differences in mortality on ART may be best explained by background differences in mortality between men and women in the South African population unrelated to the HIV/AIDS epidemic.
Please see later in the article for the Editors' Summary.
Editors' Summary
Background
About 34 million people (most living in low- and middle-income countries) are currently infected with HIV, the virus that causes AIDS. HIV destroys CD4 lymphocytes and other immune system cells, leaving infected individuals susceptible to other infections. Early in the AIDS epidemic, most HIV-infected people died within 10 years of becoming infected. Then, in 1996, antiretroviral therapy (ART)—cocktails of drugs that keep HIV in check—became available. For people living in affluent countries, HIV/AIDS became a chronic condition. However, ART was expensive and, for people living in poorer countries, HIV/AIDS remained a fatal illness. In 2003, this situation was declared a global emergency, and governments and international agencies began to implement plans to increase ART coverage in resource-limited countries. Since then, ART programs in these countries have grown rapidly. In South Africa, for example, about 52% of the 3.14 million adults in need of ART were receiving an ART regimen recommended by the World Health Organization by the end of 2010.
Why Was This Study Done?
The outcomes of ART programs in resource-limited countries need to be evaluated thoroughly so that these programs can be optimized. One area of concern to ART providers is that of gender differences in survival among patients receiving treatment. In sub-Saharan Africa, for example, men are more likely to die than women while receiving ART. This gender difference in mortality may arise because men initiating ART in many African ART programs have more advanced HIV disease than women (early ART initiation is associated with better outcomes than late initiation) or because men are more likely to be lost to follow-up than women (failure to continue treatment is associated with death). Other possible explanations for gender differentials in mortality on ART include gender differences in immunologic and virologic responses to treatment (increased numbers of immune system cells and reduced amounts of virus in the blood, respectively). In this multicenter cohort study, the researchers examine the size of, and risk factors for, gender differences in mortality on ART in South Africa by examining data collected from adults starting ART at International Epidemiologic Databases to Evaluate AIDS South Africa (IeDEA-SA) collaboration sites.
What Did the Researchers Do and Find?
The researchers analyzed data collected from 46,201 ART-naïve adults who started ART between 2002 and 2009 in eight IeDEA-SA ART programs. At ART initiation, men had a lower CD4 count on average and were more likely to have advanced HIV disease than women. During the study, after allowing for factors likely to affect mortality such as HIV disease stage at initiation, men on ART had a 31% higher risk of dying than women. Men were more likely to be lost to follow-up than women, but men and women who were lost to follow-up were equally likely to die. Women had a slightly better immunological response to ART than men but virologic suppression was similar in both genders. Importantly, in analyses of mortality limited to individuals who were virologically suppressed at 12 months and to patients who had a good immunological response to ART, men still had a higher risk of death than women. However, the gender differences in mortality on ART were smaller than the gender differences in age-standardized mortality in the HIV-negative South African population.
What Do These Findings Mean?
These analyses show that among South African patients initiating ART between 2002 and 2009, men were more likely to die than women but that this gender difference in mortality on ART cannot be completely explained by gender differences in baseline characteristics, loss to follow-up, or virologic and/or immunologic responses. Instead, the observed gender differences in mortality can best be explained by background gender differences in mortality in the whole South African population. Because substantial amounts of data were missing in this study (for example, HIV disease stage was not available for all the patients), these findings need to be interpreted cautiously. Moreover, similar studies need to be done in other settings to investigate whether they are generalizable to the South African national ART program and to other countries. If confirmed, however, these findings suggest that the root causes of gender differences in mortality on ART may be unrelated to HIV/AIDS or to the characteristics of ART programs.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001304.
Information is available from the US National Institute of Allergy and Infectious Diseases on HIV infection and AIDS
Information on the treatment of HIV/AIDS in South Africa is available from the Southern African HIV Clinicians Society
NAM/aidsmap provides basic information about HIV/AIDS and summaries of recent research findings on HIV care and treatment
Information is available from Avert, an international AIDS charity on many aspects of HIV/AIDS, including information on HIV/AIDS treatment and care, and on HIV/AIDS in South Africa (in English and Spanish)
WHO provides information about universal access to AIDS treatment (in several languages); its 2010 ART guidelines can be downloaded
Information about the IeDEA-SA collaboration is available
The Treatment Action Campaign provides information on antiretroviral therapy and South African HIV statistics
Patient stories about living with HIV/AIDS are available through Avert; the nonprofit website Healthtalkonline also provides personal stories about living with HIV, including stories about taking anti-HIV drugs and the challenges of anti-HIV drugs
doi:10.1371/journal.pmed.1001304
PMCID: PMC3433409  PMID: 22973181
4.  The Safety of Adult Male Circumcision in HIV-Infected and Uninfected Men in Rakai, Uganda 
PLoS Medicine  2008;5(6):e116.
Background
The objective of the study was to compare rates of adverse events (AEs) related to male circumcision (MC) in HIV-positive and HIV-negative men in order to provide guidance for MC programs that may provide services to HIV-infected and uninfected men.
Methods and Findings
A total of 2,326 HIV-negative and 420 HIV-positive men (World Health Organization [WHO] stage I or II and CD4 counts > 350 cells/mm3) were circumcised in two separate but procedurally identical trials of MC for HIV and/or sexually transmitted infection prevention in rural Rakai, Uganda. Participants were followed at 1–2 d and 5–9 d, and at 4–6 wk, to assess surgery-related AEs, wound healing, and resumption of intercourse. AE risks and wound healing were compared in HIV-positive and HIV-negative men. Adjusted odds ratios (AdjORs) were estimated by multiple logistic regression, adjusting for baseline characteristics and postoperative resumption of sex. At enrollment, HIV-positive men were older, more likely to be married, reported more sexual partners, less condom use, and higher rates of sexually transmitted disease symptoms than HIV-negative men. Risks of moderate or severe AEs were 3.1/100 and 3.5/100 in HIV-positive and HIV-negative participants, respectively (AdjOR 0.91, 95% confidence interval [CI] 0.47–1.74). Infections were the most common AEs (2.6/100 in HIV-positive versus 3.0/100 in HIV-negative men). Risks of other complications were similar in the two groups. The proportion with completed healing by 6 wk postsurgery was 92.7% in HIV-positive men and 95.8% in HIV-negative men (p = 0.007). AEs were more common in men who resumed intercourse before wound healing compared to those who waited (AdjOR 1.56, 95% CI 1.05–2.33).
Conclusions
Overall, the safety of MC was comparable in asymptomatic HIV-positive and HIV-negative men, although healing was somewhat slower among the HIV infected. All men should be strongly counseled to refrain from intercourse until full wound healing is achieved.
Trial registration: http://www.ClinicalTrials.gov; for HIV-negative men, #NCT00047073 and for HIV-positive men, #NCT00047073.
Ron Gray and colleagues report on complications of circumcision in HIV-infected and HIV-uninfected men from two related trials in Uganda, finding increased risk with intercourse before wound healing.
Editors' Summary
Background
Worldwide over 33 million people are thought to be living with HIV, and in the absence of a vaccine, preventing its spread is a major health issue. The World Health Organization (WHO) and the Joint United Nations Programme on HIV/AIDS (UNAIDS) estimate that 68% of 2.5 million new infections worldwide in 2007 took place in sub-Saharan Africa, where 76% of 2.1 million AIDS-related deaths also took place.
One of the principal means of person-to-person transmission of HIV is through sex without the protection of a condom. In parts of Africa, male circumcision is performed in infancy or childhood for religious or cultural reasons or is a traditional rite of passage that marks the transition from child to man. Three trials, in South Africa, Kenya, and Uganda, each found that circumcised men were around half as likely as uncircumcised men to contract HIV from HIV-positive female partners. After reviewing the results, WHO and UNAIDS issued joint advice that male circumcision should be promoted for preventing HIV infection in heterosexual men. As male circumcision does not provide complete protection against HIV infection, they advised that it should be promoted in addition to existing strategies of promoting condom use, abstinence, and a reduction in the number of sexual partners.
Why Was This Study Done?
Although earlier studies had shown that adult male circumcision, when performed in Africa under optimal conditions, is a safe procedure for HIV-negative men, it was not known whether it would also be a safe procedure for HIV-positive men. WHO guidelines recommend that HIV-positive men who request the procedure or have a medical need and no contraindications for it should be circumcised. Also, exclusion of HIV-positive men from circumcision programs may result in stigmatization of these men, and discourage participation by men who do not wish to be tested for HIV. Therefore, it is important to know whether the procedure is safe for HIV-positive men.
What Did the Researchers Do and Find?
The authors compared results from two separate clinical trials carried out with identical procedures in rural Rakai, Uganda. The first, which compared the effect of circumcision with no circumcision in HIV-negative men, was one of the three trials that persuaded the WHO and UNAIDS to promote male circumcision as an HIV prevention strategy. The second Rakai trial did the same comparison but in men who were HIV positive and without symptoms. In this present study, the authors used data from both trials to compare the likelihood of surgery-related complications following circumcision for HIV-negative and HIV-positive men.
The trials recruited men aged 15–49, who were randomly assigned to be circumcised either on enrollment or two years later and were followed up to monitor complications related to the procedure, such as infections, as well as wound healing and when the participant first had sex after the operation. Condom use was recorded at enrollment and six months after enrollment.
The researchers found that most complications were infrequent, mild, and comparable in both groups, with moderate-to-severe complications occurring in only 3%–4% of men in each group. However, delayed wound healing was more frequent in HIV-positive men. Complications were more likely among men who had sex before healing was complete; such men were more likely to be HIV-positive and/or married. Similarly, moderate or severe complications were more likely where men had symptoms of sexually transmitted disease at enrollment, although these were treated before surgery, and these men were more likely to be HIV-positive. Six months after enrollment, similar proportions of HIV-positive and HIV-negative men used condoms consistently, but HIV-positive men were more likely to report using condoms inconsistently than HIV-negative men. However, consistent use of a condom increased among the HIV-positive men compared to when they enrolled.
What Do these Findings Mean?
Circumcision in HIV-positive men without symptoms of AIDS has a low rate of complications, although healing is slower than in HIV-negative men. Because of the greater risk of complications if sex is resumed before full healing, both men and their women partners should be advised to have no sex for at least six weeks after the operation. A separately reported analysis from one of these studies found that women partners are more likely to become HIV infected by HIV-positive men who resume sex prior to complete wound healing. Therefore, for protection of both men and their female partners, it is essential to refrain from intercourse after circumcision until the wound has completely healed.
Because the study found no increased risk of surgical complications in HIV-positive men who undergo circumcision, it should not be necessary to screen men with no symptoms of HIV in future circumcision programs. This should reduce the complexity of implementing such programs and reduce any stigma resulting from exclusion, making it likely that more men will be willing to be circumcised. The rise in consistent condom use among HIV-positive men suggests that messages of safe sex are reaching an important target group and changing their behavior, and that circumcision does not make men less likely to use a condom.
The authors also noted that the rates of complications they observed were low compared with those following traditional circumcision procedures. Others have found that circumcision carried out under unsafe conditions has a high rate of complications. The authors of this study comment that the resources and standards of surgery during the trial represented best practice and that to attain similarly low rates of complications—and the confidence of men in the safety of the procedure—there is a need to ensure sufficient resources and high standards of training.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0050116.
WHO and the UNAIDS issued a joint report recommending male circumcision for HIV prevention and another on the HIV epidemic worldwide in December 2007
An information pack here on male circumcision and HIV prevention has also been developed jointly by WHO/UNAIDS, the United Nations International Children's Emergency Fund (UNICEF), the United Nations Population Fund (UNFPA), and the World Bank
The University of California San Francisco's HIV InSite provides information on HIV prevention, treatment, and policy
AEGIS is the world's largest searchable database on HIV and AIDS
The National AIDS Trust provides information on HIV prevention
doi:10.1371/journal.pmed.0050116
PMCID: PMC2408615  PMID: 18532873
5.  Intravaginal Practices, Bacterial Vaginosis, and HIV Infection in Women: Individual Participant Data Meta-analysis 
PLoS Medicine  2011;8(2):e1000416.
Pooling of data from 14,874 women in an individual participant data meta-analysis by Nicola Low and colleagues reveals that some intravaginal practices increase the risk of HIV acquisition.
Background
Identifying modifiable factors that increase women's vulnerability to HIV is a critical step in developing effective female-initiated prevention interventions. The primary objective of this study was to pool individual participant data from prospective longitudinal studies to investigate the association between intravaginal practices and acquisition of HIV infection among women in sub-Saharan Africa. Secondary objectives were to investigate associations between intravaginal practices and disrupted vaginal flora; and between disrupted vaginal flora and HIV acquisition.
Methods and Findings
We conducted a meta-analysis of individual participant data from 13 prospective cohort studies involving 14,874 women, of whom 791 acquired HIV infection during 21,218 woman years of follow-up. Data were pooled using random-effects meta-analysis. The level of between-study heterogeneity was low in all analyses (I2 values 0.0%–16.1%). Intravaginal use of cloth or paper (pooled adjusted hazard ratio [aHR] 1.47, 95% confidence interval [CI] 1.18–1.83), insertion of products to dry or tighten the vagina (aHR 1.31, 95% CI 1.00–1.71), and intravaginal cleaning with soap (aHR 1.24, 95% CI 1.01–1.53) remained associated with HIV acquisition after controlling for age, marital status, and number of sex partners in the past 3 months. Intravaginal cleaning with soap was also associated with the development of intermediate vaginal flora and bacterial vaginosis in women with normal vaginal flora at baseline (pooled adjusted odds ratio [OR] 1.24, 95% CI 1.04–1.47). Use of cloth or paper was not associated with the development of disrupted vaginal flora. Intermediate vaginal flora and bacterial vaginosis were each associated with HIV acquisition in multivariable models when measured at baseline (aHR 1.54 and 1.69, p<0.001) or at the visit before the estimated date of HIV infection (aHR 1.41 and 1.53, p<0.001), respectively.
Conclusions
This study provides evidence to suggest that some intravaginal practices increase the risk of HIV acquisition but a direct causal pathway linking intravaginal cleaning with soap, disruption of vaginal flora, and HIV acquisition has not yet been demonstrated. More consistency in the definition and measurement of specific intravaginal practices is warranted so that the effects of specific intravaginal practices and products can be further elucidated.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Since the first reported case of acquired immunodeficiency syndrome (AIDS) in 1981, the number of people infected with the human immunodeficiency virus (HIV), which causes AIDS, has risen steadily. By the end of 2009, an estimated 33.3 million people were living with HIV/AIDS. At the beginning of the epidemic, more men than women were infected with HIV but now, globally, more than half of all adults living with HIV/AIDS are women, and HIV/AIDS is the leading cause of death among women of child-bearing age. In sub-Saharan Africa, where more than two-thirds of HIV-positive people live, the situation for women is particularly bad. About 12 million women live with HIV/AIDS in this region compared with about 8 million men; among 15–24 year-olds, women are eight times more likely than men to be HIV-positive. This pattern of infection has developed because in sub-Saharan Africa most people contract HIV through heterosexual sex.
Why Was This Study Done?
If modifiable factors that increase women's vulnerability to HIV infection could be identified, it might be possible to develop effective female-initiated prevention interventions. Some experts think that intravaginal practices such as cleaning the vagina with soap or a cloth increase the risk of HIV infection by damaging the vagina's lining or by increasing bacterial vaginosis (a condition in which harmful bacteria disrupt the healthy vaginal flora) but the evidence for such an association is inconclusive. In this meta-analysis, the researchers pool individual participant data from several prospective longitudinal cohort studies to assess the association between intravaginal practices and HIV acquisition among women in sub-Saharan Africa. Meta-analysis is a statistical method that combines data from several studies to get a clearer view of the factors associated with of a disease than is possible from individual studies. In a prospective longitudinal cohort study, groups of participants with different baseline characteristics (here, women who did or did not use intravaginal practices), who do not have the outcome of interest at the start of the study (here, HIV infection) are followed to see whether these characteristics affect disease development.
What Did the Researchers Do and Find?
The researchers pooled individual participant data from 13 prospective cohort studies in sub-Saharan Africa involving nearly 15,000 women, 791 of whom acquired HIV, and asked whether HIV infection within 2 years of study enrollment was associated with self-reported intravaginal practices. That is, were women who used specific intravaginal practices more likely to become infected with HIV than women who did not use these practices? After controlling for age, marital status, and the number of recent sex partners, women who used cloth or paper to clean their vagina were nearly one and half times more likely to have acquired HIV infection as women who did not use this practice (a pooled adjusted hazard ratio [aHR] of 1.47). The insertion of products to dry or tighten the vagina and intravaginal cleaning with soap also increased women's chances of acquiring HIV (aHRs of 1.31 and 1.24, respectively). Moreover, intravaginal cleaning with soap was associated with the development of bacterial vaginosis, and disrupted vaginal flora and bacterial vaginosis were both associated with an increased risk of HIV acquisition.
What Do These Findings Mean?
These findings suggest that some intravaginal practices increase the risk of HIV acquisition but they do not prove that there is a causal link between any intravaginal practice, disruption of vaginal flora, and HIV acquisition. It could be that the women who use intravaginal practices share other unknown characteristics that affect their vulnerability to HIV infection. The accuracy of these findings is also likely to be affected by the use of self-reported data and inconsistent definitions of intravaginal practices. Nevertheless, given the widespread use of intravaginal practices in some sub-Saharan countries (95% of female sex workers in Kenya use such practices, for example), these findings suggest that encouraging women to use less harmful intravaginal practices (for example, washing with water alone) should be included in female-initiated HIV prevention research strategies in sub-Saharan Africa and other regions where intravaginal practices are common.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000416
The US National Institute of Allergy and Infectious Diseases provides information on HIV infection and AIDS and on bacterial vaginosis
The US Centers for Disease Control and Prevention has information on all aspects of HIV/AIDS, including specific information about HIV/AIDS and women; it also has information on bacterial vaginosis (in English and Spanish)
HIV InSite has information on all aspects of HIV/AIDS
Information is available from Avert, an international AIDS nonprofit on all aspects of HIV/AIDS, including HIV/AIDS and women and HIV/AIDS in Africa (in English and Spanish)
A full description of the researchers' study protocol is available
Several Web sites provide information on microbicides Global Campaign for Microbicides, Microbicides Development Programme, Microbicides Trials Network, and International Partnership for Microbicides
doi:10.1371/journal.pmed.1000416
PMCID: PMC3039685  PMID: 21358808
6.  A Population-Based Study on Alcohol and High-Risk Sexual Behaviors in Botswana 
PLoS Medicine  2006;3(10):e392.
Background
In Botswana, an estimated 24% of adults ages 15–49 years are infected with HIV. While alcohol use is strongly associated with HIV infection in Africa, few population-based studies have characterized the association of alcohol use with specific high-risk sexual behaviors.
Methods and Findings
We conducted a cross-sectional, population-based study of 1,268 adults from five districts in Botswana using a stratified two-stage probability sample design. Multivariate logistic regression was used to assess correlates of heavy alcohol consumption (>14 drinks/week for women, and >21 drinks/week for men) as a dependent variable. We also assessed gender-specific associations between alcohol use as a primary independent variable (categorized as none, moderate, problem and heavy drinking) and several risky sex outcomes including: (a) having unprotected sex with a nonmonogamous partner; (b) having multiple sexual partners; and (c) paying for or selling sex in exchange for money or other resources. Criteria for heavy drinking were met by 31% of men and 17% of women. Adjusted correlates of heavy alcohol use included male gender, intergenerational relationships (age gap ≥10 y), higher education, and living with a sexual partner. Among men, heavy alcohol use was associated with higher odds of all risky sex outcomes examined, including unprotected sex (AOR = 3.48; 95% confidence interval [CI], 1.65 to 7.32), multiple partners (AOR = 3.08; 95% CI, 1.95 to 4.87), and paying for sex (AOR = 3.65; 95% CI, 2.58 to 12.37). Similarly, among women, heavy alcohol consumption was associated with higher odds of unprotected sex (AOR = 3.28; 95% CI, 1.71 to 6.28), multiple partners (AOR = 3.05; 95% CI, 1.83 to 5.07), and selling sex (AOR = 8.50; 95% CI, 3.41 to 21.18). A dose-response relationship was seen between alcohol use and risky sexual behaviors, with moderate drinkers at lower risk than both problem and heavy drinkers.
Conclusions
Alcohol use is associated with multiple risks for HIV transmission among both men and women. The findings of this study underscore the need to integrate alcohol abuse and HIV prevention efforts in Botswana and elsewhere.
Alcohol use is associated with multiple risks for HIV transmission in men and women. The findings underscore the need to integrate alcohol abuse and HIV prevention efforts in Botswana and elsewhere.
Editors' Summary
Background.
Human immunodeficiency virus (HIV), the cause of acquired immunodeficiency syndrome (AIDS), is most commonly spread through unprotected sex with an infected partner. HIV enters the body through the lining of the sex organs, rectum, or mouth, and destroys immune system cells, leaving the infected person susceptible to other viruses and bacteria. Although HIV education and prevention campaigns emphasize the importance of safe sex in reducing HIV transmission, people continue to become infected by having unprotected sex (that is, not using a condom) with either a nonmonogamous partner or multiple sexual partners, or in situations where they are paying for or selling sex. Research in different populations suggested that heavy alcohol use is associated with risky sexual behaviors. This is because alcohol relaxes the brain and body, reduces inhibitions, and diminishes risk perception. Drinking alcohol may further increase the risk of becoming infected with HIV through its suppressive effects on the immune system.
Why Was This Study Done?
Alcohol abuse is widespread in sub-Saharan Africa where most HIV infections occur and has been associated with risky sexual behaviors. It may therefore be one of the most common, potentially modifiable HIV risk factors in this region. However, research to date has concentrated on the association between alcohol consumption and risky sex in people attending HIV-treatment clinics or recruited at beer halls, and these populations may not be representative of the general population of sub-Saharan Africa. In this study, the researchers have investigated the potential role of alcohol in perpetuating the HIV epidemic by undertaking a population-based study on alcohol use and high-risk sexual behaviors in Botswana. Nearly a quarter of adults are infected with HIV here, and alcohol abuse is also common, particularly in the townships.
What Did the Researchers Do and Find?
The researchers recruited a random cross-section of people from the five districts of Botswana with the highest number of HIV-infected individuals and interviewed all 1,268 participants using a questionnaire. This included general questions about the participants (for example, their age and marital status) and questions about alcohol use, sexual behavior, and knowledge of HIV. Overall, 31% of the men in the study and 17% of the women were heavy drinkers—more than 21 drinks/week for men, 14 for women; a drink is half a pint of beer or a glass of wine. Heavy alcohol use was associated with being male, being in an intergenerational relationship (at least 10 years age difference between partners; intergenerational sex facilitates the continued spread of HIV in sub-Saharan Africa), having had more education, and living with a sexual partner. Among men, those who drank heavily were three to four times more likely to have unprotected sex or multiple partners or to pay for sex than nondrinkers. Among women, there was a similar association between heavy drinking and having unprotected sex or multiple partners, and heavy drinkers were eight times as likely to sell sex as nondrinkers. For both men and women, the more they drank, the more likely they were to have risky sex. The study did not address behavior among same-sex partnerships.
What Do These Findings Mean?
This study indicates that heavy alcohol consumption is strongly and consistently associated with sexual risk behaviors in both men and women in Botswana. Because of the study design, it does not prove that heavy alcohol use is the cause of such behaviors but provides strong circumstantial evidence that this is the case. It is possible that these results may not apply to neighboring African countries—Botswana is unique in being relatively wealthy and in its government being strongly committed to tackling HIV. Nevertheless, taken together with the results of other studies, this research strongly argues for the need to deal with alcohol abuse within HIV prevention programs in sub-Saharan Africa. Strategies to do this could include education campaigns that target both alcohol use and HIV in schools and in social venues, including beer halls. But, stress the researchers, any strategy that is used must consider the cultural and social significance of alcohol use (in Botswana, alcohol use is a symbol of masculinity and high socioeconomic status) and must simultaneously tackle not only the overlap between alcohol use and risky sexual behavior but also the overlap between alcohol and other risk behaviors such as intergenerational sex.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0030392.
US National Institute of Allergy and Infectious Diseases factsheet on HIV infection and AIDS
US Department of Health and Human Services information on AIDS
US Centers for Disease Control and Prevention information on HIV/AIDS
US National Institute on Alcohol Abuse and Alcoholism patient information on alcohol and HIV/AIDS]
Aidsmap, information on HIV and AIDS provided by the charity NAM,which includes some information on HIV infections and alcohol
AVERT information on HIV and AIDS in Botswana
doi:10.1371/journal.pmed.0030392
PMCID: PMC1592342  PMID: 17032060
7.  Hormonal Contraception and the Risk of HIV Acquisition: An Individual Participant Data Meta-analysis 
PLoS Medicine  2015;12(1):e1001778.
In a meta-analysis of individual participant data, Charles Morrison and colleagues explore the association between hormonal contraception use and risk of HIV infection in sub-Saharan Africa.
Background
Observational studies of a putative association between hormonal contraception (HC) and HIV acquisition have produced conflicting results. We conducted an individual participant data (IPD) meta-analysis of studies from sub-Saharan Africa to compare the incidence of HIV infection in women using combined oral contraceptives (COCs) or the injectable progestins depot-medroxyprogesterone acetate (DMPA) or norethisterone enanthate (NET-EN) with women not using HC.
Methods and Findings
Eligible studies measured HC exposure and incident HIV infection prospectively using standardized measures, enrolled women aged 15–49 y, recorded ≥15 incident HIV infections, and measured prespecified covariates. Our primary analysis estimated the adjusted hazard ratio (aHR) using two-stage random effects meta-analysis, controlling for region, marital status, age, number of sex partners, and condom use. We included 18 studies, including 37,124 women (43,613 woman-years) and 1,830 incident HIV infections. Relative to no HC use, the aHR for HIV acquisition was 1.50 (95% CI 1.24–1.83) for DMPA use, 1.24 (95% CI 0.84–1.82) for NET-EN use, and 1.03 (95% CI 0.88–1.20) for COC use. Between-study heterogeneity was mild (I2 < 50%). DMPA use was associated with increased HIV acquisition compared with COC use (aHR 1.43, 95% CI 1.23–1.67) and NET-EN use (aHR 1.32, 95% CI 1.08–1.61). Effect estimates were attenuated for studies at lower risk of methodological bias (compared with no HC use, aHR for DMPA use 1.22, 95% CI 0.99–1.50; for NET-EN use 0.67, 95% CI 0.47–0.96; and for COC use 0.91, 95% CI 0.73–1.41) compared to those at higher risk of bias (pinteraction = 0.003). Neither age nor herpes simplex virus type 2 infection status modified the HC–HIV relationship.
Conclusions
This IPD meta-analysis found no evidence that COC or NET-EN use increases women’s risk of HIV but adds to the evidence that DMPA may increase HIV risk, underscoring the need for additional safe and effective contraceptive options for women at high HIV risk. A randomized controlled trial would provide more definitive evidence about the effects of hormonal contraception, particularly DMPA, on HIV risk.
Editors’ Summary
Background
AIDS has killed about 36 million people since the first recorded case of the disease in 1981. About 35 million people (including 25 million living in sub-Saharan Africa) are currently infected with HIV, the virus that causes AIDS, and every year, another 2.3 million people become newly infected with HIV. At the beginning of the epidemic, more men than women were infected with HIV. Now, about half of all adults infected with HIV are women. In 2013, almost 60% of all new HIV infections among young people aged 15–24 years occurred among women, and it is estimated that, worldwide, 50 young women are newly infected with HIV every hour. Most women become infected with HIV through unprotected intercourse with an infected male partner—biologically, women are twice as likely to become infected through unprotected intercourse as men. A woman’s risk of becoming infected with HIV can be reduced by abstaining from sex, by having one or a few partners, and by always using condoms.
Why Was This Study Done?
Women and societies both benefit from effective contraception. When contraception is available, women can avoid unintended pregnancies, fewer women and babies die during pregnancy and childbirth, and maternal and infant health improves. However, some (but not all) observational studies (investigations that measure associations between the characteristics of participants and their subsequent development of specific diseases) have reported an association between hormonal contraceptive use and an increased risk of HIV acquisition by women. So, does hormonal contraception increase the risk of HIV acquisition among women or not? Here, to investigate this question, the researchers undertake an individual participant data meta-analysis of studies conducted in sub-Saharan Africa (a region where both HIV infection and unintended pregnancies are common) to compare the incidence of HIV infection (the number of new cases in a population during a given time period) among women using and not using hormonal contraception. Meta-analysis is a statistical method that combines the results of several studies; an individual participant data meta-analysis combines the data recorded for each individual involved in the studies rather than the aggregated results from each study.
What Did the Researchers Do and Find?
The researchers included 18 studies that measured hormonal contraceptive use and incident HIV infection among women aged 15–49 years living in sub-Saharan Africa in their meta-analysis. More than 37,000 women took part in these studies, and 1,830 became newly infected with HIV. Half of the women were not using hormonal contraception, a quarter were using depot-medroxyprogesterone acetate (DMPA; an injectable hormonal contraceptive), and the remainder were using combined oral contraceptives (COCs) or norethisterone enanthate (NET-EN, another injectable contraceptive). After adjustment for other factors likely to influence HIV acquisition (for example, condom use), women using DMPA had a 1.5-fold increased risk of HIV acquisition compared to women not using hormonal contraception. There was a slightly increased risk of HIV acquisition among women using NET-EN compared to women not using hormonal contraception, but this increase was not statistically significant (it may have happened by chance alone). There was no increased risk of HIV acquisition associated with COC use. DMPA use was associated with a 1.43-fold and 1.32-fold increased risk of HIV acquisition compared with COC and NET-EN use, respectively. Finally, neither age nor herpes simplex virus 2 infection status modified the effect of hormonal contraceptive use on HIV acquisition.
What Do These Findings Mean?
The findings of this individual patient data meta-analysis provide no evidence that COC or NET-EN use increases a woman’s risk of acquiring HIV, but add to the evidence suggesting that DMPA use increases the risk of HIV acquisition. These findings are likely to be more accurate than those of previous meta-analyses that used aggregated data but are likely to be limited by the quality, design, and representativeness of the studies included in the analysis. These findings nevertheless highlight the need to develop additional safe and effective contraceptive options for women at risk of HIV, particularly those living in sub-Saharan Africa, where although contraceptive use is generally low, DMPA is the most widely used hormonal contraceptive. In addition, these findings highlight the need to initiate randomized controlled trials to provide more definitive evidence of the effects of hormonal contraception, particularly DMPA, on HIV risk.
Additional Information.
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001778.
Information is available from the US National Institute of Allergy and Infectious Diseases on HIV infection and AIDS
NAM/aidsmap provides basic information about HIV/AIDS, and summaries of recent research findings on HIV care and treatment, including personal stories about living with HIV/AIDS and a news report on this meta-analysis
Information is available from Avert, an international AIDS charity, on many aspects of HIV/AIDS, including detailed information on women, HIV, and AIDS, and on HIV and AIDS in South Africa (in English and Spanish); personal stories of women living with HIV are available
The World Health Organization provides information on all aspects of HIV/AIDS (in several languages); information about a 2012 WHO technical consultation about hormonal contraception and HIV
The 2013 UNAIDS World AIDS Day report provides up-to-date information about the AIDS epidemic and efforts to halt it; UNAIDS also provides information about HIV and hormonal contraception
doi:10.1371/journal.pmed.1001778
PMCID: PMC4303292  PMID: 25612136
8.  Association of the ANRS-12126 Male Circumcision Project with HIV Levels among Men in a South African Township: Evaluation of Effectiveness using Cross-sectional Surveys 
PLoS Medicine  2013;10(9):e1001509.
Betran Auvert and colleagues report findings from the Bophelo Pele project, a community-based HIV prevention intervention offering free voluntary medical male circumcision (VMMC), that demonstrate an association between VMMC roll-out and a reduction in the incidence and prevalence of HIV in the community.
Please see later in the article for the Editors' Summary
Background
Randomized controlled trials have shown that voluntary medical male circumcision (VMMC) reduces HIV infection by 50% to 60% in sub-Saharan African populations; however, little is known about the population-level effect of adult male circumcision (MC) as an HIV prevention method. We assessed the effectiveness of VMMC roll-out on the levels of HIV in the South African township of Orange Farm where the first randomized controlled trial (RCT) to test the effect of VMMC on HIV acquisition was conducted in 2002–2005.
Methods and Findings
The Bophelo Pele project is a community-based campaign against HIV, which includes the roll-out of free VMMC. A baseline cross-sectional biomedical survey was conducted in 2007–2008 among a random sample of 1,998 men aged 15 to 49 (survey response rate 80.7%). In 2010–2011, we conducted a follow-up random survey among 3,338 men aged 15 to 49 (survey response rate 79.6%) to evaluate the project. Participants were interviewed, blood samples were collected and tested for HIV and recent HIV infection (using the BED HIV incidence assay), and MC status was assessed through a clinical examination. Data were analyzed using multivariate and propensity statistical methods.
Owing to the VMMCs performed in the context of the RCT and the Bophelo Pele project, the prevalence rate of adult MC increased from 0.12 (95% CI 0.10–0.14) to 0.53 (95% CI 0.51–0.55). Without these VMMCs, the HIV prevalence rate in 2010–2011 would have been 19% (95% CI 12%–26%) higher (0.147 instead of 0.123).
When comparing circumcised and uncircumcised men, no association of MC status with sexual behavior was detected. Among circumcised and uncircumcised men, the proportion consistently using condoms with non-spousal partners in the past 12 months was 44.0% (95% CI 41.7%–46.5%) versus 45.4% (95% CI 42.2%–48.6%) with weighted prevalence rate ratio (wPRR) = 0.94 (95% CI 0.85–1.03). The proportion having two or more non-spousal partners was 50.4% (95% CI 47.9%–52.9%) versus 44.2% (95% CI 41.3%–46.9%) with wPRR = 1.03 (95% CI 0.95–1.10).
We found a reduction of BED-estimated HIV incidence rate ranging from 57% (95% CI 29%–76%) to 61% (95% CI 14%–83%) among circumcised men in comparison with uncircumcised men.
Conclusions
Findings suggest that the roll-out of VMMC in Orange Farm is associated with a significant reduction of HIV levels in the community. The main limitation of the study is that it was not randomized and cannot prove a causal association. The roll-out of VMMC among adults in sub-Saharan Africa should be an international priority and needs to be accelerated to effectively combat the spread of HIV.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Every year about 2.2 million people (mostly in sub-Saharan Africa) become infected with HIV, the virus that causes AIDS. There is no cure for HIV/AIDS. Consequently, prevention of HIV transmission is extremely important. Because HIV is most often spread through unprotected sex with an infected partner, individuals can reduce their risk of HIV infection by abstaining from sex, by having only one or a few sexual partners, and by always using a male or female condom. The results of three randomized controlled trials conducted in sub-Saharan Africa also suggest that voluntary medical male circumcision (VMMC)—the removal of the foreskin, a loose fold of skin that covers the head of the penis—can reduce the heterosexual acquisition of HIV in men by 50%–60%. In 2007, the World Health Organization (WHO) and the Joint United Nations Programme on HIV/AIDS (UNAIDS) recommended that VMMC should be offered as part of comprehensive HIV risk reduction programs in settings with generalized HIV epidemics and low levels of male circumcision and prioritized 14 east and southern African countries for VMMC roll-out.
Why Was This Study Done?
To date, about 3 million VMMCs have been performed for HIV prevention but it is not known whether “real world” VMMC roll-out programs will replicate the promising results obtained in the earlier trials. Indeed, there are fears that “risk compensation” (an increase in risky sexual behaviors after VMMC) might lead to increased HIV transmission in regions where VMMC is rolled out. In this study, the researchers use sequential cross-sectional surveys (studies that collect data from a group of people at a single time point) to investigate HIV infection levels in men in Orange Farm, a township in South Africa where one of the randomized controlled trials of VMMC was undertaken. The surveys were conducted before and after implementation of the Bophelo Pele project, a community-based campaign against HIV that was initiated in 2008 and that includes free VMMC.
What Did the Researchers Do and Find?
The researchers asked a random sample of nearly 2,000 men aged 15–49 years about their sexual behavior (for example, how many non-spousal partners they had had over the past year), and their intention to become circumcised if uncircumcised in a baseline survey in 2007–2008. The study participants were also offered HIV counseling and testing (including a test that indicated whether the participant had recently become HIV positive) and were examined to see whether they were already circumcised. A similar follow-up survey was conducted in 2010–2011 in which more than 3,000 men were invited to take part. At baseline, 12% of the men surveyed had been circumcised (a prevalence of circumcision of 12%) whereas in the follow-up survey, the overall prevalence of circumcision and the prevalence of circumcision among 15–29 year-olds (an important target group for VMMC roll-out) were 53% and 58%, respectively. The overall HIV prevalence at follow-up was 12% and the researchers estimated that without the VMMCs performed during the Bophelo Pele project and the preceding randomized control trial the prevalence of HIV among men living in Orange Farm would have been 15% in 2011. Using various cut-off values and corrections for a laboratory-based test to measure recent HIV infections, the researchers reported a reduction in the rate of new HIV infections (incidence rate) ranging from 57% to 61% among circumcised men in comparison with uncircumcised men. Importantly, there was no evidence of an association between circumcision status and risky sexual behavior but circumcision was associated with a reduction in the number of men who had recently become HIV positive.
What Do These Findings Mean?
These findings suggest that VMMC roll out in Orange Farm is associated with a reduction in HIV infection levels in the community and that circumcision is not associated with changes in sexual behavior that might affect HIV infection rates. They also suggest that VMMC roll-out is associated with a rapid uptake of VMMC, especially among young men, in an African community where male circumcision is not a social norm. Because this study is not a randomized controlled trial, it cannot establish cause and effect. Thus, although the observed reduction in HIV prevalence among circumcised men compared to uncircumcised men suggests that circumcision provided protection against HIV acquisition within the study population, the results do not conclusively prove this. The findings of this study nevertheless support the continuation and acceleration of the roll-out of adult VMMC in Africa although further studies are needed to show whether VMMC roll-out is also associated with a reduction in HIV acquisition among women and among uncircumcised men.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001509.
Information and resources on male circumcision for HIV prevention are available
Information is available from the US National Institute of Allergy and infectious diseases on HIV infection and AIDS
NAM/aidsmap provides basic information about HIV/AIDS, summaries of recent research findings on HIV care and treatment, and information on male circumcision for the prevention of HIV transmission
Information is available from WHO and UNAIDS on all aspects of HIV/AIDS; the Clearinghouse on Male Circumcision, a resource provided by WHO, UNAIDS and other international bodies, provides information and tools for VMMC policy development and program implementation; a report entitled Progress in scaling up voluntary medical male circumcision for HIV prevention in East and Southern Africa, January-December 2011 is available
Information is available from Avert, an international AIDS charity on many aspects of HIV/AIDS, including information on HIV and AIDS in South Africa, on HIV prevention, and on circumcision and HIV (in English and Spanish)
A 2010 PLOS Medicine Research Article by Pascale Lissouba et al. provides more information about the Bophelo Pele project
Personal stories about living with HIV/AIDS are available through Avert, through Nam/aidsmap, and through the charity website Healthtalkonline; a personal story about circumcision in Zimbabwe is available
doi:10.1371/journal.pmed.1001509
PMCID: PMC3760784  PMID: 24019763
9.  Intermittent Intravaginal Antibiotic Treatment of Bacterial Vaginosis in HIV-Uninfected and -Infected Women: A Randomized Clinical Trial 
PLoS Clinical Trials  2007;2(2):e10.
Objective:
Assess efficacy of intermittent intravaginal metronidazole gel treatment in reducing frequency of bacterial vaginosis (BV).
Design:
Randomized, double-masked, placebo-controlled phase 3 trial.
Setting:
Postnatal and family planning clinics of the Queen Elizabeth Central Hospital and two health centers in Blantyre, Malawi.
Participants:
Nonpregnant HIV-uninfected and -infected women.
Intervention:
Intravaginal metronidazole treatment and placebo gels provided at baseline and every 3 mo for 1 y.
Outcome measures:
Primary: Cross-sectional and longitudinal comparisons of BV frequency at baseline, 1 mo after product dispensation (post-treatment evaluation [PTE]), and every quarterly visit. Secondary: Effect of treatment on BV clearance and recurrence.
Results:
Baseline: 842 HIV-uninfected and 844 HIV-infected women were enrolled. The frequency of BV at baseline in treatment and placebo arms, respectively, was 45.9% and 46.8% among HIV-uninfected women, and 60.5% and 56.9% among HIV-infected women. Primary outcomes: At the PTEs the prevalence of BV was consistently lower in treatment than placebo arms irrespective of HIV status. The differences were statistically significant mainly in HIV-uninfected women. Prevalence of BV was also reduced over time in both treatment and placebo arms. In a multivariable analysis that controlled for other covariates, the effect of intravaginal metronidazole treatment gel compared with placebo was not substantial: adjusted relative risk (RR) 0.90, 95% confidence interval (CI) 0.83–0.97 in HIV-uninfected women and adjusted RR 0.95, 95% CI 0.89–1.01 in HIV-infected women. Secondary outcomes: Intravaginal metronidazole treatment gel significantly increased BV clearance (adjusted hazard ratio [HR] 1.34, 95% CI 1.07–1.67 among HIV-uninfected women and adjusted HR 1.29, 95% CI 1.06–1.58 among HIV-infected women) but was not associated with decreased BV recurrence. Safety: No serious adverse events were related to use of intravaginal gels.
Conclusion:
Intermittent microbicide treatment with intravaginal gels is an innovative approach that can reduce the frequency of vaginal infections such as BV.
Editorial Commentary
Background: Bacterial vaginosis (BV) results from a change in the normal balance of bacteria in the vaginal tract, and is very common. In pregnant women, it is associated with poorer outcomes in pregnancy, and is also linked with HIV transmission (although it is not certain that BV actually increases the chance of getting HIV—just because these two occur together it does not necessarily follow that one causes the other). BV can be treated with metronidazole tablets, although these can cause gut symptoms and should not be taken repeatedly. The researchers wanted to carry out a multiclinic–based trial to find out whether a metronidazole gel applied intermittently to the vagina (for five nights every three months) would reduce the frequency of BV among women in Malawi. HIV-infected and HIV-uninfected women, recruited from postnatal and family planning clinics, were randomized to receive either metronidazole gels, or equivalent placebo gels, every three months and were then followed up for 12 months. The primary outcome for the trial was the proportion of women with BV at each quarterly follow-up visit, and the researchers intended to compare this outcome between treatment arms at each visit and also to look at the overall changes over time among women receiving either metronidazole or placebo, looking separately at HIV-infected and HIV-uninfected women.
What this trial shows: In total 1,686 women took part in the trial (842 not infected with HIV, and 844 infected with HIV). The proportion of HIV-uninfected women with BV dropped by around 20% over the course of the trial, both in women using metronidazole and in those using placebo. However, when comparing the proportion of HIV-uninfected women with BV between the two arms of the trial, there did not seem to be a consistent effect: differences were statistically significant at some time points and not others. Among HIV-infected women, there was also a drop over the course of the trial in the proportion of women with BV, irrespective of whether they used metronidazole or placebo. Again, when comparing the rate of BV among HIV-infected women between study arms (metronidazole versus placebo), the researchers did not see a consistent trend; differences were statistically significant at some time points but not others. Overall, when comparing metronidazole and placebo in an analysis that controlled for other factors, the metronidazole gel seemed to show a small effect in reduction of BV among HIV-uninfected women, but no obvious effect among HIV-infected women.
Strengths and limitations: Strengths in the design of this trial include the sample size, which was appropriate to detect an important effect of the metronidazole gel (versus placebo) had one existed, and the randomization and blinding procedures, which were designed to minimize the chance that the trialists or women being enrolled could anticipate to which arm of the trial they might be assigned. A key limitation of this study, as the researchers acknowledge, is the absence of a “no treatment” study arm. The frequency of BV dropped over the course of the trial in women using the placebo gel, raising the possibility that the placebo actually has some effect on bacteria in the vagina. However, a trial with a “no treatment” arm would pose its own problems, since trialists and participants would then not be fully blinded as to their treatment status.
Contribution to the evidence: This trial adds data on the efficacy of metronidazole gel when used intermittently, and among women in the community who may or may not actually have BV. Previous studies have evaluated treatment with metronidazole among women who already have symptoms or a diagnosis of BV. The findings of this trial rule out a substantial effect of metronidazole gel, as compared to placebo gel, in reducing the frequency of BV in this setting.
doi:10.1371/journal.pctr.0020010
PMCID: PMC1851729  PMID: 17318258
10.  Incident HIV during Pregnancy and Postpartum and Risk of Mother-to-Child HIV Transmission: A Systematic Review and Meta-Analysis 
PLoS Medicine  2014;11(2):e1001608.
Alison Drake and colleagues conduct a systematic review and meta-analysis to estimate maternal HIV incidence during pregnancy and the postpartum period and to compare mother-to-child HIV transmission risk among women with incident versus chronic infection.
Please see later in the article for the Editors' Summary
Background
Women may have persistent risk of HIV acquisition during pregnancy and postpartum. Estimating risk of HIV during these periods is important to inform optimal prevention approaches. We performed a systematic review and meta-analysis to estimate maternal HIV incidence during pregnancy/postpartum and to compare mother-to-child HIV transmission (MTCT) risk among women with incident versus chronic infection.
Methods and Findings
We searched PubMed, Embase, and AIDS-related conference abstracts between January 1, 1980, and October 31, 2013, for articles and abstracts describing HIV acquisition during pregnancy/postpartum. The inclusion criterion was studies with data on recent HIV during pregnancy/postpartum. Random effects models were constructed to pool HIV incidence rates, cumulative HIV incidence, hazard ratios (HRs), or odds ratios (ORs) summarizing the association between pregnancy/postpartum status and HIV incidence, and MTCT risk and rates. Overall, 1,176 studies met the search criteria, of which 78 met the inclusion criterion, and 47 contributed data. Using data from 19 cohorts representing 22,803 total person-years, the pooled HIV incidence rate during pregnancy/postpartum was 3.8/100 person-years (95% CI 3.0–4.6): 4.7/100 person-years during pregnancy and 2.9/100 person-years postpartum (p = 0.18). Pooled cumulative HIV incidence was significantly higher in African than non-African countries (3.6% versus 0.3%, respectively; p<0.001). Risk of HIV was not significantly higher among pregnant (HR 1.3, 95% CI 0.5–2.1) or postpartum women (HR 1.1, 95% CI 0.6–1.6) than among non-pregnant/non-postpartum women in five studies with available data. In African cohorts, MTCT risk was significantly higher among women with incident versus chronic HIV infection in the postpartum period (OR 2.9, 95% CI 2.2–3.9) or in pregnancy/postpartum periods combined (OR 2.3, 95% CI 1.2–4.4). However, the small number of studies limited power to detect associations and sources of heterogeneity.
Conclusions
Pregnancy and the postpartum period are times of persistent HIV risk, at rates similar to “high risk” cohorts. MTCT risk was elevated among women with incident infections. Detection and prevention of incident HIV in pregnancy/postpartum should be prioritized, and is critical to decrease MTCT.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Worldwide, about 3.4 million children younger than 15 years old (mostly living in sub-Saharan Africa) are infected with HIV, the virus that causes AIDS by gradually destroying immune system cells, thereby leaving infected individuals susceptible to other serious infections. In 2012 alone, 230,000 children (more than 700 every day) were newly infected with HIV. Most HIV infections among children are the result of mother-to-child HIV transmission (MTCT) during pregnancy, delivery, or breastfeeding. The rate of MTCT (and deaths among HIV-positive pregnant women from complications related to HIV infection) can be greatly reduced by testing women for HIV infection during pregnancy (antenatal HIV testing), treating HIV-positive women with antiretroviral drugs (ARVs, powerful drugs that control HIV replication and allow the immune system to recover) during pregnancy, delivery, and breastfeeding, and giving ARVs to their newborn babies.
Why Was This Study Done?
The World Health Organization and the Joint United Nations Programme on HIV/AIDS (UNAIDS) have developed a global plan that aims to move towards eliminating new HIV infections among children by 2015 and towards keeping their mothers alive. To ensure the plan's success, the incidence of HIV (the number of new infections) among women and the rate of MTCT must be reduced by increasing ARV uptake by mothers and their infants for the prevention of MTCT. However, the risk of HIV infection among pregnant women and among women who have recently given birth (postpartum women) is poorly understood because, although guidelines recommend repeat HIV testing during late pregnancy or at delivery in settings where HIV infection is common, pregnant women are often tested only once for HIV infection. The lack of retesting represents a missed opportunity to identify pregnant and postpartum women who have recently acquired HIV and to prevent MTCT by initiating ARV therapy. In this systematic review (a study that uses predefined criteria to identify all the research on a given topic) and meta-analysis (a study that uses statistical methods to combine the results of several studies), the researchers estimate maternal HIV incidence during pregnancy and the postpartum period, and compare the risk of MTCT among women with incident (new) and chronic (long-standing) HIV infection.
What Did the Researchers Do and Find?
The researchers identified 47 studies (35 undertaken in Africa) that examined recent HIV acquisition by women during pregnancy and the 12-month postpartum period. They used random effects statistical models to estimate the pooled HIV incidence rate and cumulative HIV incidence (the number of new infections per number of people at risk), and the association between pregnancy/postpartum status and HIV incidence and MTCT risk and rates. The pooled HIV incidence rate among pregnant/postpartum women estimated from 19 studies (all from sub-Saharan Africa) that reported HIV incidence rates was 3.8/100 person-years. The pooled cumulative HIV incidence was significantly higher in African countries than in non-African countries (3.6% and 0.3%, respectively; a “significant” difference is one that is unlikely to arise by chance). In the five studies that provided suitable data, the risk of HIV acquisition was similar in pregnant, postpartum, and non-pregnant/non-postpartum women. Finally, among African women, the risk of MTCT was 2.9-fold higher during the postpartum period among those who had recently acquired HIV than among those with chronic HIV infection, and 2.3-fold higher during the pregnancy/postpartum periods combined.
What Do These Findings Mean?
These results suggest that women living in regions where HIV infection is common are at high risk of acquiring HIV infection during pregnancy and the postpartum period and that mothers who acquire HIV during pregnancy or postpartum are more likely to pass the infection on to their offspring than mothers with chronic HIV infections. However, the small number of studies included in this meta-analysis and the use of heterogeneous research methodologies in these studies may limit the accuracy of these findings. Nevertheless, these findings have important implications for the global plan to eliminate HIV infections in children. First, they suggest that women living in regions where HIV infection is common should be offered repeat HIV testing (using sensitive methods to enhance early detection of infection) during pregnancy and in the postpartum period to detect incident HIV infections, and should be promptly referred to HIV care and treatment. Second, they suggest that prevention of HIV transmission during pregnancy and postpartum should be prioritized, for example, by counseling women about the need to use condoms to prevent transmission during this period of their lives.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001608.
Information is available from the US National Institute of Allergy and Infectious Diseases on HIV infection and AIDS
NAM/aidsmap provides basic information about HIV/AIDS and summaries of recent research findings on HIV care and treatment
Information is available from Avert, an international AIDS charity, on many aspects of HIV/AIDS, including information on children and HIV/AIDS and on the prevention of mother-to-child transmission of HIV (in English and Spanish)
The 2013 UNAIDS World AIDS Day Report provides information about the AIDS epidemic and efforts to halt it; the 2013 UNAIDS Progress Report on the Global Plan provides information on progress towards eliminating new HIV infections among children; the UNAIDS Believe it. Do it website provides information about the campaign to support the UNAIDS global plan
Personal stories about living with HIV/AIDS, including stories from young people infected with HIV, are available through Avert, NAM/aidsmap, and Healthtalkonline
doi:10.1371/journal.pmed.1001608
PMCID: PMC3934828  PMID: 24586123
11.  When Do HIV-Infected Women Disclose Their HIV Status to Their Male Partner and Why? A Study in a PMTCT Programme, Abidjan 
PLoS Medicine  2007;4(12):e342.
Background
In Africa, women tested for HIV during antenatal care are counselled to share with their partner their HIV test result and to encourage partners to undertake HIV testing. We investigate, among women tested for HIV within a prevention of mother-to-child transmission of HIV (PMTCT) programme, the key moments for disclosure of their own HIV status to their partner and the impact on partner HIV testing.
Methods and Findings
Within the Ditrame Plus PMTCT project in Abidjan, 546 HIV-positive and 393 HIV-negative women were tested during pregnancy and followed-up for two years after delivery. Circumstances, frequency, and determinants of disclosure to the male partner were estimated according to HIV status. The determinants of partner HIV testing were identified according to women's HIV status. During the two-year follow-up, disclosure to the partner was reported by 96.7% of the HIV-negative women, compared to 46.2% of HIV-positive women (χ2 = 265.2, degrees of freedom [df] = 1, p < 0.001). Among HIV-infected women, privileged circumstances for disclosure were just before delivery, during early weaning (at 4 mo to prevent HIV postnatal transmission), or upon resumption of sexual activity. Formula feeding by HIV-infected women increased the probability of disclosure (adjusted odds ratio 1.54, 95% confidence interval 1.04–2.27, Wald test = 4.649, df = 1, p = 0.031), whereas household factors such as having a co-spouse or living with family reduced the probability of disclosure. The proportion of male partners tested for HIV was 23.1% among HIV-positive women and 14.8% among HIV-negative women (χ2 = 10.04, df = 1, p = 0.002). Partners of HIV-positive women who were informed of their wife's HIV status were more likely to undertake HIV testing than those not informed (37.7% versus 10.5%, χ2 = 56.36, df = 1, p < 0.001).
Conclusions
In PMTCT programmes, specific psychosocial counselling and support should be provided to women during the key moments of disclosure of HIV status to their partners (end of pregnancy, weaning, and resumption of sexual activity). This support could contribute to improving women's adherence to the advice given to prevent postnatal and sexual HIV transmission.
In a mother-to-child HIV prevention program in Côte d'Ivoire, Annabel Desgrées-du-Loû and colleagues identify three junctures at which women tend to disclose their HIV status to partners.
Editors' Summary
Background.
Since the first reported case of AIDS (acquired immunodeficiency syndrome) in 1981, the number of people infected with the human immunodeficiency virus (HIV), which causes AIDS, has risen steadily. By the end of 2006, nearly 40 million people were infected, 25 million of them in sub-Saharan Africa. HIV is most often spread by having unprotected sex with an infected partner. In Africa, most sexual transmission of HIV is between partners in stable relationships—many such couples do not adopt measures that prevent viral transmission, such as knowing the HIV status of both partners and using condoms if one partner is HIV-positive. HIV can also pass from a mother to her baby during pregnancy, labor, or delivery, or through breastfeeding. Mother-to-child transmission (MTCT) of HIV can be reduced by giving anti-HIV drugs to the mother during pregnancy and labor and to her newborn baby, and by avoiding breastfeeding or weaning the baby early.
Why Was This Study Done?
Many African countries have programs for prevention of MTCT (PMTCT) that offer pregnant women prenatal HIV counseling and testing. As a result, women are often the first member of a stable relationship to know their HIV status. PMTCT programs advise women to disclose their HIV test result to their partner and to encourage him to have an HIV test. But for many women, particularly those who are HIV-positive, talking to their partner about HIV/AIDS is hard because of fears of rejection (which could mean loss of housing and food) or accusations of infidelity. Knowing more about when women disclose their HIV status and what makes them decide to do so would help the people running PMTCT programs to support women during the difficult process of disclosure. In this study, the researchers have investigated when and why women participating in a PMTCT research project in Abidjan (Côte d'Ivoire) told their partner about their HIV status and the impact this disclosure had on their partner's uptake of HIV testing.
What Did the Researchers Do and Find?
At regular follow-up visits, the researchers asked women in the Abidjan PMTCT project whether they had told their partners their HIV status and whether they were breast-feeding or had resumed sexual activity. Nearly all the women who tested negative for HIV, but slightly fewer than half of the HIV-positive (infected) women had told their partner about their HIV status by two years after childbirth. Two-thirds of the HIV-positive women who disclosed their status did so before delivery. Other key times for disclosure were at early weaning (4 months after birth) for women who breast-fed their babies, and when sexual activity resumed. HIV-positive women who bottle fed their babies from birth were more likely to tell their partners of their status than women who breast-fed. Factors that prevented women disclosing their HIV status included living in a polygamous relationship or living separately from their partners. Finally, the researchers report that the partners of HIV-positive women who disclosed their HIV status were about three times more likely to take an HIV test than the partners of HIV-positive women who did not disclose.
What Do These Findings Mean?
These findings identify three key times when women who have had an HIV test during pregnancy are likely to disclose their HIV status to their partner. The main one is before delivery and relates, in part, to how the mother plans to feed her baby. To bottle feed in Abidjan, women need considerable support from their partners and this may be the impetus for disclosing their HIV status. Disclosure at early weaning may reflect the woman's need to enlist her partner's support for this unusual decision—the normal time for weaning in Abidjan is 17 months. Finally, disclosure when sexual activity resumes may be necessary so that the woman can explain why she wants to use condoms. Although these findings need confirmation in other settings, targeting counseling and support within PMTCT programs to these key moments might help HIV-positive women to tell their partners about their status. This, hopefully, would help to reduce sexual transmission of HIV within stable relationships in sub-Saharan Africa.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0040342.
Information is available from the US National Institute of Allergy and Infectious Diseases on HIV infection and AIDS and on HIV infection in women
HIV InSite has comprehensive information on all aspects of HIV/AIDS
Women Children and HIV provides extensive information on prevention of mother-to-child transmission of HIV in developing countries
Information is available from Avert, an international AIDS charity, on HIV and AIDS in Africa and on HIV and AIDS prevention
AIDSinfo, a service of the US Department of Health and Human Services provideshealth information for HIV-positive pregnant women (in English and Spanish)
doi:10.1371/journal.pmed.0040342
PMCID: PMC2100145  PMID: 18052603
12.  Is Food Insecurity Associated with HIV Risk? Cross-Sectional Evidence from Sexually Active Women in Brazil 
PLoS Medicine  2012;9(4):e1001203.
Alexander Tsai and colleagues show that in sexually active women in Brazil severe food insecurity with hunger was positively associated with symptoms potentially indicative of sexually transmitted infection and with reduced odds of condom use.
Background
Understanding how food insecurity among women gives rise to differential patterning in HIV risks is critical for policy and programming in resource-limited settings. This is particularly the case in Brazil, which has undergone successive changes in the gender and socio-geographic composition of its complex epidemic over the past three decades. We used data from a national survey of Brazilian women to estimate the relationship between food insecurity and HIV risk.
Methods and Findings
We used data on 12,684 sexually active women from a national survey conducted in Brazil in 2006–2007. Self-reported outcomes were (a) consistent condom use, defined as using a condom at each occasion of sexual intercourse in the previous 12 mo; (b) recent condom use, less stringently defined as using a condom with the most recent sexual partner; and (c) itchy vaginal discharge in the previous 30 d, possibly indicating presence of a sexually transmitted infection. The primary explanatory variable of interest was food insecurity, measured using the culturally adapted and validated Escala Brasiliera de Segurança Alimentar. In multivariable logistic regression models, severe food insecurity with hunger was associated with a reduced odds of consistent condom use in the past 12 mo (adjusted odds ratio [AOR] = 0.67; 95% CI, 0.48–0.92) and condom use at last sexual intercourse (AOR = 0.75; 95% CI, 0.57–0.98). Self-reported itchy vaginal discharge was associated with all categories of food insecurity (with AORs ranging from 1.46 to 1.94). In absolute terms, the effect sizes were large in magnitude across all outcomes. Underweight and/or lack of control in sexual relations did not appear to mediate the observed associations.
Conclusions
Severe food insecurity with hunger was associated with reduced odds of condom use and increased odds of itchy vaginal discharge, which is potentially indicative of sexually transmitted infection, among sexually active women in Brazil. Interventions targeting food insecurity may have beneficial implications for HIV prevention in resource-limited settings.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
At the beginning of the AIDS epidemic, more men than women were infected with HIV, the virus that causes AIDS, but currently half of all HIV-positive adults are women. Most women become infected with HIV through unprotected sexual intercourse with an infected male partner. Biologically, women are twice as likely to become infected through unprotected heterosexual intercourse as men. Moreover, women are often unable to negotiate condom use because of unequal gender relations—men can insist on unprotected sexual intercourse in many relationships. Another factor often related to unequal gender relations that may shape women's risk of exposure to HIV is food insecurity—limited or uncertain access to enough nutritionally adequate and safe food for an active, healthy life. Recent studies done in sub-Saharan Africa suggest that food insecurity can affect women's engagement in risky sexual behaviors such as unprotected sex, transactional sex (sexual relationships that involve the giving of goods or services such as free lodgings), and commercial sex work.
Why Was This Study Done?
Policymakers planning HIV prevention strategies in resource-limited settings need to know whether food insecurity affects sexual risk taking among women. If it increases risk taking, then interventions that target food insecurity should improve the effectiveness of HIV prevention strategies. However, little is known about food insecurity and sexual risk taking outside sub-Saharan Africa. In this cross-sectional study (a study that characterizes a population at a single point in time), the researchers investigate whether food insecurity is associated with risky sexual behavior among sexually active women in Brazil, a country where the number of new heterosexually transmitted HIV infections among women is increasing. Condom promotion is the mainstay of Brazil's HIV prevention strategy, but less than half of the population reports the use of a condom whenever sexual intercourse occurs (consistent condom use) or at last sexual intercourse (recent condom use), and a greater proportion of men than women report condom use, possibly because of unequal power relations between men and women.
What Did the Researchers Do and Find?
The researchers obtained data on consistent condom use, recent condom use, and self-reported itchy vaginal discharge in the previous 30 days (used here as an indication that a woman may have a sexually transmitted infection) for 12,684 sexually active women from a national survey conducted in Brazil in 2006–2007. They then used multivariable logistic regression (a statistical method) to investigate the association between these outcomes and food insecurity, which was measured using the Escala Brasiliera de Insegurança Alimentar, an 18-item questionnaire that asks people to recall information about the quantity and quality of food available to them over the previous three months. Severe food insecurity with hunger (the most extreme category of food insecurity) was associated with an adjusted odds ratio (AOR) for consistent condom use of 0.67. That is, women who reported severe food insecurity were two-thirds as likely to use a condom whenever they had sexual intercourse as women who were food secure, after adjustment for other factors that might have affected condom use. The probability of consistent condom use was 15% among women who were food secure but only 10.5% among women who had the worst food security. Severe food insecurity with hunger was also associated with a reduced odds of recent condom use (AOR = 0.75), whereas all categories of food insecurity increased the odds of a recent itchy vaginal discharge.
What Do These Findings Mean?
These findings indicate that severe food insecurity with hunger is associated with reduced condom use and with increased occurrence of symptoms that may indicate sexually transmitted disease among sexually active women in Brazil. Because the study looked at women at only a single time point, these findings do not show that food insecurity causes risky sexual behavior. Moreover, these findings may not be generalizable to other settings, and they do not distinguish between regular condom use with a regular partner and regular condom use with casual partners. Also, although the researchers investigated two hypothesized explanations—lack of control in sexual relations and chronic energy deficiency—neither of these factors could explain why food insecurity is associated with risky sexual behavior. Nevertheless, these findings suggest that interventions that target sexual risk reduction behaviors are unlikely to be optimally effective if food insecurity is not taken into account, and, thus, the researchers conclude, HIV prevention strategies in Brazil should include interventions that target food insecurity.
Additional Information
Please access these web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001203.
Information is available from the US National Institute of Allergy and Infectious Diseases on all aspects of HIV infection and AIDS
NAM/aidsmap provides basic information about HIV/AIDS, and summaries of recent research findings on HIV care and treatment (in several languages)
Information is available from Avert, an international AIDS charity on many aspects of HIV/AIDS, including detailed information on HIV and AIDS prevention, women, HIV, and AIDS, and HIV and AIDS in Brazil (in English and Spanish); personal stories of women living with HIV are available
HIV InSite provides comprehensive and up-to-date information on all aspects of HIV/AIDS from the University of California at San Francisco
Additional patient stories about living with HIV/AIDS are available through the charity website Healthtalkonline
A primer on food security from the Food and Agriculture Organization of the United Nations is available
Information about the 2006–2007 Brazilian national survey on health in women and children is available in Portuguese; a profile of food security in Brazil is also available (some information in English but mainly in Portuguese)
doi:10.1371/journal.pmed.1001203
PMCID: PMC3323512  PMID: 22505852
13.  Routine HIV Testing in Botswana: A Population-Based Study on Attitudes, Practices, and Human Rights Concerns 
PLoS Medicine  2006;3(7):e261.
Background
The Botswana government recently implemented a policy of routine or “opt-out” HIV testing in response to the high prevalence of HIV infection, estimated at 37% of adults.
Methods and Findings
We conducted a cross-sectional, population-based study of 1,268 adults from five districts in Botswana to assess knowledge of and attitudes toward routine testing, correlates of HIV testing, and barriers and facilitators to testing, 11 months after the introduction of this policy. Most participants (81%) reported being extremely or very much in favor of routine testing. The majority believed that this policy would decrease barriers to testing (89%), HIV-related stigma (60%), and violence toward women (55%), and would increase access to antiretroviral treatment (93%). At the same time, 43% of participants believed that routine testing would lead people to avoid going to the doctor for fear of testing, and 14% believed that this policy could increase gender-based violence related to testing. The prevalence of self-reported HIV testing was 48%. Adjusted correlates of testing included female gender (AOR = 1.5, 95% CI = 1.1–1.9), higher education (AOR = 2.0, 95% CI = 1.5–2.7), more frequent healthcare visits (AOR = 1.9, 95% CI = 1.3–2.7), perceived access to HIV testing (AOR = 1.6, 95% CI = 1.1–2.5), and inconsistent condom use (AOR = 1.6, 95% CI = 1.2–2.1). Individuals with stigmatizing attitudes toward people living with HIV and AIDS were less likely to have been tested for HIV/AIDS (AOR = 0.7, 95% CI = 0.5–0.9) or to have heard of routine testing (AOR = 0.59, 95% CI = 0.45–0.76). While experiences with voluntary and routine testing overall were positive, 68% felt that they could not refuse the HIV test. Key barriers to testing included fear of learning one's status (49%), lack of perceived HIV risk (43%), and fear of having to change sexual practices with a positive HIV test (33%).
Conclusions
Routine testing appears to be widely supported and may reduce barriers to testing in Botswana. As routine testing is adopted elsewhere, measures should be implemented to assure true informed consent and human rights safeguards, including protection from HIV-related discrimination and protection of women against partner violence related to testing.
Editors' Summary
Background.
In 2005, there were 5 million new infections with the human immunodeficiency virus (HIV), and the disease it causes—acquired immunodeficiency syndrome (AIDS)—killed three million people. Despite the increased availability of drugs that can fight HIV (antiretrovirals), the AIDS epidemic continues to grow, particularly in sub-Saharan Africa. To halt it, more needs to be done to prevent the spread of HIV. Education about safe sex can help—HIV is most commonly spread through unprotected sex with an infected partner—but increasing HIV testing is of paramount importance. Unfortunately, the uptake of voluntary counseling and testing in sub-Saharan Africa is worryingly low. Fear of being stigmatized—socially disgraced—and discriminated against, fears about the positive result itself, and worries about access to antiretroviral drugs are all putting people off being tested.
Why Was This Study Done?
In Botswana, one in three adults is infected with HIV. Since 2002, antiretroviral drugs have been freely available but enrollment in the Botswana National Treatment Program during its first two years was slow, in part due to inadequate uptake of voluntary HIV testing. Consequently, in early 2004, the government introduced a policy of routine HIV testing in which all patients are tested for HIV when they visit their doctor unless they opt out. A major aim of this approach to HIV testing, which was formally recommended in June 2004 by UNAIDS and the World Health Organization, is to increase uptake of HIV testing and treatment, and to reduce HIV-related stigma by treating the HIV test like any other routine medical procedure. However, there are fears that the policy could back-fire—people might not visit their doctors, for example, because they are afraid of being tested and think that they will not be able to refuse the test. In this study, the researchers investigated knowledge of and attitudes to routine testing in Botswana to understand better the consequences of a routine testing policy.
What Did the Researchers Do and Find?
The researchers interviewed adults throughout Botswana about their knowledge of and attitudes to routine HIV testing 11 months after introduction of the policy. Only half of the participants had heard of routine testing before being interviewed but nearly all were in favor of routine testing. More than half thought it would reduce HIV-related stigma and the violence toward women that is associated with an HIV-positive status. However, almost half believed that routine testing might prevent people from going to the doctor because of fear of testing and a few thought the policy would increase violence against women. Nearly half of the interviewees had had an HIV test and the researchers found, for example, that women were more likely to have been tested than men and that people with stigmatizing attitudes toward people living with HIV and AIDS were less likely to be tested. Fear of learning one's HIV status, lack of perceived risk, and fear of having to change sexual practices if positive all stopped people taking the test. Finally, although experiences with testing were generally positive, approximately two-thirds of interviewees who had been tested felt that it would have been difficult to refuse the test.
What Do These Findings Mean?
These results show that there is widespread support for routine HIV testing in Botswana, a finding supported by recent increases in treatment uptake. Routine testing, write the researchers, holds significant promise for the prevention and treatment of HIV/AIDS in Botswana and elsewhere. In particular, increasing the number of people tested for HIV may reduce HIV-related stigma, which should further increase testing and hopefully slow the spread of HIV. But the results of this study also highlight some areas of concern. Whenever HIV testing policies are implemented, human rights must be protected by ensuring that patients have all the information necessary to make an informed and free decision about being tested, by providing protection for women against violence related to HIV status, and by ensuring total confidentiality. Careful monitoring of Botswana's program and similar programs will be needed to ensure that these human rights are fully met, conclude the researchers.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0030261
• US National Institute of Allergy and Infectious Diseases factsheet on HIV infection and AIDS
• US Department of Health and Human Services information on AIDS
• US Centers for Disease Control and Prevention information on HIV/AIDS
• UNAIDS and World Health Organization 2004 policy statement on HIV testing
• AVERT, a UK-based charity, provides information about HIV and AIDS in Botswana
A cross-sectional, population-based study of 1,268 adults from five districts in Botswana showed that routine HIV testing appears to be widely supported and may reduce barriers to HIV testing.
doi:10.1371/journal.pmed.0030261
PMCID: PMC1502152  PMID: 16834458
14.  Association between Prenatal Exposure to Antiretroviral Therapy and Birth Defects: An Analysis of the French Perinatal Cohort Study (ANRS CO1/CO11) 
PLoS Medicine  2014;11(4):e1001635.
Jeanne Sibiude and colleagues use the French Perinatal Cohort to estimate the prevalence of birth defects in children born to HIV-infected women receiving antiretroviral therapy during pregnancy.
Please see later in the article for the Editors' Summary
Background
Antiretroviral therapy (ART) has major benefits during pregnancy, both for maternal health and to prevent mother-to-child transmission of HIV. Safety issues, including teratogenic risk, need to be evaluated. We estimated the prevalence of birth defects in children born to HIV-infected women receiving ART during pregnancy, and assessed the independent association of birth defects with each antiretroviral (ARV) drug used.
Methods and Findings
The French Perinatal Cohort prospectively enrolls HIV-infected women delivering in 90 centers throughout France. Children are followed by pediatricians until 2 y of age according to national guidelines.
We included 13,124 live births between 1994 and 2010, among which, 42% (n = 5,388) were exposed to ART in the first trimester of pregnancy. Birth defects were studied using both European Surveillance of Congenital Anomalies (EUROCAT) and Metropolitan Atlanta Congenital Defects Program (MACDP) classifications; associations with ART were evaluated using univariate and multivariate logistic regressions. Correction for multiple comparisons was not performed because the analyses were based on hypotheses emanating from previous findings in the literature and the robustness of the findings of the current study. The prevalence of birth defects was 4.4% (95% CI 4.0%–4.7%), according to the EUROCAT classification. In multivariate analysis adjusting for other ARV drugs, maternal age, geographical origin, intravenous drug use, and type of maternity center, a significant association was found between exposure to zidovudine in the first trimester and congenital heart defects: 2.3% (74/3,267), adjusted odds ratio (AOR) = 2.2 (95% CI 1.3–3.7), p = 0.003, absolute risk difference attributed to zidovudine +1.2% (95% CI +0.5; +1.9%). Didanosine and indinavir were associated with head and neck defects, respectively: 0.5%, AOR = 3.4 (95% CI 1.1–10.4), p = 0.04; 0.9%, AOR = 3.8 (95% CI 1.1–13.8), p = 0.04. We found a significant association between efavirenz and neurological defects (n = 4) using the MACDP classification: AOR = 3.0 (95% CI 1.1–8.5), p = 0.04, absolute risk +0.7% (95% CI +0.07%; +1.3%). But the association was not significant using the less inclusive EUROCAT classification: AOR = 2.1 (95% CI 0.7–5.9), p = 0.16. No association was found between birth defects and lopinavir or ritonavir with a power >85% for an odds ratio of 1.5, nor for nevirapine, tenofovir, stavudine, or abacavir with a power >70%. Limitations of the present study were the absence of data on termination of pregnancy, stillbirths, tobacco and alcohol intake, and concomitant medication.
Conclusions
We found a specific association between in utero exposure to zidovudine and heart defects; the mechanisms need to be elucidated. The association between efavirenz and neurological defects must be interpreted with caution. For the other drugs not associated with birth defects, the results were reassuring. Finally, whatever the impact that some ARV drugs may have on birth defects, it is surpassed by the major role of ART in the successful prevention of mother-to-child transmission of HIV.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
AIDS and HIV infection are commonly treated with antiretroviral therapy (ART), a combination of individual drugs that work together to prevent the replication of the virus and further spread of the infection. Starting in the 1990s, studies have shown that ART of HIV-infected women can substantially reduce transmission of the virus to the child during pregnancy and birth. Based on these results, ART was subsequently recommended for pregnant women. Since 2004, ART has been standard therapy for pregnant women with HIV/AIDS in high-income countries, and it is now recommended for all HIV-infected women worldwide. Several different antiviral drug combinations have been shown to be effective and are used to prevent mother-to-infant transmission. However, as with any other drugs taken during pregnancy, there is concern that ART can harm the developing fetus.
Why Was This Study Done?
Several previous studies have assessed the risk that ART taken by a pregnant woman might pose to her developing fetus, but the results have been inconsistent. Animal studies suggested an elevated risk for some drugs but not others. While some clinical studies have reported increases in birth defects in children born to mothers on ART, others have shown no such increase.
The discrepancy may be due to differences between the populations included in the studies and the different methods used to diagnose birth defects. Additional large studies are therefore necessary to obtain more and better evidence on the potential harm of individual anti-HIV drugs to children exposed during pregnancy. So in this study, the authors conducted a large cohort study in France to assess the relationship between different antiretroviral drugs and specific birth defects.
What Did the Researchers Do and Find?
The researchers used a large national health database known as the French Perinatal Cohort that contains information on HIV-infected mothers who delivered infants in 90 centers throughout France. Pediatricians follow all children, whatever their HIV status, to two years of age, and health statistics are collected according to national health-care guidelines. Analyzing the records, the researchers estimated the rate at which birth defects occurred in children exposed to antiretroviral drugs during pregnancy.
The researchers included 13,124 children who were born alive between 1994 and 2010 and had been exposed to ART during pregnancy. Children exposed in the first trimester of pregnancy, and those exposed during the second or third trimester, were compared to a control group (children not exposed to the drug during the whole pregnancy). Using two birth defect classification systems (EUROCAT and MACDP—MACDP collects more details on disease classification than EUROCAT), the researchers sought to detect a link between the occurrence of birth defects and exposure to individual antiretroviral drugs.
They found a small increase in the risk for heart defects in children with exposure to zidovudine. They also found an association between efavirenz exposure and a small increase in neurological defects, but only when using the MACDP classification system. The authors found no association between other antiretroviral drugs, including nevirapine (acting similar to efavirenz); tenofovir, stavudine, and abacavir (all three acting similar to zidovudine); and lopinavir and ritonavir (proteinase inhibitors) and any type of birth defect.
What Do These Findings Mean?
These findings show that, overall, the risks of birth defects in children exposed to antiretroviral drugs in utero are small when considering the clear benefit of preventing mother-to-child transmission of HIV. However, where there are safe and effective alternatives, it might be appropriate to avoid use by pregnant women of those drugs that are associated with elevated risks of birth defects.
Worldwide, a large number of children are exposed to zidovudine in utero, and these results suggest (though cannot prove) that these children may be at a slightly higher risk of heart defects. Current World Health Organization (WHO) guidelines for the prevention of mother-to-child transmission no longer recommend zidovudine for first-line therapy.
The implications of the higher rate of neurological birth defects observed in infants exposed to efavirenz in the first trimester are less clear. The EUROCAT classification excludes minor neurological abnormalities without serious medical consequences, and so the WHO guidelines that stress the importance of careful clinical follow-up of children with exposure to efavirenz seem adequate, based on the findings of this study. The study is limited by the lack of data on the use of additional medication and alcohol and tobacco use, which could have a direct impact on fetal development, and by the absence of data on birth defects and antiretroviral drug exposure from low-income countries. However, the findings of this study overall are reassuring and suggest that apart from zidovudine and possibly efavirenz, other antiretroviral drugs are not associated with birth defects, and their use during pregnancy does not pose a risk to the infant.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001635.
This study is further discussed in a PLOS Medicine Perspective by Mofenson and Watts
The World Health Organization has a webpage on mother-to-child transmission of HIV
The US National Institutes of Health provides links to additional information on mother-to-child transmission of HIV
The Elizabeth Glaser Pediatric AIDS Foundation also has a webpage on mother-to-child transmission
The French Perinatal Cohort has a webpage describing the cohort and its main publications (in French, with a summary in English)
doi:10.1371/journal.pmed.1001635
PMCID: PMC4004551  PMID: 24781315
15.  No Treatment versus 24 or 60 Weeks of Antiretroviral Treatment during Primary HIV Infection: The Randomized Primo-SHM Trial 
PLoS Medicine  2012;9(3):e1001196.
In a three-arm randomized trial conducted among adult patients in HIV treatment centers in The Netherlands, Marlous Grijsen and colleagues examine the effects of temporary combination antiretroviral therapy during primary HIV infection.
Background
The objective of this study was to assess the benefit of temporary combination antiretroviral therapy (cART) during primary HIV infection (PHI).
Methods and Findings
Adult patients with laboratory evidence of PHI were recruited in 13 HIV treatment centers in the Netherlands and randomly assigned to receive no treatment or 24 or 60 wk of cART (allocation in a 1∶1∶1 ratio); if therapy was clinically indicated, participants were randomized over the two treatment arms (allocation in a 1∶1 ratio). Primary end points were (1) viral set point, defined as the plasma viral load 36 wk after randomization in the no treatment arm and 36 wk after treatment interruption in the treatment arms, and (2) the total time that patients were off therapy, defined as the time between randomization and start of cART in the no treatment arm, and the time between treatment interruption and restart of cART in the treatment arms. cART was (re)started in case of confirmed CD4 cell count <350 cells/mm3 or symptomatic HIV disease. In total, 173 participants were randomized. The modified intention-to-treat analysis comprised 168 patients: 115 were randomized over the three study arms, and 53 randomized over the two treatment arms. Of the 115 patients randomized over the three study arms, mean viral set point was 4.8 (standard deviation 0.6) log10 copies/ml in the no treatment arm, and 4.0 (1.0) and 4.3 (0.9) log10 copies/ml in the 24- and 60-wk treatment arms (between groups: p<0.001). The median total time off therapy in the no treatment arm was 0.7 (95% CI 0.0–1.8) y compared to 3.0 (1.9–4.2) and 1.8 (0.5–3.0) y in the 24- and 60-wk treatment arms (log rank test, p<0.001). In the adjusted Cox analysis, both 24 wk (hazard ratio 0.42 [95% CI 0.25–0.73]) and 60 wk of early treatment (hazard ratio 0.55 [0.32–0.95]) were associated with time to (re)start of cART.
Conclusions
In this trial, temporary cART during PHI was found to transiently lower the viral set point and defer the restart of cART during chronic HIV infection.
Trial registration
Current Controlled Trials ISRCTN59497461
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Every year, nearly three million people become infected with HIV, the virus that causes AIDS. The first stage of HIV infection—primary HIV infection—lasts a few weeks and often goes undetected, although most individuals develop a short, flu-like illness. During this stage of infection, the immune system begins to make antibodies to HIV. The second stage of HIV infection, which lasts many years, also has no major symptoms but, during this stage, HIV slowly destroys immune system cells, including CD4 cells, a type of lymphocyte. Eventually, the immune system is unable to fight off other infections and patients enter the third phase of HIV infection—symptomatic HIV infection. The final stage—AIDS—is characterized by the occurrence of one or more AIDS-defining conditions, which include severe but unusual infections and several types of cancer. Early in the AIDS epidemic, most HIV-positive people died within ten years of infection. Nowadays, although there is still no cure for HIV infection, HIV has become a chronic disease because of the availability of combination antiretroviral therapy (cART; cocktails of several powerful drugs). This means that many HIV-positive people have a near-normal life span.
Why Was This Study Done?
It is currently recommended that people start cART when their CD4 count falls below 350 CD4 cells per cubic milliliter (cells/mm3) of blood, when they develop severe constitutional symptoms such as fever lasting longer than a month, or when they develop an AIDS-defining condition. But could a short course of cART during primary HIV infection be clinically beneficial? Some, but not all, nonrandomized studies have shown that such treatment reduces the viral set point (the stabilized viral load that is reached after the immune system begins to make antibodies to HIV; the viral load is the amount of virus in the blood) and slows the decline of CD4 cell count in patients. In this randomized trial (the Primo-SHM trial), the researchers assess the clinical benefit of temporary cART initiated during primary HIV infection by measuring its effects on the viral set point and on when patients have to restart cART during chronic HIV infection. In a randomized controlled trial, patients are assigned by the play of chance to receive different treatments and then followed to compare the effects of these treatments.
What Did the Researchers Do and Find?
The researchers assigned 168 patients with primary HIV infection to receive no treatment, 24 weeks of cART, or 60 weeks of cART. They measured the viral set point (the viral load in the blood 36 weeks after randomization in the no treatment arm and 36 weeks after cART interruption in the treatment arms) and determined the time off therapy (the time between randomization and the start of cART in the no treatment arm, and the time between treatment interruption and restart of cART in the treatment arms) for each patient. cART was (re)started following two consecutive CD4 counts below 350 cells/mm3 or when symptomatic HIV disease developed. The average viral set point was lower in the patients who received early cART than in those who had no treatment. Moreover, on average, the patients in the no treatment arm started cART 0.7 years after randomization whereas those in the 24- and 60-week treatment arms restarted cART after 3.0 and 1.8 years, respectively. There was no statistically significant difference between the 24-week and 60-week treatment arms in time off therapy.
What Do These Findings Mean?
These findings suggest that temporary cART during primary HIV infection can transiently lower the viral set point and can delay the need to restart cART during chromic HIV infection. They also suggest that 24 weeks of cART during primary HIV is as effective as 60 weeks of treatment. These findings need to be confirmed in other settings, and follow-up studies are needed to evaluate the long-term benefits of early temporary cART, but given the short time between cART interruption and treatment restart, the researchers suggest that not interrupting early cART, but instead continuing it for life, should be considered. However, they add, because patients are often physically and emotionally distressed at this stage of HIV infection, adherence to cART during primary HIV infection may be suboptimal, and so patients with primary HIV infection should be advised to start cART only when they feel ready to start treatment.
Additional Information
Please access these web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001196.
Information is available from the US National Institute of Allergy and infectious diseases on HIV infection and AIDS, including information on the clinical progression of HIV infection
NAM/aidsmap provides information about HIV/AIDS, including a factsheet on primary infection
Information is available from Avert, an international AIDS charity on many aspects of HIV/AIDS, including detailed information on HIV treatment and care and on the stages of HIV infection (in English and Spanish)
The World Health Organization's 2010 antiretroviral therapy guidelines provide recommendations on when to initiate cART
Information about Primo-SHM is available
Patient stories about living with HIV/AIDS are available through Avert and through the charity website Healthtalkonline
doi:10.1371/journal.pmed.1001196
PMCID: PMC3313945  PMID: 22479156
16.  The Role of HIV-Related Stigma in Utilization of Skilled Childbirth Services in Rural Kenya: A Prospective Mixed-Methods Study 
PLoS Medicine  2012;9(8):e1001295.
Janet Turan and colleagues examined the role of the perception of women in rural Kenya of HIV-related stigma during pregnancy on their subsequent utilization of maternity services.
Background
Childbirth with a skilled attendant is crucial for preventing maternal mortality and is an important opportunity for prevention of mother-to-child transmission of HIV. The Maternity in Migori and AIDS Stigma Study (MAMAS Study) is a prospective mixed-methods investigation conducted in a high HIV prevalence area in rural Kenya, in which we examined the role of women's perceptions of HIV-related stigma during pregnancy in their subsequent utilization of maternity services.
Methods and Findings
From 2007–2009, 1,777 pregnant women with unknown HIV status completed an interviewer-administered questionnaire assessing their perceptions of HIV-related stigma before being offered HIV testing during their first antenatal care visit. After the visit, a sub-sample of women was selected for follow-up (all women who tested HIV-positive or were not tested for HIV, and a random sample of HIV-negative women, n = 598); 411 (69%) were located and completed another questionnaire postpartum. Additional qualitative in-depth interviews with community health workers, childbearing women, and family members (n = 48) aided our interpretation of the quantitative findings and highlighted ways in which HIV-related stigma may influence birth decisions. Qualitative data revealed that health facility birth is commonly viewed as most appropriate for women with pregnancy complications, such as HIV. Thus, women delivering at health facilities face the risk of being labeled as HIV-positive in the community. Our quantitative data revealed that women with higher perceptions of HIV-related stigma (specifically those who held negative attitudes about persons living with HIV) at baseline were subsequently less likely to deliver in a health facility with a skilled attendant, even after adjusting for other known predictors of health facility delivery (adjusted odds ratio = 0.44, 95% CI 0.22–0.88).
Conclusions
Our findings point to the urgent need for interventions to reduce HIV-related stigma, not only for improving quality of life among persons living with HIV, but also for better health outcomes among all childbearing women and their families.
Please see later in the article for the Editors' Summary.
Editors' Summary
Background
Every year, nearly 350,000 women die from pregnancy- or childbirth-related complications. Almost all these “maternal” deaths occur in developing countries. In sub-Saharan Africa, for example, the maternal mortality ratio (the number of maternal deaths per 100,000 live births) is 500 whereas in industrialized countries it is only 12. Most maternal deaths are caused by hemorrhage (severe bleeding after childbirth), post-delivery infections, obstructed (difficult) labor, and blood pressure disorders during pregnancy. All these conditions can be prevented if women have access to adequate reproductive health services and if trained health care workers are present during delivery. Notably, in sub-Saharan Africa, infection with HIV (the virus that causes AIDS) is an increasingly important contributor to maternal mortality. HIV infection causes maternal mortality directly by increasing the occurrence of pregnancy complications and indirectly by increasing the susceptibility of pregnant women to malaria, tuberculosis, and other “opportunistic” infections—HIV-positive individuals are highly susceptible to other infections because HIV destroys the immune system.
Why Was This Study Done?
Although skilled delivery attendants reduce maternal mortality, there are many barriers to their use in developing countries including cost and the need to travel long distances to health facilities. Fears and experiences of HIV-related stigma and discrimination (prejudice, negative attitudes, abuse, and maltreatment directed at people living with HIV) may also be a barrier to the use of skilled childbirth service. Maternity services are prime locations for HIV testing and for the provision of interventions for the prevention of mother-to-child transmission (PMTCT) of HIV, so pregnant women know that they will have to “deal with” the issue of HIV when visiting these services. In this prospective mixed-methods study, the researchers examine the role of pregnant women's perceptions of HIV-related stigma in their subsequent use of maternity services in Nyanza Province, Kenya, a region where 16% women aged 15–49 are HIV-positive and where only 44.2% of mothers give birth in a health facility. A mixed-methods study combines qualitative data—how people feel about an issue—with quantitative data—numerical data about outcomes.
What Did the Researchers Do and Find?
In the Maternity in Migori and AIDS Stigma (MAMAS) study, pregnant women with unknown HIV status living in rural regions of Nyanza Province answered questions about their perceptions of HIV-related stigma before being offered HIV testing during their first antenatal clinic visit. After delivery, the researchers asked the women who tested HIV positive or were not tested for HIV and a sample of HIV-negative women where they had delivered their baby. They also gathered qualitative information about barriers to maternity and HIV service use by interviewing childbearing women, family members, and community health workers. The qualitative data indicate that labor in a health facility is commonly viewed as being most appropriate for women with pregnancy complications such as HIV infection. Thus, women delivering at health facilities risk being labeled as HIV positive, a label that the community associates with promiscuity. The quantitative data indicate that women with more negative attitudes about HIV-positive people (higher perceptions of HIV-related stigma) at baseline were about half as likely to deliver in a health facility with a skilled attendant as women with more positive attitudes about people living with HIV.
What Do These Findings Mean?
These findings suggest that HIV-related stigma is associated with the low rate of delivery by skilled attendants in rural areas of Nyanza Province and possibly in other rural regions of sub-Saharan Africa. Community mobilization efforts aimed at increasing the use of PMTCT services may be partly responsible for the strong perception that delivery in a health facility is most appropriate for women with HIV and other pregnancy complications and may have inadvertently strengthened the perception that women who give birth in such facilities are likely to be HIV positive. The researchers suggest, therefore, that health messages should stress that delivery in a health facility is recommended for all women, not just HIV-positive women or those with pregnancy complications, and that interventions should be introduced to reduce HIV-related stigma. This combined strategy has the potential to increase the use of maternity services by all women and the use of HIV and PMTCT services, thereby reducing some of the most pressing health problems facing women and their children in sub-Saharan Africa.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001295.
The United Nations Children's Fund (UNICEF) provides information on maternal mortality, including the WHO/UNICEF/UNFPA/World Bank 2008 country estimates of maternal mortality; a UNICEF special report tells the stories of seven mothers living with HIV in Lesotho
The World Health Organization provides information on maternal health, including information about Millennium Development Goal 5, which aims to reduce maternal mortality (in several languages); the Millennium Development Goals, which were agreed by world leaders in 2000, are designed to eradicate extreme poverty worldwide by 2015
Immpact is a global research initiative for the evaluation of safe motherhood intervention strategies
Maternal Death: The Avoidable Crisis is a briefing paper published by the independent humanitarian medical aid organization Médecins Sans Frontières (MSF) in March 2012
Information is available from Avert, an international AIDS charity on all aspects of HIV/AIDS, including information on women, HIV and AIDS, on HIV and pregnancy, on HIV and AIDS stigma and discrimination, and on HIV in Kenya (in English and Spanish); Avert also has personal stories from women living with HIV
The Stigma Action Network (SAN) is a collaborative endeavor that aims to comprehensively coordinate efforts to develop and expand program, research, and advocacy strategies for reducing HIV stigma worldwide, including mobilizing stakeholders, delivering program and policy solutions, and maximizing investments in HIV programs and services globally
The People Living with Stigma Index aims to address stigma relating to HIV and advocate on key barriers and issues perpetuating stigma; it has recently published Piecing it together for women and girls, the gender dimensions of HIV-related stigma
The Health Policy Project http://www.healthpolicyproject.com has prepared a review of the academic and programmatic literature on stigma and discrimination as barriers to achievement of global goals for maternal health and the elimination of new child HIV infections (see under Resources)
More information on the MAMAS study is available from the UCSF Center for AIDS Prevention Studies
doi:10.1371/journal.pmed.1001295
PMCID: PMC3424253  PMID: 22927800
17.  The Potential Impact of Male Circumcision on HIV in Sub-Saharan Africa 
PLoS Medicine  2006;3(7):e262.
Background
A randomized controlled trial (RCT) has shown that male circumcision (MC) reduces sexual transmission of HIV from women to men by 60% (32%−76%; 95% CI) offering an intervention of proven efficacy for reducing the sexual spread of HIV. We explore the implications of this finding for the promotion of MC as a public health intervention to control HIV in sub-Saharan Africa.
Methods and Findings
Using dynamical simulation models we consider the impact of MC on the relative prevalence of HIV in men and women and in circumcised and uncircumcised men. Using country level data on HIV prevalence and MC, we estimate the impact of increasing MC coverage on HIV incidence, HIV prevalence, and HIV-related deaths over the next ten, twenty, and thirty years in sub-Saharan Africa. Assuming that full coverage of MC is achieved over the next ten years, we consider three scenarios in which the reduction in transmission is given by the best estimate and the upper and lower 95% confidence limits of the reduction in transmission observed in the RCT.
MC could avert 2.0 (1.1−3.8) million new HIV infections and 0.3 (0.1−0.5) million deaths over the next ten years in sub-Saharan Africa. In the ten years after that, it could avert a further 3.7 (1.9−7.5) million new HIV infections and 2.7 (1.5−5.3) million deaths, with about one quarter of all the incident cases prevented and the deaths averted occurring in South Africa. We show that a) MC will increase the proportion of infected people who are women from about 52% to 58%; b) where there is homogenous mixing but not all men are circumcised, the prevalence of infection in circumcised men is likely to be about 80% of that in uncircumcised men; c) MC is equivalent to an intervention, such as a vaccine or increased condom use, that reduces transmission in both directions by 37%.
Conclusions
This analysis is based on the result of just one RCT, but if the results of that trial are confirmed we suggest that MC could substantially reduce the burden of HIV in Africa, especially in southern Africa where the prevalence of MC is low and the prevalence of HIV is high. While the protective benefit to HIV-negative men will be immediate, the full impact of MC on HIV-related illness and death will only be apparent in ten to twenty years.
Editors' Summary
Background.
Africa is the continent most affected by HIV/AIDS, and it is important to consider all possible means of reducing the spread of HIV infection. Male circumcision has been a tradition in many parts of Africa for hundreds of years. Boys who are circumcised usually have it done in late childhood or their early teenage years. It was noticed some years ago that those African groups in which circumcision is routinely done on all boys have fewer cases of HIV/AIDS than are found in groups where circumcision is not a tradition. This finding gave rise to the idea that circumcision might give a degree of protection against HIV, though it was recognised that some other, unknown difference between these groups of people might actually be the important factor. In 2005 a trial was reported from the Orange Farm area of South Africa, in which uncircumcised men were offered the chance to be circumcised. The men who agreed were divided at random into those who had the operation straightaway and those who were to have it two years later. During the next 18 months, the number of new cases of HIV infection was much higher amongst the men who had not been circumcised. Circumcision did therefore seem to offer a measure of protection against infection. This protective effect was estimated at being about 60%. Similar trials are under way in other parts of Africa but there are no results available from them at this stage.
Why Was This Study Done?
If the level of effectiveness of circumcision suggested by the South African trial is correct, then, as one part of a range of measures to reduce the spread of HIV, it would seem logical to encourage the practice of male circumcision. It would be useful to have an estimate of just how many new cases could be prevented and how many lives would be saved by the promotion of male circumcision. Calculations would have to allow for various factors, such as the present level of HIV infection, which varies from one country to another, and the fact that many men are already circumcised.
What Did the Researchers Do and Find?
This research did not involve collecting any new data. The researchers used mathematical modelling to make calculations. They based their model on data from the Orange Farm trial and on information from various sub-Saharan African countries on the proportion of men who are circumcised and the proportion who are HIV-positive. They made the assumption that if circumcision is intensively promoted, all men in those countries will be circumcised in 10 years time. They calculated the number of new cases that would be prevented and the lives that would be saved in ten years, 20 years, and 30 years time. Their best estimate is that with the promotion of male circumcision, two million cases and 0.3 million deaths will be avoided in ten years time. Over the following ten years, according to the researchers' model, a further 3.7 million cases and 2.7 million deaths would be prevented. Most of the initial impact would be in men, but the reduction in the number of HIV-positive men would in time also lower the risk of women becoming infected. Overall, on the basis of these calculations, male circumcision would reduce the rate of infections by about 37%—both female-to-male and male-to-female transmission. The size of the impact would vary from one country to another; it would be greatest in southern Africa where HIV infection rates are high and circumcision rates relatively low compared with the rest of sub-Saharan Africa.
What Do These Findings Mean?
Male circumcision alone cannot bring the HIV/AIDS epidemic in Africa under control. Even circumcised men can become infected, though their risk of doing so is much lower. However, the researchers call for the promotion of male circumcision to become a major part of AIDS control programmes. Their results are based on the findings of just one study (the Orange Farm trial), and it will be important to repeat the calculations when further studies have been completed.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0030262:
• The Orange Farm trial was published in PLoS Medicine. Several articles discussing the trial were also published in the same issue of the journal
• The Joint United Nations Programme on HIV/AIDS (UNAIDS) has information about the state of the HIV/AIDS epidemic and prevention strategies worldwide. It produces an annual report and has documents on a wide range of topics
•  AEGIS is the world's largest searchable database on HIV and AIDS.
• Many organizations provide information on AIDS prevention—for example, the Terrence Higgins Trust
• The World Bank's Global HIV/AIDS Program has a report about male circumcision and HIV infection
A modelling study, based on one trial plus national figures for current prevalence of HIV and of male circumcision (MC), found increasing MC in Africa could produce major fall in HIV prevalence in 10-12 years.
doi:10.1371/journal.pmed.0030262
PMCID: PMC1489185  PMID: 16822094
18.  Association Between Hepatitis C Virus Coinfection and Regional Adipose Tissue Volume in HIV-Infected Men and Women 
Objective
Coinfection with hepatitis C virus (HCV) is reported to be associated with a higher prevalence of lipodystrophy than HIV infection alone. We examine the association between HCV and adipose tissue volume in HIV-infected men and women.
Methods
Cross-sectional analysis of HIV-infected subjects from the study of Fat Redistribution and Metabolic Change in HIV Infection. MRI measured regional adipose tissue volume. Detectable HCV RNA defined HCV infection.
Results
Twenty percent of 792 men and 26% of 329 women were HIV/HCV-coinfected. HIV/HCV-coinfected and HIV-monoinfected women had similar amounts of subcutaneous adipose tissue (SAT) in the leg, lower trunk, upper trunk, and arm and similar amounts of visceral adipose tissue (VAT). Similar findings were seen in men, except in the leg and VAT. After adjustment, HCV infection remained associated with more leg fat in men (12.2%, 95% confidence interval [CI]: 0.3 to 25.3; P = 0.043). Among those on stavudine, HIV-monoinfected men had less leg fat (−7% effect per year of stavudine use, 95% CI: −9 to −5; P < 0.001); a weaker association was seen in HIV/HCV-coinfected men (−2% effect, 95% CI: −7 to 3; P = 0.45). Indinavir was associated with less leg fat (−4% in HIV-monoinfected men, 95% CI: −6 to −1; P = 0.002; −5% in HIV/HCV-coinfected men, 95% CI: −11 to 2; P = 0.14).
Conclusions
Our findings suggest that HIV/HCV coinfection is not associated with less SAT in men and women. HCV infection seems to mitigate the loss of leg fat seen in HIV-infected men on stavudine.
doi:10.1097/QAI.0b013e3180423a95
PMCID: PMC3164885  PMID: 17356466
adipose tissue volume; fat distribution; hepatitis C virus; HIV; lipodystrophy
19.  Risk Factors and Outcomes for Late Presentation for HIV-Positive Persons in Europe: Results from the Collaboration of Observational HIV Epidemiological Research Europe Study (COHERE) 
PLoS Medicine  2013;10(9):e1001510.
Amanda Mocroft and colleagues investigate risk factors and health outcomes associated with diagnosis at a late stage of infection in individuals across Europe.
Please see later in the article for the Editors' Summary
Background
Few studies have monitored late presentation (LP) of HIV infection over the European continent, including Eastern Europe. Study objectives were to explore the impact of LP on AIDS and mortality.
Methods and Findings
LP was defined in Collaboration of Observational HIV Epidemiological Research Europe (COHERE) as HIV diagnosis with a CD4 count <350/mm3 or an AIDS diagnosis within 6 months of HIV diagnosis among persons presenting for care between 1 January 2000 and 30 June 2011. Logistic regression was used to identify factors associated with LP and Poisson regression to explore the impact on AIDS/death. 84,524 individuals from 23 cohorts in 35 countries contributed data; 45,488 were LP (53.8%). LP was highest in heterosexual males (66.1%), Southern European countries (57.0%), and persons originating from Africa (65.1%). LP decreased from 57.3% in 2000 to 51.7% in 2010/2011 (adjusted odds ratio [aOR] 0.96; 95% CI 0.95–0.97). LP decreased over time in both Central and Northern Europe among homosexual men, and male and female heterosexuals, but increased over time for female heterosexuals and male intravenous drug users (IDUs) from Southern Europe and in male and female IDUs from Eastern Europe. 8,187 AIDS/deaths occurred during 327,003 person-years of follow-up. In the first year after HIV diagnosis, LP was associated with over a 13-fold increased incidence of AIDS/death in Southern Europe (adjusted incidence rate ratio [aIRR] 13.02; 95% CI 8.19–20.70) and over a 6-fold increased rate in Eastern Europe (aIRR 6.64; 95% CI 3.55–12.43).
Conclusions
LP has decreased over time across Europe, but remains a significant issue in the region in all HIV exposure groups. LP increased in male IDUs and female heterosexuals from Southern Europe and IDUs in Eastern Europe. LP was associated with an increased rate of AIDS/deaths, particularly in the first year after HIV diagnosis, with significant variation across Europe. Earlier and more widespread testing, timely referrals after testing positive, and improved retention in care strategies are required to further reduce the incidence of LP.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Every year about 2.5 million people become newly infected with HIV, the virus that causes AIDS. HIV can be transmitted through unprotected sex with an infected partner, from an HIV-positive mother to her unborn baby, or through injection of drugs. Most people do not become ill immediately after infection with HIV although some develop a short influenza-like illness. The next stage of the HIV infection, which may last up to 10 years, also has no major symptoms but, during this stage, HIV slowly destroys immune system cells, including CD4 cells, a type of lymphocyte. Eventually, when the immune system is unable to fight off infections by other disease-causing organisms, HIV-positive people develop AIDS-defining conditions—unusual viral, bacterial, and fungal infections and unusual tumors. Progression to AIDS occurs when any severe AIDS-defining condition is diagnosed, when the CD4 count in the blood falls below 200 cells/mm3, or when CD4 cells account for fewer than 15% of lymphocytes.
Why Was This Study Done?
People need to know they are HIV positive as soon as possible after they become infected because antiretroviral therapy, which controls but does not cure HIV infection, works best if it is initiated when people still have a relatively high CD4 count. Early diagnosis also reduces the risk of onward HIV transmission. However, 40%–60% of HIV-positive individuals in developed countries are not diagnosed until they have a low CD4 count or an AIDS-defining illness. Reasons for such late presentation include fear of discrimination or stigmatization, limited knowledge about HIV risk factors, testing, and treatment together with missed opportunities to offer an HIV test. Policy makers involved in national and international HIV control programs need detailed information about patterns of late presentation before they can make informed decisions about how to reduce this problem. In this study, therefore, the researchers use data collected by the Collaboration of Observational HIV Epidemiological Research in Europe (COHERE) to analyze trends in late presentation over time across Europe and in different groups of people at risk of HIV infection and to investigate the clinical consequences of late presentation.
What Did the Researchers Do and Find?
The researchers analyzed data collected from 84,524 individuals participating in more than 20 observational studies that were undertaken in 35 European countries and that investigated outcomes among HIV-positive people. Nearly 54% of the participants were late presenters—individuals who had a CD4 count of less than 350 cells/mm3 or an AIDS-defining illness within 6 months of HIV diagnosis. Late presentation was highest among heterosexual males, in Southern European countries, and among people originating in Africa. Overall, late presentation decreased from 57.3% in 2000 to 51.7% in 2010/11. However, whereas late presentation decreased over time among men having sex with men in Central and Northern Europe, for example, it increased over time among female heterosexuals in Southern Europe. Finally, among the 8,000 individuals who developed a new AIDS-defining illness or died during follow-up, compared to non-late presentation, late presentation was associated with an increased incidence of AIDS/death in all regions of Europe during the first and second year after HIV diagnosis (but not in later years); the largest increase in incidence (13-fold) occurred during the first year after diagnosis in Southern Europe.
What Do These Findings Mean?
These findings indicate that, although late presentation with HIV infection has decreased in recent years, it remains an important issue across Europe and in all groups of people at risk of HIV infection. They also show that individuals presenting late have a worse clinical outlook, particularly in the first and second year after diagnosis compared to non-late presenters. Several aspects of the study design may affect the accuracy and usefulness of these findings, however. For example, some of the study participants recorded as late presenters may have been people who were aware of their HIV status but who chose not to seek care for HIV infection, or may have been seen in the health care system prior to HIV diagnosis without being offered an HIV test. Delayed entry into care and late presentation are likely to have different risk factors, a possibility that needs to be studied further. Despite this and other study limitations, these findings nevertheless suggest that HIV testing strategies that encourage early testing in all populations at risk, that ensure timely referrals, and that improve retention in care are required to further reduce the incidence of late presentation with HIV infection in Europe.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/ 10.1371/journal.pmed.1001510.
Information is available from the US National Institute of Allergy and infectious diseases on HIV infection and AIDS
NAM/aidsmap provides basic information about HIV/AIDS, and summaries of recent research findings on HIV care and treatment
Information is available from Avert, an international AIDS charity, on many aspects of HIV/AIDS, including detailed information on the stages of HIV infection and on HIV and AIDS in Europe (in English and Spanish)
The HIV in Europe Initiative has information about strategies to improve earlier diagnosis and access to care in Europe
Information about COHERE, which was established in 2005 to conduct epidemiological research on the prognosis and outcome of HIV-infected people from across Europe, is available; more information on the consensus definition of late presentation used in this study is available through the HIV in Europe initiative
Patient stories about living with HIV/AIDS are available through Avert and through the nonprofit website Healthtalkonline
doi:10.1371/journal.pmed.1001510
PMCID: PMC3796947  PMID: 24137103
20.  Prevalence of Consensual Male–Male Sex and Sexual Violence, and Associations with HIV in South Africa: A Population-Based Cross-Sectional Study 
PLoS Medicine  2013;10(6):e1001472.
Using a method that offered complete privacy to participants, Rachel Jewkes and colleagues conducted a survey among South African men about their lifetime same-sex experiences.
Please see later in the article for the Editors' Summary
Background
In sub-Saharan Africa the population prevalence of men who have sex with men (MSM) is unknown, as is the population prevalence of male-on-male sexual violence, and whether male-on-male sexual violence may relate to HIV risk. This paper describes lifetime prevalence of consensual male–male sexual behavior and male-on-male sexual violence (victimization and perpetration) in two South African provinces, socio-demographic factors associated with these experiences, and associations with HIV serostatus.
Methods and Findings
In a cross-sectional study conducted in 2008, men aged 18–49 y from randomly selected households in the Eastern Cape and KwaZulu-Natal provinces provided anonymous survey data and dried blood spots for HIV serostatus assessment. Interviews were completed in 1,737 of 2,298 (75.6%) of enumerated and eligible households. From these households, 1,705 men (97.1%) provided data on lifetime history of same-sex experiences, and 1,220 (70.2%) also provided dried blood spots for HIV testing. 5.4% (n = 92) of participants reported a lifetime history of any consensual sexual activity with another man; 9.6% (n = 164) reported any sexual victimization by a man, and 3.0% (n = 51) reported perpetrating sexual violence against another man. 85.0% (n = 79) of men with a history of consensual sex with men reported having a current female partner, and 27.7% (n = 26) reported having a current male partner. Of the latter, 80.6% (n = 21/26) also reported having a female partner. Men reporting a history of consensual male–male sexual behavior are more likely to have been a victim of male-on-male sexual violence (adjusted odds ratio [aOR] = 7.24; 95% CI 4.26–12.3), and to have perpetrated sexual violence against another man (aOR = 3.10; 95% CI 1.22–7.90). Men reporting consensual oral/anal sex with a man were more likely to be HIV+ than men with no such history (aOR = 3.11; 95% CI 1.24–7.80). Men who had raped a man were more likely to be HIV+ than non-perpetrators (aOR = 3.58; 95% CI 1.17–10.9).
Conclusions
In this sample, one in 20 men (5.4%) reported lifetime consensual sexual contact with a man, while about one in ten (9.6%) reported experience of male-on-male sexual violence victimization. Men who reported having had sex with men were more likely to be HIV+, as were men who reported perpetrating sexual violence towards other men. Whilst there was no direct measure of male–female concurrency (having overlapping sexual relationships with men and women), the data suggest that this may have been common. These findings suggest that HIV prevention messages regarding male–male sex in South Africa should be mainstreamed with prevention messages for the general population, and sexual health interventions and HIV prevention interventions for South African men should explicitly address male-on-male sexual violence.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
AIDS first emerged in the early 1980s among gay men living in the US, but it soon became clear that AIDS also infects heterosexual men and women. Now, three decades on, globally, 34 million people (two-thirds of whom live in sub-Saharan Africa and half of whom are women) are infected with HIV, the virus that causes AIDS, and 2.5 million people become infected every year. HIV is most often spread by having unprotected sex with an infected partner, and most sexual transmission of HIV now occurs during heterosexual sex. However, 5%–10% of all new HIV infections still occur in men who have sex with men (MSM; homosexual, bisexual, and transgender men, and heterosexual men who sometimes have consensual sex with men). Moreover, in the concentrated HIV epidemics of high-income countries (epidemics in which the prevalence of HIV infection is more than 5% in at-risk populations such as sex workers but less than 1% in the general population), male-to-male sexual contact remains the most important transmission route, and MSM often have a higher prevalence of HIV infection than heterosexual men.
Why Was This Study Done?
By contrast to high-income countries, HIV epidemics in sub-Saharan Africa are generalized—the prevalence of HIV infection is 1% or more in the general population. Because male-to-male sexual behavior is criminalized in many African countries and because homosexuality is widely stigmatized, little is known about the prevalence of consensual male–male sexual behavior in sub-Saharan Africa. This information and a better understanding of male–female sexual concurrency (having overlapping sexual relationships with men and women) and of how male-to-male transmission contributes to generalized HIV epidemics is needed to inform the design of HIV prevention strategies for use in sub-Saharan Africa. In addition, very little is known about male-on-male sexual violence. Such violence is potentially important to study because we know that male-on-female violence is associated with increased HIV risk for both victims and perpetrators. In this cross-sectional study (an investigation that measures population characteristics at a single time point), the researchers use data from a population-based household survey to investigate the lifetime prevalence of consensual male–male sexual behavior and male-on-male sexual violence (victimization and perpetration) among men in South Africa and the association of these experiences with HIV infection.
What Did the Researchers Do and Find?
About 1,700 adult men from randomly selected households in the Eastern Cape and KwaZulu-Natal provinces of South Africa self-completed a survey that included questions about their lifetime history of same-sex experiences using audio-enhanced personal digital assistants, a data collection method that provided a totally private and anonymous environment for the disclosure of illegal and stigmatized behavior; 1,220 of them also provided dried blood spots for HIV testing. Ninety-two men (5.4% of the participants) reported consensual sexual activity (for example, anal or oral sex) with another man at some time during their life; 9.6% of the men reported that they had been forced to have sex with another man (sexual victimization), and 3% reported that they had perpetrated sexual violence against another man. Most of the men who reported consensual sex with men, including those with current male partners, reported that they had a current female partner. Men with a history of consensual male–male sexual behavior were more likely to have been a victim or perpetrator of male-on-male sexual violence than men without a history of such experiences. Finally, men who reported consensual oral or anal sex with a man were more likely to be HIV+ than men without such a history, and perpetrators of male-on-male sexual violence were more likely to be HIV+ than non-perpetrators.
What Do These Findings Mean?
These findings provide new information about male–male sexual behaviors, male-on-male sexual violence, male–female concurrency, and HIV prevalence among men in two South African provinces. The precision of these findings is likely to be affected by the small numbers of men reporting a history of consensual male–male sexual behavior and of male-on-male sexual violence. Importantly, because the study was cross-sectional, these findings cannot indicate whether the association between consensual male–male sexual behaviors and increased risk of male-on-male sexual violence is causal. Moreover, these findings may not be generalizable to other regions of South Africa or to other African countries. Nevertheless, these findings suggest that information about the risks of male–male sexual behaviors should be included in HIV prevention strategies targeted at the general population in South Africa and that HIV prevention interventions for South African men should explicitly address male-on-male sexual violence. Similar HIV prevention strategies may also be suitable for other African countries, but are likely to succeed only in countries that have, like South Africa, decriminalized consensual homosexual behavior.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001472.
This study is further discussed in a PLOS Medicine Perspective by Jerome Singh
Information is available from the US National Institute of Allergy and Infectious Diseases on HIV infection and AIDS
NAM/aidsmap provides basic information about HIV/AIDS, including summaries of recent research findings on HIV care and treatment
Information is available from Avert, an international AIDS charity, on many aspects of HIV/AIDS, including information on HIV and men who have sex with men, on HIV prevention, and on AIDS in Africa (in English and Spanish)
The US Centers for Disease Control and Prevention also has information about HIV/AIDS among men who have sex with men (in English and Spanish)
Patient stories about living with HIV/AIDS are available through Avert; the charity website Healthtalkonline also provides personal stories about living with HIV
doi:10.1371/journal.pmed.1001472
PMCID: PMC3708702  PMID: 23853554
21.  Male Circumcision at Different Ages in Rwanda: A Cost-Effectiveness Study 
PLoS Medicine  2010;7(1):e1000211.
Agnes Binagwaho and colleagues predict that circumcision of newborn boys would be effective and cost-saving as a long-term strategy to prevent HIV in Rwanda.
Background
There is strong evidence showing that male circumcision (MC) reduces HIV infection and other sexually transmitted infections (STIs). In Rwanda, where adult HIV prevalence is 3%, MC is not a traditional practice. The Rwanda National AIDS Commission modelled cost and effects of MC at different ages to inform policy and programmatic decisions in relation to introducing MC. This study was necessary because the MC debate in Southern Africa has focused primarily on MC for adults. Further, this is the first time, to our knowledge, that a cost-effectiveness study on MC has been carried out in a country where HIV prevalence is below 5%.
Methods and Findings
A cost-effectiveness model was developed and applied to three hypothetical cohorts in Rwanda: newborns, adolescents, and adult men. Effectiveness was defined as the number of HIV infections averted, and was calculated as the product of the number of people susceptible to HIV infection in the cohort, the HIV incidence rate at different ages, and the protective effect of MC; discounted back to the year of circumcision and summed over the life expectancy of the circumcised person. Direct costs were based on interviews with experienced health care providers to determine inputs involved in the procedure (from consumables to staff time) and related prices. Other costs included training, patient counselling, treatment of adverse events, and promotion campaigns, and they were adjusted for the averted lifetime cost of health care (antiretroviral therapy [ART], opportunistic infection [OI], laboratory tests). One-way sensitivity analysis was performed by varying the main inputs of the model, and thresholds were calculated at which each intervention is no longer cost-saving and at which an intervention costs more than one gross domestic product (GDP) per capita per life-year gained. Results: Neonatal MC is less expensive than adolescent and adult MC (US$15 instead of US$59 per procedure) and is cost-saving (the cost-effectiveness ratio is negative), even though savings from infant circumcision will be realized later in time. The cost per infection averted is US$3,932 for adolescent MC and US$4,949 for adult MC. Results for infant MC appear robust. Infant MC remains highly cost-effective across a reasonable range of variation in the base case scenario. Adolescent MC is highly cost-effective for the base case scenario but this high cost-effectiveness is not robust to small changes in the input variables. Adult MC is neither cost-saving nor highly cost-effective when considering only the direct benefit for the circumcised man.
Conclusions
The study suggests that Rwanda should be simultaneously scaling up circumcision across a broad range of age groups, with high priority to the very young. Infant MC can be integrated into existing health services (i.e., neonatal visits and vaccination sessions) and over time has better potential than adolescent and adult circumcision to achieve the very high coverage of the population required for maximal reduction of HIV incidence. In the presence of infant MC, adolescent and adult MC would evolve into a “catch-up” campaign that would be needed at the start of the program but would eventually become superfluous.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Acquired immunodeficiency syndrome (AIDS) has killed more than 25 million people since 1981 and more than 31 million people (22 million in sub-Saharan Africa alone) are now infected with the human immunodeficiency virus (HIV), which causes AIDS. There is no cure for HIV/AIDS and no vaccine against HIV infection. Consequently, prevention of HIV transmission is extremely important. HIV is most often spread through unprotected sex with an infected partner. Individuals can reduce their risk of HIV infection, therefore, by abstaining from sex, by having one or a few sexual partners, and by always using a male or female condom. In addition, male circumcision—the removal of the foreskin, the loose fold of skin that covers the head of penis—can halve HIV transmission rates to men resulting from sex with women. Thus, as part of its HIV prevention strategy, the World Health Organization (WHO) recommends that male circumcision programs be scaled up in countries where there is a generalized HIV epidemic and where few men are circumcised.
Why Was This Study Done?
One such country is Rwanda. Here, 3% of the adult population is infected with HIV but only 15% of men are circumcised—worldwide, about 30% of men are circumcised. Demand for circumcision is increasing in Rwanda but, before policy makers introduce a country-wide male circumcision program, they need to identify the most cost-effective way to increase circumcision rates. In particular, they need to decide the age at which circumcision should be offered. Circumcision soon after birth (neonatal circumcision) is quick and simple and rarely causes any complications. Circumcision of adolescents and adults is more complex and has a higher complication rate. Although several studies have investigated the cost-effectiveness (the balance between the clinical and financial costs of a medical intervention and its benefits) of circumcision in adult men, little is known about its cost-effectiveness in newborn boys. In this study, which is one of several studies on male circumcision being organized by the National AIDS Control Commission in Rwanda, the researchers model the cost-effectiveness of circumcision at different ages.
What Did the Researchers Do and Find?
The researchers developed a simple cost-effectiveness model and applied it to three hypothetical groups of Rwandans: newborn boys, adolescent boys, and adult men. For their model, the researchers calculated the effectiveness of male circumcision (the number of HIV infections averted) by estimating the reduction in the annual number of new HIV infections over time. They obtained estimates of the costs of circumcision (including the costs of consumables, staff time, and treatment of complications) from health care providers and adjusted these costs for the money saved through not needing to treat HIV in males in whom circumcision prevented infection. Using their model, the researchers estimate that each neonatal male circumcision would cost US$15 whereas each adolescent or adult male circumcision would cost US$59. Neonatal male circumcision, they report, would be cost-saving. That is, over a lifetime, neonatal male circumcision would save more money than it costs. Finally, using the WHO definition of cost-effectiveness (for a cost-effective intervention, the additional cost incurred to gain one year of life must be less than a country's per capita gross domestic product), the researchers estimate that, although adolescent circumcision would be highly cost-effective, circumcision of adult men would only be potentially cost-effective (but would likely prove cost-effective if the additional infections that would occur from men to their partners without a circumcision program were also taken into account).
What Do These Findings Mean?
As with all modeling studies, the accuracy of these findings depends on the many assumptions included in the model. However, the findings suggest that male circumcision for infants for the prevention of HIV infection later in life is highly cost-effective and likely to be cost-saving and that circumcision for adolescents is cost-effective. The researchers suggest, therefore, that policy makers in Rwanda and in countries with similar HIV infection and circumcision rates should scale up male circumcision programs across all age groups, with high priority being given to the very young. If infants are routinely circumcised, they suggest, circumcision of adolescent and adult males would become a “catch-up” campaign that would be needed at the start of the program but that would become superfluous over time. Such an approach would represent a switch from managing the HIV epidemic as an emergency towards focusing on sustainable, long-term solutions to this major public-health problem.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000211.
This study is further discussed in a PLoS Medicine Perspective by Seth Kalichman
Information is available from the US National Institute of Allergy and Infectious Diseases on HIV infection and AIDS
Information is available from the Joint United Nations Programme on HIV/AIDS (UNAIDS) on HIV infection and AIDS and on male circumcision in relation to HIV and AIDS
HIV InSite has comprehensive information on all aspects of HIV/AIDS
Information is available from Avert, an international AIDS charity on many aspects of HIV/AIDS, including information on HIV and AIDS in Africa, and on circumcision and HIV (some information in English and Spanish)
More information about male circumcision is available from the Clearinghouse on Male Circumcision
The National AIDS Control Commission of Rwanda provides detailed information about HIV/AIDS in Rwanda (in English and French)
doi:10.1371/journal.pmed.1000211
PMCID: PMC2808207  PMID: 20098721
22.  Prospective Evaluation of Bone Mineral Density among Middle-Aged HIV-Infected and Uninfected Women: Association between Methadone Use and Bone Loss 
Maturitas  2011;70(3):295-301.
Objective
We undertook a prospective study to assess the impact of HIV infection on BMD in a cohort of HIV-infected and uninfected women that included illicit drug users, and to measure the contribution of traditional risk factors as well as HIV-related factors to loss of BMD over time.
Methods
We analyzed BMD at baseline and after ≥18 months in 245 middle-aged HIV-infected and 219 uninfected women, and conducted linear regression analysis to determine factors associated with annual BMD change at the femoral neck, total hip and lumbar spine.
Results
HIV-infected women had lower baseline BMD at the femoral neck and total hip compared with controls; unadjusted rates of BMD change did not differ by HIV status at any site. In multivariable analyses, we found that HIV seropositivity without protease inhibitor (PI) use was associated with BMD decline at the lumbar spine (−.009 gm/cm2 per year, p=.03.) Additional factors associated with BMD decline were: postmenopausal status, lower BMI, and methadone use at the lumbar spine; postmenopausal status and hepatitis C seropositivity at the femoral neck; and postmenopausal status, age, smoking, and lower BMI at the total hip (all p<.05). Among HIV-infected women, ≥3 years of PI use was associated with an increase in lumbar spine BMD (.013 gm/cm2 per year, p=.008.)
Conclusions
Bone loss among HIV–infected middle-aged women was modest, and possibly mitigated by PI use. Methadone use was associated with BMD decline, and should be considered when evaluating women for osteoporosis risk.
doi:10.1016/j.maturitas.2011.08.003
PMCID: PMC3189307  PMID: 21944566
osteopenia; osteoporosis; bone mineral density; HIV; women
23.  Intermittent Preventive Treatment of Malaria in Pregnancy with Mefloquine in HIV-Infected Women Receiving Cotrimoxazole Prophylaxis: A Multicenter Randomized Placebo-Controlled Trial 
PLoS Medicine  2014;11(9):e1001735.
Clara Menéndez and colleagues conducted a randomized controlled trial among HIV-positive pregnant women in Kenya, Mozambique, and Tanzania to investigate the safety and efficacy of mefloquine as intermittent preventative therapy for malaria in women receiving cotrimoxazole prophylaxis and long-lasting insecticide treated nets.
Please see later in the article for the Editors' Summary
Background
Intermittent preventive treatment in pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP) is recommended for malaria prevention in HIV-negative pregnant women, but it is contraindicated in HIV-infected women taking daily cotrimoxazole prophylaxis (CTXp) because of potential added risk of adverse effects associated with taking two antifolate drugs simultaneously. We studied the safety and efficacy of mefloquine (MQ) in women receiving CTXp and long-lasting insecticide treated nets (LLITNs).
Methods and Findings
A total of 1,071 HIV-infected women from Kenya, Mozambique, and Tanzania were randomized to receive either three doses of IPTp-MQ (15 mg/kg) or placebo given at least one month apart; all received CTXp and a LLITN. IPTp-MQ was associated with reduced rates of maternal parasitemia (risk ratio [RR], 0.47 [95% CI 0.27–0.82]; p = 0.008), placental malaria (RR, 0.52 [95% CI 0.29–0.90]; p = 0.021), and reduced incidence of non-obstetric hospital admissions (RR, 0.59 [95% CI 0.37–0.95]; p = 0.031) in the intention to treat (ITT) analysis. There were no differences in the prevalence of adverse pregnancy outcomes between groups. Drug tolerability was poorer in the MQ group compared to the control group (29.6% referred dizziness and 23.9% vomiting after the first IPTp-MQ administration). HIV viral load at delivery was higher in the MQ group compared to the control group (p = 0.048) in the ATP analysis. The frequency of perinatal mother to child transmission of HIV was increased in women who received MQ (RR, 1.95 [95% CI 1.14–3.33]; p = 0.015). The main limitation of the latter finding relates to the exploratory nature of this part of the analysis.
Conclusions
An effective antimalarial added to CTXp and LLITNs in HIV-infected pregnant women can improve malaria prevention, as well as maternal health through reduction in hospital admissions. However, MQ was not well tolerated, limiting its potential for IPTp and indicating the need to find alternatives with better tolerability to reduce malaria in this particularly vulnerable group. MQ was associated with an increased risk of mother to child transmission of HIV, which warrants a better understanding of the pharmacological interactions between antimalarials and antiretroviral drugs.
Trial registration
ClinicalTrials.gov NCT 00811421; Pan African Clinical Trials Registry PACTR 2010020001813440
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Malaria, a mosquito-borne parasitic disease, kills about 600,000 people every year. Most of these deaths occur among young children living in sub-Saharan Africa but pregnant women living in Africa are also very vulnerable to malaria. Infection with malaria during pregnancy can cause severe maternal anemia (reduced red blood cell numbers), stillbirths, and pre-term and low-birthweight babies, and is responsible for the deaths of many African women and their babies. To reduce the loss of life from malaria in pregnancy, the World Health Organization (WHO) recommends that pregnant women living in Africa receive the antimalarial drug sulfadoxine-pyrimethamine (SP) at each scheduled antenatal care visit given at least a month apart (intermittent preventive treatment in pregnancy [IPTp]). In addition, WHO advises pregnant women to sleep under insecticide-treated bed nets to protect themselves from the bites of infected mosquitoes and recommends effective case management of pregnant women with malarial illness.
Why Was This Study Done?
Pregnant women living in Africa are often infected with HIV, the virus that causes AIDS. HIV infection increases both the risk and severity of malaria infection during pregnancy, and at least one million pregnancies are complicated by co-infection with malaria and HIV in sub-Saharan Africa every year. WHO recommends that HIV-positive pregnant women take cotrimoxazole (CTX) daily to prevent opportunistic infections (CTX prophylaxis [CTXp]). Unfortunately, both CTX and SP are antifolate drugs and taking two drugs of this type increases a woman's risk of developing a severe skin reaction. Moreover, although CTXp protects children and HIV-infected adults against malaria, it is not known whether CTXp alone protects HIV-infected pregnant women adequately against malaria. Thus, evaluations of alternative drugs for use in IPTp in HIV-positive pregnant women are needed. In this randomized placebo-controlled trial, the researchers study the safety and efficacy of the antimalarial drug mefloquine (MQ) in HIV-infected women receiving CTXp. A randomized, placebo-controlled trial compares outcomes among people chosen through the play of chance to receive either the drug under investigation or a “dummy” (placebo) drug.
What Did the Researchers Do and Find?
The researchers allocated 1,071 HIV-infected pregnant women from Kenya, Mozambique, and Tanzania to receive three doses of MQ (IPTp-MQ), given at least one month apart, or three doses of placebo. All the women received CTXp and were given an insecticide-treated bed net. In an intention-to-treat analysis (an analysis that considers the outcomes of all trial participants irrespective of whether they receive their allocated treatment), the prevalence of parasitemia (parasites in the blood) at delivery among women given IPTp-MQ was 3.5% whereas the prevalence among women given the placebo was 6.9%. In other words, compared to placebo, IPTp-MQ was associated with a reduced risk of maternal parasitemia. IPTp-MQ was also associated with a reduced rate of placental malaria (parasites in the placenta) and a reduced incidence of hospital admissions for non-pregnancy related causes. There was no difference in adverse pregnancy outcomes such as stillbirth between the intervention groups but drug tolerability was poorer in the MQ group than in the placebo group. Finally, in an exploratory (unplanned) according-to-protocol analysis (an analysis that only considers outcomes in trial participants who receive their allocated intervention), women in the MQ group had a higher HIV viral load at delivery than women in the control group and were nearly twice as likely to transmit HIV to their child around the time of birth.
What Do These Findings Mean?
These findings suggest that the addition of IPTp-MQ to CTXp and the use of insecticide-treated bed nets can improve malaria prevention and maternal health in HIV-infected pregnant women in Africa. However, the poor tolerability of MQ and the association of MQ treatment with both an increased HIV viral load at delivery and a higher frequency of mother-to-child-transmission of HIV when compared to placebo raise concerns about the use of MQ in IPTp. Because these last two findings came from an exploratory analysis, which is more likely to throw up a chance finding than a pre-planned analysis further studies are needed to confirm these unexpected but potentially important findings. Nevertheless, overall, the findings of this study suggest that MQ should not be recommended for IPTp in HIV-infected pregnant women in Africa and highlight the need to find alternative drugs for malaria prevention in this group of women who are particularly vulnerable to malaria.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001735.
This study is further discussed in a PLOS Medicine Perspective by Richard Steketee.
A related PLOS Medicine Research Article by González et al. compares the efficacy of IPTp-MQ and IPTp-SP in HIV-negative women
Information is available from the World Health Organization on malaria (in several languages) and on malaria in pregnancy; information on IPTp and the current WHO policy recommendation on IPTp with SP are available; the 2013 World Malaria Report provides details of the current global malaria situation
The US Centers for Disease Control and Prevention also provides information on malaria; a personal story about malaria in pregnancy is available
Information is available from the Roll Back Malaria Partnership on all aspects of global malaria control, including information on malaria in pregnancy
The Malaria in Pregnancy Consortium is undertaking research into the prevention and treatment of malaria in pregnancy
MedlinePlus provides links to additional information on malaria (in English and Spanish)
More information about the trial protocol is available
doi:10.1371/journal.pmed.1001735
PMCID: PMC4172537  PMID: 25247995
24.  Impact of Antiretroviral Therapy on Incidence of Pregnancy among HIV-Infected Women in Sub-Saharan Africa: A Cohort Study 
PLoS Medicine  2010;7(2):e1000229.
A multicountry cohort study in sub-Saharan Africa by Landon Myer and colleagues reveals higher pregnancy rates in HIV-infected women on antiretroviral therapy (ART).
Background
With the rapid expansion of antiretroviral therapy (ART) services in sub-Saharan Africa there is growing recognition of the importance of fertility and childbearing among HIV-infected women. However there are few data on whether ART initiation influences pregnancy rates.
Methods and Findings
We analyzed data from the Mother-to-Child Transmission-Plus (MTCT-Plus) Initiative, a multicountry HIV care and treatment program for women, children, and families. From 11 programs in seven African countries, women were enrolled into care regardless of HIV disease stage and followed at regular intervals; ART was initiated according to national guidelines on the basis of immunological and/or clinical criteria. Standardized forms were used to collect sociodemographic and clinical data, including incident pregnancies. Overall 589 incident pregnancies were observed among the 4,531 women included in this analysis (pregnancy incidence, 7.8/100 person-years [PY]). The rate of new pregnancies was significantly higher among women receiving ART (9.0/100 PY) compared to women not on ART (6.5/100 PY) (adjusted hazard ratio, 1.74; 95% confidence interval, 1.19–2.54). Other factors independently associated with increased risk of incident pregnancy included younger age, lower educational attainment, being married or cohabiting, having a male partner enrolled into the program, failure to use nonbarrier contraception, and higher CD4 cell counts.
Conclusions
ART use is associated with significantly higher pregnancy rates among HIV-infected women in sub-Saharan Africa. While the possible behavioral or biomedical mechanisms that may underlie this association require further investigation, these data highlight the importance of pregnancy planning and management as a critical but neglected component of HIV care and treatment services.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Human immunodeficiency virus (HIV) causes Acquired Immunodeficiency Syndrome (AIDS), which is a major global cause of disease and death. More than 33 million people around the world are infected with HIV, with nearly 5,500 dying daily from HIV and AIDS-related complications. HIV/AIDS is especially problematic in sub-Saharan Africa, where it is the leading cause of death. There is no cure for HIV/AIDS, but medicines known as “antiretroviral therapy” (ART) can prolong life and reduce complications in patients infected with HIV. 97% of patients with HIV/AIDS live in low- and middle-income countries. According to the World Health Organization, nearly 10 million of these patients need ART. As patients' access to treatment is often hindered by the high cost and low availability of ART, global health efforts have focused on promoting ART use in resource-limited nations. Such efforts also increase awareness of how HIV is spread (contact with blood or semen, in sexual intercourse, sharing needles, or from mother to child during childbirth). ART reduces, but does not remove, the chance of a mother's passing HIV to her child during birth.
Why Was This Study Done?
By the end of 2007, 3 million HIV-infected patients in poor countries were receiving ART. Many of those treated with ART are young women of child-bearing age. Childbirth is an important means of spreading HIV in sub-Saharan Africa, where 60% of all HIV patients are women. This study questions whether the improved health and life expectancy that results from treatment with ART affects pregnancy rates of HIV-infected patients. The study explores this question in seven African countries, by examining the rates of pregnancy in HIV-infected women before and after they started ART.
What Did the Researchers Do and Find?
The authors looked at the records of 4,531 HIV-infected women enrolled in the Mother-to-Child-Transmission-Plus (MTCT-Plus) Initiative in seven African countries. MTCT -Plus, begun in 2002, is a family-centered treatment program that offers regular checkups, blood tests, counseling, and ART treatment (if appropriate) to women and their families. At each checkup, women's CD4+ cell counts and World Health Organization guidelines were used to determine their eligibility for starting ART. Over a 4-year period, nearly a third of the women starting ART experienced a pregnancy: 244 pregnancies occurred in the “pre-ART” group (women not receiving ART) compared to 345 pregnancies in the “on-ART” group (women receiving ART). The chance of pregnancy increased over time in the on-ART group to almost 80% greater than the pre-ART group, while remaining relatively low and constant in the pre-ART group. The authors noted that, as expected, other factors also increased the chances of pregnancy, including younger age, lower educational status, and use of nonbarrier contraception such as injectable hormones.
What Do These Findings Mean?
This study suggests that starting ART is associated with higher pregnancy rates in sub-Saharan Africa, nearly doubling the chances of a woman becoming pregnant. The reasons for this link are unclear. One possible explanation is behavioral: women receiving ART may feel more motivated to have children as their health and quality of life improve. However, the study did not examine how pregnancy desires and sexual activity of women changed while on ART, and cannot discern why ART is linked to increased pregnancy. By using pregnancy data gathered from patient questionnaires rather than laboratory tests, the study is limited by the possibility of inaccurate patient reporting. Understanding how pregnancy rates vary in HIV-infected women receiving ART helps support the formation of responsive, effective HIV programs. Female HIV patients of child-bearing age, who form the majority of patients receiving ART in sub-Saharan Africa, would benefit from programs that combine starting HIV treatment with ART with education and contraception counseling and pregnancy-related care.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000229.
Information is available from the US National Institute of Allergy and Infectious Diseases on HIV infection and AIDS
HIV InSite has comprehensive information on all aspects of HIV/AIDS, including a list of articles and other sources of information about the primary care of adolescents with HIV
A UNAIDS 2008 report is available on the global AIDS epidemic
The International Planned Parenthood Foundation provides information on sexual and reproductive health and HIV
The International Center for AIDS Care and Treatment Programs at the Columbia University Mailman School of Public health provides information to assist HIV care and treatment programs in resource-limited settings
doi:10.1371/journal.pmed.1000229
PMCID: PMC2817715  PMID: 20161723
25.  Antiretroviral Pre-exposure Prophylaxis Prevents Vaginal Transmission of HIV-1 in Humanized BLT Mice 
PLoS Medicine  2008;5(1):e16.
Background
Worldwide, vaginal transmission now accounts for more than half of newly acquired HIV-1 infections. Despite the urgency to develop and implement novel approaches capable of preventing HIV transmission, this process has been hindered by the lack of adequate small animal models for preclinical efficacy and safety testing. Given the importance of this route of transmission, we investigated the susceptibility of humanized mice to intravaginal HIV-1 infection.
Methods and Findings
We show that the female reproductive tract of humanized bone marrow–liver–thymus (BLT) mice is reconstituted with human CD4+ T and other relevant human cells, rendering these humanized mice susceptible to intravaginal infection by HIV-1. Effects of HIV-1 infection include CD4+ T cell depletion in gut-associated lymphoid tissue (GALT) that closely mimics what is observed in HIV-1–infected humans. We also show that pre-exposure prophylaxis with antiretroviral drugs is a highly effective method for preventing vaginal HIV-1 transmission. Whereas 88% (7/8) of BLT mice inoculated vaginally with HIV-1 became infected, none of the animals (0/5) given pre-exposure prophylaxis of emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF) showed evidence of infection (Chi square = 7.5, df = 1, p = 0.006).
Conclusions
The fact that humanized BLT mice are susceptible to intravaginal infection makes this system an excellent candidate for preclinical evaluation of both microbicides and pre-exposure prophylactic regimens. The utility of humanized mice to study intravaginal HIV-1 transmission is particularly highlighted by the demonstration that pre-exposure prophylaxis can prevent intravaginal HIV-1 transmission in the BLT mouse model.
J. Victor Garcia and colleagues show that mice with immune systems reconstituted from human bone marrow, liver, and thymus transplants provide a model for prevention of intravaginal HIV infection.
Editors' Summary
Background.
Since the first cases of acquired immunodeficiency syndrome (AIDS) in 1981, the AIDS epidemic has spread rapidly. About 33 million people are now infected with the human immunodeficiency virus (HIV), the cause of AIDS. More than half of newly acquired infections now occur in women, mostly through unprotected vaginal sex with an infected male partner. Women are biologically more susceptible than men to HIV infection during vaginal intercourse and often cannot persuade their partner to use a condom. Consequently, alternative strategies that prevent intravaginal transmission of HIV (infection through the vagina) are urgently needed, particularly strategies that women can use without their partner's agreement. A vaccine would be ideal but it could be many years before an effective HIV vaccine is available so researchers are investigating other preventative strategies such as the use of microbicides—compounds that protect against HIV when applied inside the vagina—and pre-exposure treatment (prophylaxis) with antiretroviral drugs.
Why Was This Study Done?
Before any new strategy to prevent intravaginal HIV transmission is tried by women, it has to be tested in animals. Currently, this can only be done in macaques, an expensive option. In this study, the researchers have investigated whether “humanized BLT” mice could be used instead. When HIV enters the human body during vaginal intercourse, it sticks to dendritic cells (a type of immune system cell) in the vaginal lining. These cells carry the virus to the body's lymphoid tissues (collections of immune cells), where it infects and kills CD4+ T cells (another type of immune cell). Dendritic cells and CD4+ T cells have molecules on their surface that HIV recognizes. Mice are not normally susceptible to infection with HIV because their immune system cells lack these molecules. Humanized BLT mice have a nearly human immune system—BLT stands for bone marrow, liver, thymus. They are produced by implanting pieces of human fetal liver and thymus (the organ where T cells learn to recognize foreign invaders) under the kidney capsule of immunodeficient mice (animals born without an immune system) and then transplanting human hematopoietic stem cells (the source of the major immune system cells) into the mice.
What Did the Researchers Do and Find?
When the researchers examined the female reproductive tract of humanized BLT mice for human immune system cells, they found CD4+ T cells, dendritic cells and macrophages, all of which are involved in HIV infection. Furthermore, half of the blood cells of the BLT mice were human. Most of the BLT mice, the researchers report, were susceptible to intravaginal HIV infection as shown, for example, by a rapid loss of human CD4+ T cells from their blood. However, BLT mice pretreated with antiretroviral drugs (a mixture of emtricitabine and tenofovir disoproxil fumarate) were resistant to intravaginal HIV infection. As in human HIV infections, CD4+ T cells were also depleted in several other organs of the BLT mice after intravaginal HIV infection. Again, this depletion was prevented by antiretroviral pre-exposure prophylaxis. Finally, human CD4+ T cells also disappeared from the gut-associated lymphoid tissue (an important site for HIV replication and CD4+ T cell depletion during human HIV disease) of the BLT mice after infection with HIV.
What Do These Findings Mean?
These findings show that humanized BLT mice are susceptible to intravaginal infection with HIV and that many aspects of HIV infection in these mice closely mimic infection in people. In addition, by showing that pre-exposure prophylaxis with antiretroviral drugs prevents HIV infection, these results suggest that humanized BLT mice could be used to test new strategies designed to prevent intravaginal infection. As with all animal models, any approach that works in humanized BLT mice will still have to be tested in people. Nevertheless, these findings provide preclinical evidence that pre-exposure prophylaxis with antiretroviral drugs may be an effective way to prevent intravaginal transmission of HIV and, therefore, provide valuable support for clinical trials of this approach.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0050016.
Information is available from the US National Institute of Allergy and Infectious Diseases on HIV infection and AIDS and on HIV infection in women
HIVInSite has comprehensive information on all aspects of HIV/AIDS, including articles on women and HIV and on safer sex, which includes information on pre-exposure prophylaxis and microbicides
Information is available from Avert, an international AIDS charity, on HIV prevention, on women, HIV, and AIDS, and on microbicides
The US Centers for Disease Control and Prevention provides information on HIV/AIDS, including information on HIV/AIDS among women and on CDC trials of pre-exposure prophylaxis for HIV prevention (in English and some information in Spanish)
PrEP Watch is a comprehensive information source on pre-exposure prophylaxis for HIV prevention
doi:10.1371/journal.pmed.0050016
PMCID: PMC2194746  PMID: 18198941

Results 1-25 (1404611)