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1.  Optimal Uses of Antiretrovirals for Prevention in HIV-1 Serodiscordant Heterosexual Couples in South Africa: A Modelling Study 
PLoS Medicine  2011;8(11):e1001123.
Hallett et al use a mathematical model to examine the long-term impact and cost-effectiveness of different pre-exposure prophylaxis (PrEP) strategies for HIV prevention in serodiscordant couples.
Background
Antiretrovirals have substantial promise for HIV-1 prevention, either as antiretroviral treatment (ART) for HIV-1–infected persons to reduce infectiousness, or as pre-exposure prophylaxis (PrEP) for HIV-1–uninfected persons to reduce the possibility of infection with HIV-1. HIV-1 serodiscordant couples in long-term partnerships (one member is infected and the other is uninfected) are a priority for prevention interventions. Earlier ART and PrEP might both reduce HIV-1 transmission in this group, but the merits and synergies of these different approaches have not been analyzed.
Methods and Findings
We constructed a mathematical model to examine the impact and cost-effectiveness of different strategies, including earlier initiation of ART and/or PrEP, for HIV-1 prevention for serodiscordant couples. Although the cost of PrEP is high, the cost per infection averted is significantly offset by future savings in lifelong treatment, especially among couples with multiple partners, low condom use, and a high risk of transmission. In some situations, highly effective PrEP could be cost-saving overall. To keep couples alive and without a new infection, providing PrEP to the uninfected partner could be at least as cost-effective as initiating ART earlier in the infected partner, if the annual cost of PrEP is <40% of the annual cost of ART and PrEP is >70% effective.
Conclusions
Strategic use of PrEP and ART could substantially and cost-effectively reduce HIV-1 transmission in HIV-1 serodiscordant couples. New and forthcoming data on the efficacy of PrEP, the cost of delivery of ART and PrEP, and couples behaviours and preferences will be critical for optimizing the use of antiretrovirals for HIV-1 prevention.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Every year, about 2.5 million people become infected with HIV, the virus that causes AIDS. HIV is usually transmitted through unprotected sex with an HIV-infected partner. It destroys immune system cells (including CD4 cells, a type of lymphocyte), leaving infected individuals susceptible to other infections. There is no cure for AIDS, although HIV can be held in check with antiretroviral therapy (ART), and there is no vaccine that protects against HIV infection. So, to halt the AIDS epidemic, other ways of preventing the spread of HIV are needed. Antiretroviral drugs could potentially be used in two ways to reduce HIV transmission. First, ART could be given to HIV-infected people before they need it for their own health to reduce their infectiousness; the World Health Organization currently recommends that HIV-positive people initiate ART when their CD4 count drops below 350 cells/µl blood but in many African countries ART is only initiated when CD4 counts fall below 200 cells/µl. Second, ART could be given to HIV-uninfected people to reduce acquisition of the virus. This approach—preexposure prophylaxis (PrEP)—has provided protection against HIV transmission in some but not all clinical trials.
Why Was This Study Done?
Couples in long-term relationships where one partner is HIV-positive and the other is HIV-negative (HIV serodiscordant couples) are a priority group for prevention interventions. In sub-Saharan Africa, where most new HIV infections occur, 10%–20% of stable partnerships are serodiscordant and condom use is often low, not least because such couples may want children. Earlier ART or PrEP might reduce HIV transmission in this group but the merits of different approaches have not been analyzed. In this study, the researchers use a mathematical model to examine the long-term impact and cost-effectiveness of different PrEP and ART strategies for HIV prevention in serodiscordant couples.
What Did the Researchers Do and Find?
The researchers constructed a model to simulate HIV infection and disease progression among hypothetical HIV serodiscordant stable heterosexual couples. The model incorporated data from South Africa on couple characteristics, disease progression, ART use, pregnancies, frequency of sex, and contact with other sexual partners, as well as estimates of the effectiveness of PrEP from clinical trials. The researchers used the model to compare the impact on HIV transmission, survival and quality of life, and the cost-effectiveness of no PrEP with four PrEP strategies—always use PrEP after diagnosis of HIV serodiscordancy, use PrEP up to and for a year after ART initiation by the HIV-infected partner (at a CD4 count of ≤200 cells/µl or ≤350 cells/µl), use PrEP only up to ART initiation by the infected partner, and use PrEP only while trying for a baby and during pregnancy. The model predicts, for example, that the cost per infection averted of PrEP used before ART initiation will be offset by future savings in lifelong treatment, particularly among couples with multiple partners, low condom use, and a high risk of transmission. To keep couples alive without the HIV-uninfected partner becoming infected, it could be more cost-effective to provide PrEP to the uninfected partner than to initiate ART earlier in the infected partner, provided the annual cost of PrEP is less than 40% of the annual cost of ART and PrEP is more than 70% effective. Finally, if PREP is 30%–60% effective, the most cost-effective strategy for couples could be to use PrEP in the uninfected partner prior to ART initiation in the infected partner at a CD4 count ≤350 cells/µl.
What Do These Findings Mean?
These findings suggest that the strategic use of PrEP and ART could cost-effectively reduce HIV transmission in HIV serodiscordant stable heterosexual couples in sub-Saharan Africa. The accuracy of these findings depends on the assumptions included in the mathematical model and on the data fed into it. In particular, the interpretation of these results is complicated by uncertainties in the likely cost of PrEP and the “real-world” effectiveness of PrEP. Nevertheless, these findings suggest that PrEP may become a valuable addition in some settings to existing approaches for HIV prevention such as condom promotion and male circumcision programs. Moreover, additional simulations with this mathematical model using more accurate information on the costs and effectiveness of PrEP could assist in future policy making decisions.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001123.
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 a section on PrEP
Information is available from Avert, an international AIDS charity on many aspects of HIV/AIDS, including information on all aspects of HIV prevention, and on HIV/AIDS in Africa (in English and Spanish)
AVAC Global Advocacy for HIV Prevention provides up-to-date information on all aspects of HIV prevention, including PrEP
The US Centers for Disease Control and Prevention also has information on PrEP
WHO provides information about antiretroviral therapy
Patient stories about living with HIV/AIDS are available through Avert and through the charity website Healthtalkonline
doi:10.1371/journal.pmed.1001123
PMCID: PMC3217021  PMID: 22110407
2.  Adherence to Antiretroviral Prophylaxis for HIV Prevention: A Substudy Cohort within a Clinical Trial of Serodiscordant Couples in East Africa 
PLoS Medicine  2013;10(9):e1001511.
Jessica Haberer and colleagues investigate the association between high adherence to antiretroviral pre-exposure prophylaxis and HIV transmission in a substudy of serodiscordant couples participating in a clinical trial.
Please see later in the article for the Editors' Summary
Background
Randomized clinical trials of oral antiretroviral pre-exposure prophylaxis (PrEP) for HIV prevention have widely divergent efficacy estimates, ranging from 0% to 75%. These discrepancies are likely due to differences in adherence. To our knowledge, no studies to date have examined the impact of improving adherence through monitoring and/or intervention, which may increase PrEP efficacy, or reported on objective behavioral measures of adherence, which can inform PrEP effectiveness and implementation.
Methods and Findings
Within the Partners PrEP Study (a randomized placebo-controlled trial of oral tenofovir and emtricitabine/tenofovir among HIV-uninfected members of serodiscordant couples in Kenya and Uganda), we collected objective measures of PrEP adherence using unannounced home-based pill counts and electronic pill bottle monitoring. Participants received individual and couples-based adherence counseling at PrEP initiation and throughout the study; counseling was intensified if unannounced pill count adherence fell to <80%. Participants were followed monthly to provide study medication, adherence counseling, and HIV testing. A total of 1,147 HIV-uninfected participants were enrolled: 53% were male, median age was 34 years, and median partnership duration was 8.5 years. Fourteen HIV infections occurred among adherence study participants—all of whom were assigned to placebo (PrEP efficacy = 100%, 95% confidence interval 83.7%–100%, p<0.001). Median adherence was 99.1% (interquartile range [IQR] 96.9%–100%) by unannounced pill counts and 97.2% (90.6%–100%) by electronic monitoring over 807 person-years. Report of no sex or sex with another person besides the study partner, younger age, and heavy alcohol use were associated with <80% adherence; the first 6 months of PrEP use and polygamous marriage were associated with >80% adherence. Study limitations include potential shortcomings of the adherence measures and use of a convenience sample within the substudy cohort.
Conclusions
The high PrEP adherence achieved in the setting of active adherence monitoring and counseling support was associated with a high degree of protection from HIV acquisition by the HIV-uninfected partner in heterosexual serodiscordant couples. Low PrEP adherence was associated with sexual behavior, alcohol use, younger age, and length of PrEP use.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Every year, about 2.5 million people (mostly living in sub-Saharan Africa) become infected with HIV, the virus that causes AIDS. HIV, which is usually transmitted through unprotected sex with an HIV-infected partner, destroys immune system cells, leaving infected individuals susceptible to other infections. There is no cure for AIDS, although antiretroviral drugs can hold HIV in check, and there is no vaccine against HIV infection. Individuals can reduce their risk of HIV infection by abstaining from sex, by having only one or a few low risk sexual partners, and by always using a condom. In addition, antiretroviral drugs can potentially be used in two ways to reduce HIV transmission. First, these drugs could be given to HIV-positive individuals to reduce their infectiousness. Second, antiretroviral drugs could be given to HIV-uninfected people to reduce acquisition of the virus. This approach—pre-exposure prophylaxis (PrEP)—has provided varying levels of protection against HIV infection in randomized controlled trials (RCT; studies that monitor the outcomes of groups of patients randomly assigned to receive different test drugs or a placebo/dummy drug).
Why Was This Study Done?
One hypothesis for the varying efficacy of PrEP in RCTs is differential adherence—differences in whether trial participants took the antiretroviral drugs correctly. Antiretroviral drugs only control HIV infections effectively when they are taken regularly and adherence to antiretroviral PrEP is probably also important for HIV prevention. Here, the researchers investigate adherence to antiretroviral prophylaxis in a substudy within the Partners PrEP Study, a placebo-controlled RCT of oral antiretroviral drugs among nearly 5,000 HIV-uninfected members of serodiscordant couples in East Africa. In serodiscordant couples, only one partner is HIV-positive; 20% of couples in Africa who know their HIV status are serodiscordant. In the Partner PrEP Study, the efficacy of HIV protection with oral antiretroviral drugs was 67%–75%.
What Did the Researchers Do and Find?
The researchers selected a “convenience” sample—a sample is taken non-randomly from a population that is close at hand—of 1,147 HIV-uninfected partners enrolled in Uganda. They used unannounced home-based pill counts (an approach that reduced the chance of participants dumping unused pills to appear more adherent than they actually were) and electronic pill bottle monitoring (a microchip in the medication bottle cap recorded whenever the bottle was opened) to measure PrEP adherence in this cohort. All the participants received adherence counseling at PrEP initiation and throughout the study; counseling was intensified if unannounced pill count adherence fell below 80%. Fourteen participants, all of whom had been assigned to placebo, became HIV-positive during the adherence substudy. The average adherence to PrEP was 99.1% and 97.2% as measured by unannounced pill counts and by electronic monitoring, respectively. About 7% and 26% of participants had less than 80% adherence as measured by unannounced pill count and electronic monitoring, respectively, during at least one 3-month period of the substudy. Greater than 80% adherence was associated with the first 6 months of PrEP use and polygamous marriage. Adherence less than 80% was associated with report of no sex or sex with another person besides the study partner, younger age, and heavy alcohol use. Finally, the adherence intervention (intensified counseling) was well received and in the first unannounced pill count after the intervention, adherence increased to above 80% in 92% of participants.
What Do These Findings Mean?
These findings indicate that the high level of PrEP adherence achieved in the setting of active adherence monitoring and counseling support was associated with a high level of protection from HIV acquisition by the HIV-uninfected partner in heterosexual serodiscordant couples. The findings also suggest that low PrEP adherence is associated with sexual behavior, alcohol use, younger age, and length of PrEP use. Several aspects of the study design may limit the accuracy of these findings. For example, although the adherence measures used here are probably more accurate than participant reports of missed doses and clinic-based pill counts (adherence measures that are often used in RCTs), they are not perfect. Nevertheless, these findings provide further support for the ability of PrEP to prevent HIV acquisition when taken regularly; they suggest that adherence interventions in the implementation setting should address sexual behavior, risk perception, and heavy alcohol use; and they provide data to guide ethical decisions about resource allocation for prevention and treatment of HIV infection.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001511.
The 2012 UNAIDS World AIDS Day Report provides up-to-date information about the AIDS epidemic and efforts to halt it
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 HIV transmission and prevention and on PrEP
Information is available from Avert, an international AIDS charity, on many aspects of HIV/AIDS, including information on HIV and AIDS in Uganda, on HIV prevention, and on PrEP (in English and Spanish)
PrEP Watch provides detailed information about PrEP and links to other resources; it includes personal stories from people who have chosen to use PrEP
More information about the Partners PrEP Study is available
Personal stories about living with HIV/AIDS are available through Avert, through Nam/aidsmap, and through the charity website Healthtalkonline
doi:10.1371/journal.pmed.1001511
PMCID: PMC3769210  PMID: 24058300
3.  Antiretrovirals and safer conception for HIV-serodiscordant couples 
Current opinion in HIV and AIDS  2012;7(6):569-578.
Purpose of review
Many men and women living with HIV and their uninfected partners attempt to conceive children. HIV-prevention science can be applied to reduce sexual transmission risk while respecting couples’ reproductive goals. Here we discuss antiretrovirals as prevention in the context of safer conception for HIV-serodiscordant couples.
Recent findings
Antiretroviral therapy (ART) for the infected partner and pre-exposure prophylaxis (PrEP) for the uninfected partner reduce the risk of heterosexual HIV transmission. Several demonstration projects suggest the feasibility and acceptability of antiretroviral (ARV)s as periconception HIV-prevention for HIV-serodiscordant couples. The application of ARVs to periconception risk reduction may be limited by adherence.
Summary
For male-infected (M+F−) couples who cannot access sperm processing and female-infected (F+M−) couples unwilling to carry out insemination without intercourse, ART for the infected partner, PrEP for the uninfected partner, combined with treatment for sexually transmitted infections, sex limited to peak fertility, and medical male circumcision (for F+M couples) provide excellent, well tolerated options for reducing the risk of periconception HIV sexual transmission.
doi:10.1097/COH.0b013e328358bac9
PMCID: PMC3695736  PMID: 23032734
antiretrovirals as prevention; conception; fertility; HIV prevention; HIV-serodiscordance; perinatal HIV transmission; sexual HIV transmission
4.  Reproductive health options among HIV-infected persons in the low-income Niger Delta of Nigeria 
Background
With the advent and widespread use of highly active antiretroviral therapy for the treatment of human immunodeficiency virus (HIV), persons living with HIV/acquired immune deficiency syndrome (AIDS) are living good quality, longer, and healthier lives. Many couples affected by HIV, both serodiscordant and seroconcordant, are beginning to consider options for safer reproduction. The aim of this study was to assess the reproductive health concerns among persons living with HIV/AIDS in the Niger Delta of Nigeria.
Methods and results
The subjects were aged 18–58 (mean 41.25 ± 11.50) years, with 88 males (45.1%) and 107 females (54.9). Of the 195 subjects studied, 111 (56.9%) indicated a desire to have children. The main reasons for wanting to procreate included ensuring lineage continuity and posterity (52.3%), securing relationships (27.0%), and pressure from relatives to reproduce (20.7%). Single subjects were more inclined to have children (76.3%) compared with married (51.5%), widowed (18.2%), and separated/divorced subjects (11.1%, P = 0.03). Of the 111 subjects who indicated their desire to have children, women were more inclined to have children (64.5%) than men (47.7%). The major concern among the 84 (43.1%) subjects not desiring more children were the fear of infecting a serodiscordant partner and baby (57.1%), fear of dying and leaving behind orphans (28.6%), and fear that they may become too ill and unable to support the child financially (14.3%). Persons with no formal education were more likely to have children irrespective of their positive HIV status (66.7%) than persons educated to tertiary education level (37.0%, P = 0.01). Of 111 subjects who desired to have children, only 58% had attended reproductive health counseling with HIV counselors. Reasons for not seeking advice were anticipated negative reactions and discrimination from counselors. A significant number of subjects were only aware of some of the reproductive health options available to reduce the risk of infecting their partners and/or baby, such as artificial vaginal insemination, intrauterine insemination, cesarean section, avoidance of breast feeding, and offering prenatal pre-exposure prophylaxis to the fetus. They were unaware of other options, such as sperm washing, in vitro fertilization, and intracytoplasmic sperm injection. Of the 43.1% not anticipating more children, 36.9% were anticipating adoption.
Conclusion
Our study has shown that a significant number of HIV-infected persons in the Niger Delta of Nigeria desire to have children irrespective of their positive serostatus. There is the need to support the sexual and reproductive rights of HIV-infected individuals. Additional training needs to be offered to HIV counselors on evidence-based best and affordable practices regarding reproductive health issues among persons living with HIV. Policies that support availability and accessibility to relevant reproductive and sexual health services, including contraception and procreation, need to be developed. Public enlightenment programs on HIV are needed to reduce the stigmatization that HIV-infected persons face from family members and their communities.
doi:10.2147/HIV.S19413
PMCID: PMC3284261  PMID: 22359465
reproductive health; human immunodeficiency virus; low income; Niger Delta; Nigeria
5.  Systematic Review of Abstinence-Plus HIV Prevention Programs in High-Income Countries 
PLoS Medicine  2007;4(9):e275.
Background
Abstinence-plus (comprehensive) interventions promote sexual abstinence as the best means of preventing HIV, but also encourage condom use and other safer-sex practices. Some critics of abstinence-plus programs have suggested that promoting safer sex along with abstinence may undermine abstinence messages or confuse program participants; conversely, others have suggested that promoting abstinence might undermine safer-sex messages. We conducted a systematic review to investigate the effectiveness of abstinence-plus interventions for HIV prevention among any participants in high-income countries as defined by the World Bank.
Methods and Findings
Cochrane Collaboration systematic review methods were used. We included randomized and quasi-randomized controlled trials of abstinence-plus programs for HIV prevention among any participants in any high-income country; trials were included if they reported behavioural or biological outcomes. We searched 30 electronic databases without linguistic or geographical restrictions to February 2007, in addition to contacting experts, hand-searching conference abstracts, and cross-referencing papers. After screening 20,070 abstracts and 325 full published and unpublished papers, we included 39 trials that included approximately 37,724 North American youth. Programs were based in schools (10), community facilities (24), both schools and community facilities (2), health care facilities (2), and family homes (1). Control groups varied. All outcomes were self-reported. Quantitative synthesis was not possible because of heterogeneity across trials in programs and evaluation designs. Results suggested that many abstinence-plus programs can reduce HIV risk as indicated by self-reported sexual behaviours. Of 39 trials, 23 found a protective program effect on at least one sexual behaviour, including abstinence, condom use, and unprotected sex (baseline n = 19,819). No trial found adverse program effects on any behavioural outcome, including incidence of sex, frequency of sex, sexual initiation, or condom use. This suggests that abstinence-plus approaches do not undermine program messages encouraging abstinence, nor do they undermine program messages encouraging safer sex. Findings consistently favoured abstinence-plus programs over controls for HIV knowledge outcomes, suggesting that abstinence-plus programs do not confuse participants. Results for biological outcomes were limited by floor effects. Three trials assessed self-reported diagnosis or treatment of sexually transmitted infection; none found significant effects. Limited evidence from seven evaluations suggested that some abstinence-plus programs can reduce pregnancy incidence. No trial observed an adverse biological program effect.
Conclusions
Many abstinence-plus programs appear to reduce short-term and long-term HIV risk behaviour among youth in high-income countries. Programs did not cause harm. Although generalisability may be somewhat limited to North American adolescents, these findings have critical implications for abstinence-based HIV prevention policies. Suggestions are provided for improving the conduct and reporting of trials of abstinence-plus and other behavioural interventions to prevent HIV.
In their systematic review, Underhill and colleagues found that abstinence-plus programs appear to reduce short-term and long-term HIV risk behavior among youth in high-income countries.
Editors' Summary
Background.
Human immunodeficiency virus (HIV), which causes AIDS, is most often spread through unprotected sex (vaginal, oral, or anal) with an infected partner. Individuals can reduce their risk of becoming infected with HIV by abstaining from sex or delaying first sex, by being faithful to one partner or having few partners, and by always using a male or female condom. Various HIV prevention programs targeted at young people encourage these protective sexual behaviors. Abstinence-only programs (for example, Project Reality in the US) present no sex before marriage as the only means of reducing the risk of catching HIV. Abstinence-plus programs (for example, the UK Apause program) also promote sexual abstinence as the safest behavior choice to prevent HIV infection. However, recognizing that not everyone will remain abstinent, and that in many locations same-sex couples are not permitted to marry, abstinence-plus programs also encourage young people who do become sexually active to use condoms and other safer-sex strategies. Safer-sex programs, a third approach, teach people how to protect themselves from pregnancy and infections and might recommend delaying first sex until they are physically and emotionally ready, but do not promote sexual abstinence over safer-sex strategies such as condom use.
Why Was This Study Done?
There is considerable controversy, particularly in the US, about the relative merits of abstinence-based programs for HIV prevention. Abstinence-only programs, which the US government supports, have been criticized because they provide no information to protect participants who do become sexually active. Critics of abstinence-plus programs contend that teaching young people about safer sex undermines the abstinence message, confuses participants, and may encourage them to become sexually active. Conversely, some people worry that the promotion of abstinence might undermine the safer-sex messages of abstinence-plus programs. Little has been done, however, to look methodically at how these programs change sexual behavior. In this study, the researchers have systematically reviewed studies of abstinence-plus interventions for HIV prevention in high-income countries to get an idea of their effect on sexual behavior.
What Did the Researchers Do and Find?
In an extensive search for existing abstinence-plus studies, the researchers identified 39 trials done in high-income countries that compared the effects on sexual behavior of various abstinence-plus programs with the effects of no intervention or of other interventions designed to prevent HIV infection. All the trials met strict preset criteria (for example, trial participants had to have an unknown or negative HIV status), and all studies meeting the criteria turned out to involve young people in the US, Canada, or the Bahamas, nearly 40,000 participants in total. In 23 of the trials, the abstinence-plus program studied was found to improve at least one self-reported protective sexual behavior (for example, it increased abstinence or condom use) when compared to the other interventions in the trial; none of the trials reported a significant negative effect on any behavioral outcome. Limited evidence from a few trials indicated that some abstinence-plus programs reduced pregnancy rates, providing a biological indicator of program effectiveness. Conversely, there were no indications of adverse biological outcomes such as an increased occurrence of sexually transmitted diseases in any of the trials.
What Do These Findings Mean?
These findings indicate that some abstinence-plus programs reduce HIV risk behavior among young people in North America. Importantly, the findings do not uncover evidence of any abstinence-plus program causing harm. That is, fears that these programs might encourage young people to become sexually active earlier or confuse them about the use of condoms for HIV prevention seem unfounded. These findings may not apply to all abstinence-plus programs in high-income countries, do not include low-income countries, do not specifically address nonheterosexual risk behavior, and are subject to limited reliability in self-reporting of sexual activity by young people. Nonetheless, this analysis provides support for the use of abstinence-plus programs, particularly in light of another systematic review by the same authors (A systematic review of abstinence-only programs for prevention of HIV infection, published in the British Medical Journal), which found that abstinence-only programs did not reduce pregnancy, sexually transmitted diseases, or sexual behaviors that increase HIV risk. Abstinence-plus programs, these findings suggest, represent a reasonable strategy for HIV prevention among young people in high-income countries.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0040275.
• US National Institute of Allergy and Infectious Diseases fact sheet on HIV infection and AIDS
• Information from the UK charity AVERT on all aspects of HIV and AIDS, including HIV and AIDS prevention
• US Centers for Disease Control and Prevention fact sheet on HIV/AIDS among young people (in English and Spanish)
• Information on Project Reality, a US abstinence-only program
• Information on Reducing the Risk and on Apause, US and UK abstinence-plus programs, respectively
doi:10.1371/journal.pmed.0040275
PMCID: PMC1976624  PMID: 17880259
6.  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
7.  The Opposites Attract Study of viral load, HIV treatment and HIV transmission in serodiscordant homosexual male couples: design and methods 
BMC Public Health  2014;14(1):917.
Background
Studies in heterosexual HIV serodiscordant couples have provided critical evidence on the role of HIV treatments and undetectable viral load in reducing the risk of HIV transmission. There is very limited data on the risk of transmission from anal sex in homosexual male serodiscordant couples.
Methods/Design
The Opposites Attract Study is an observational prospective longitudinal cohort study of male homosexual serodiscordant partnerships running from 2012 to 2015 and conducted in clinics throughout Australia, Brazil and Thailand. Couples attend two or more clinic visits per year. The HIV-positive partner’s viral load is tested and the HIV-negative partner is tested for HIV antibodies at every clinic visit. Results from any tests for sexually transmitted infections are also collected. Detailed behavioural questionnaires are completed by both partners at the time of each visit. The primary research question is whether HIV incidence is lower in those couples where the HIV-positive partner is receiving HIV treatment compared to couples where he is not receiving treatment. A voluntary semen sub-study will examine semen plasma viral load in a subsample of HIV-positive partners in Sydney, Rio de Janeiro and Bangkok. In cases of seroconversion of the initially HIV-negative partner, phylogenetic analysis will be conducted at the end of the study on virus from stored blood samples from both partners to determine if the infection came from the HIV-positive study partner. Men in new serodiscordant relationships will specifically be targeted for recruitment.
Discussion
This study will provide critical data on the reduction in HIV transmission risk associated with being on HIV treatment in homosexual male serodiscordant couples in different regions of the world. Data from men in new relationships will be particularly valuable given that the highest transmission risk is in the first year of serodiscordant relationships. Furthermore, the detailed behavioural and attitudinal data from the participant questionnaires will allow exploration of many contextual factors associated with HIV risk, condom use and the negotiation of sexual practice within couples.
doi:10.1186/1471-2458-14-917
PMCID: PMC4168197  PMID: 25190360
HIV treatment as prevention; Serodiscordant; Homosexual; HIV transmission; Antiretroviral therapy
8.  A Qualitative Study of Barriers to Consistent Condom Use among HIV-1 Serodiscordant Couples in Kenya 
AIDS care  2011;24(4):509-516.
This study explored barriers to consistent condom use among heterosexual HIV-1 serodiscordant couples who were aware of the HIV-1 serodiscordant status and had been informed about condom use as a risk reduction strategy. We conducted 28 in-depth interviews and 9 focus group discussions among purposively-selected heterosexual HIV-1 serodiscordant couples from Thika and Nairobi districts in Kenya. We analyzed the transcribed data with a grounded theory approach. The most common barriers to consistent condom use included male partners’ reluctance to use condoms regardless of HIV-1 status coupled with female partners’ inability to negotiate condom use, misconceptions about HIV-1 serodiscordance, and desire for children. Specific areas of focus should include development of skills for women to effectively negotiate condom use, ongoing information on HIV-1 serodiscordance and education on safer conception practices that minimize risk of HIV-1 transmission.
doi:10.1080/09540121.2011.613911
PMCID: PMC3932299  PMID: 22085306
HIV-1; Serodiscordant; Condom use; Kenya
9.  South Africans with recent pregnancy rarely know partner’s HIV serostatus: implications for serodiscordant couples interventions 
BMC Public Health  2014;14(1):843.
Background
Implementation of safer conception strategies requires knowledge of partner HIV-serostatus. We recruited women and men in a high HIV-prevalence setting for a study to assess periconception risk behavior among individuals reporting HIV-serodiscordant partnerships. We report screening data from that study with the objective of estimating the proportion of individuals who are aware that they are in an HIV-serodiscordant relationship at the time of conception.
Methods
We screened women and men attending antenatal and antiretroviral clinics in Durban, South Africa for enrollment in a study of periconception risk behavior among individuals with serodiscordant partners. Screening questionnaires assessed for study eligibility including age 18–45 years (for women) or at least 18 years of age (for men), pregnancy in past year (women) or partner pregnancy in the past 3 years (men), HIV status of partner for recent pregnancy, participant’s HIV status, and infected partner’s HIV status having been known before the referent pregnancy.
Results
Among 2620 women screened, 2344 (90%) met age and pregnancy criteria and knew who fathered the referent pregnancy. Among those women, 963 (41%) did not know the pregnancy partner’s HIV serostatus at time of screening. Only 92 (4%) reported knowing of a serodiscordant partnership prior to pregnancy. Among 1166 men screened, 225 (19%) met age and pregnancy criteria. Among those men, 71 (32%) did not know the pregnancy partner’s HIV status and only 30 (13%) reported knowing of a serodiscordant partnership prior to pregnancy.
Conclusions
In an HIV-endemic setting, awareness of partner HIV serostatus is rare. Innovative strategies to increase HIV testing and disclosure are required to facilitate HIV prevention interventions for serodiscordant couples.
doi:10.1186/1471-2458-14-843
PMCID: PMC4246447  PMID: 25124267
HIV prevention; HIV serodiscordant couples; Safer conception; HIV serostatus disclosure
10.  Association of Human Mannose Receptor in Sexual Transmission of Human Immunodeficiency Virus in Serodiscordant Couples 
Abstract
HIV binds specifically to the human mannose receptor (hMR) on vaginal epithelial cells that are devoid of a conventional CD4 receptor. HIV binding to hMR on vaginal epithelial cells induces the production of matrix metalloproteinase 9 (MMP9) leading to degradation of the extracellular matrix, which may increase the risk of HIV entry into vaginal epithelial cells and further transmission into distal cells. Immunofluorescent localization of hMR on vaginal epithelial cells of seronegative females from the general population included the control group (n=52) and seronegative females from serodiscordant couples. There was PCR amplification of DNA from peripheral blood mononuclear cells (PBMCs) of the serodiscordant females for the CCR5 gene flanking the CCR5-Δ32 region; PCR amplification and sequencing of the C2-V3 region of HIV variants in PBMCs and sperm of the infected male partners of the serodiscordant couples; and the presence of hMR on 0–11% of the vaginal epithelial cells of seronegative females (n=39) from serodiscordant couples and 90–95% that of a control group of females (n=52). Nine of these serodiscordant females did not show a CCR5-Δ32 deletion. The translated amino acid sequence of the C2-V3 region of the env gene of HIV-1C in PBMCs (n=9) and sperm (n=5) of the male partners showed the presence of distinct variants and the variation in PBMCs and sperm of serodiscordant males was almost similar to that of infected males from concordant couples. The presence of hMR in a smaller number of vaginal epithelial cells of serodiscordant females prevented binding and HIV entry into these cells and therefore prevented sexual transmission of HIV.
doi:10.1089/aid.2012.0101
PMCID: PMC3537322  PMID: 23148569
11.  Fathers and HIV: considerations for families 
Background
Fathers are intricately bound up in all aspects of family life. This review examines fathers in the presence of HIV: from desire for a child, through conception issues, to a summary of the knowledge base on fathers within families affected by HIV.
Methods
A mixed-methods approach is used, given the scarcity of literature. A review is provided on paternal and male factors in relation to the desire for a child, HIV testing in pregnancy, fatherhood and conception, fatherhood and drug use, paternal support and disengagement, fatherhood and men who have sex with men (MSM), and paternal effects on child development in the presence of HIV. Literature-based reviews and systematic review techniques are used to access available data Primary data are reported on the issue of parenting for men who have sex with men.
Results
Men with HIV desire fatherhood. This is established in studies from numerous countries, although fatherhood desires may be lower for HIV-positive men than HIV-negative men. Couples do not always agree, and in some studies, male desires for a child are greater than those of their female partners. Despite reduced fertility, support and services, many proceed to parenting, whether in seroconcordant or serodiscordant relationships. There is growing knowledge about fertility options to reduce transmission risk to uninfected partners and to offspring.
Within the HIV field, there is limited research on fathering and fatherhood desires in a number of difficult-to-reach groups. There are, however, specific considerations for men who have sex with men and those affected by drug use. Conception in the presence of HIV needs to be managed and informed to reduce the risk of infection to partners and children. Further, paternal support plays a role in maternal management.
Conclusions
Strategies to improve HIV testing of fathers are needed. Paternal death has a negative impact on child development and paternal survival is protective. It is important to understand fathers and fathering and to approach childbirth from a family perspective.
doi:10.1186/1758-2652-13-S2-S4
PMCID: PMC2890973  PMID: 20573286
12.  A Prospective Study of Frequency and Correlates of Intimate Partner Violence among African Heterosexual HIV Serodiscordant Couples 
AIDS (London, England)  2011;25(16):2009-2018.
Background
Intimate partner violence (IPV) is common worldwide and is an important consideration in couples HIV voluntary counseling and testing (CVCT), especially for HIV serodiscordant couples (i.e., in which only one member is HIV infected).
Design
Prospective study of 3408 HIV serodiscordant couples (2299 in which the HIV infected partner was female) from 7 countries from East and Southern Africa.
Methods
At quarterly visits during up to 2 years of follow-up, participants were asked, separately, about IPV perpetrated against them by their partner during the prior 3 months. Correlates of IPV were determined by generalized estimating equations.
Results
The majority of couples were married and living together, with an average duration of partnership of approximately 5 years. More than 39,000 quarterly visits were recorded. IPV was reported in 2.7% of visits by HIV infected women, 2.2% by HIV uninfected women, 0.9% by HIV infected men, and 0.7% by HIV uninfected men. The majority of IPV reports were verbal or a combination of verbal and physical violence. Those who were HIV infected were more likely to report IPV (for women adjusted odds ratio [AOR] 1.33, p=0.043; for men AOR 2.20, p=0.001), but IPV was not significantly associated with risk of HIV seroconversion in HIV uninfected participants. IPV incidence decreased during follow-up (p<0.001).
Conclusions
During up to 2 years of prospective follow-up, most persons in stable HIV serodiscordant partnerships who had undergone CVCT did not report IPV. A modest increased risk of IPV was seen for HIV infected partners, both female and male.
doi:10.1097/QAD.0b013e32834b005d
PMCID: PMC3718250  PMID: 21811146
intimate partner violence; HIV serodiscordant couples; women; Africa
13.  HIV-1 Prevention for HIV-1 Serodiscordant Couples 
Current HIV/AIDS reports  2012;9(2):160-170.
A substantial proportion of HIV-1-infected individuals in sub-Saharan Africa are in stable relationships with HIV-1-uninfected partners, and HIV-1 serodiscordant couples thus represent an important target population for HIV-1 prevention. Couple-based HIV-1 testing and counseling facilitates identification of HIV-1 serodiscordant couples, counseling about risk reduction, and referrals to HIV-1 treatment, reproductive health services, and support services. Maximizing HIV-1 prevention for HIV-1 serodiscordant couples requires a combination of strategies, including counseling about condoms, sexual risk, fertility, contraception, and the clinical and prevention benefits of antiretroviral therapy (ART) for the HIV-1-infected partner; provision of clinical care and ART for the HIV-1-infected partner; antenatal care and services to prevent mother to child transmission for HIV-1- infected pregnant women; male circumcision for HIV-1-uninfected men; and, pending guidelines and demonstration projects, oral pre-exposure prophylaxis (PrEP) for HIV-1-uninfected partners.
doi:10.1007/s11904-012-0114-z
PMCID: PMC3570050  PMID: 22415473
HIV-1 serodiscordant couples; HIV-1 prevention; Africa; antiretroviral; ART; PrEP
14.  Provider Attitudes toward Discussing Fertility Intentions with HIV-Infected Women and Serodiscordant Couples in the USA 
Background
Recent research suggests that pregnancy is a potentially safe option for couples with at least one HIV-infected adult. Data regarding provider discussion of fertility intentions with women living with HIV (WLWH) or in serodiscordant relationships is limited.
Methods
We conducted a cross-sectional self-administered survey of health professionals who provide HIV services to women in order to assess knowledge and behaviors regarding family planning options for HIV-infected women and serodiscordant couples.
Results
Of 77 respondents, 47(61%) met the inclusion criteria (health care provider who cares for WLWH). Approximately half (57%) of the participants indicated that they always or usually discuss contraception or fertility intentions with their HIV+ female patients of reproductive age. When asked to indicate their awareness of techniques to decrease HIV transmission risk among serodiscordant couples attempting pregnancy, most participants reported awareness of multiple options. Discussion of contraception or fertility intentions was not associated with provider gender, age, and experience in caring for HIV-infected patients, previous training in women’s health or provider’s awareness of options to decrease transmission risk.
Conclusions
HIV providers in this study were knowledgeable of practices that can lead to safer conception and prevent HIV transmission among individuals in serodiscordant relationships but did not always discuss this information with their patients. Further research is needed to explore optimal methods for encouraging such conversations.
doi:10.4172/2155-6113.1000307
PMCID: PMC4160891  PMID: 25221730
HIV; Provider; Fertility; Serodiscordant couples; Women
15.  Determinants of Per-Coital-Act HIV-1 Infectivity Among African HIV-1–Serodiscordant Couples 
The Journal of Infectious Diseases  2012;205(3):358-365.
(See the editorial commentary by Gray and Wawer on pages 351–2.)
Background. Knowledge of factors that affect per-act infectivity of human immunodeficiency virus type 1 (HIV-1) is important for designing HIV-1 prevention interventions and for the mathematical modeling of the spread of HIV-1.
Methods. We analyzed data from a prospective study of African HIV-1–serodiscordant couples. We assessed transmissions for linkage within the study partnership, based on HIV-1 sequencing. The primary exposure measure was the HIV-1–seropositive partners’ reports of number of sex acts and condom use with their study partner.
Results. Of 3297 couples experiencing 86 linked HIV-1 transmissions, the unadjusted per-act risks of unprotected male-to-female (MTF) and female-to-male (FTM) transmission were 0.0019 (95% confidence interval [CI], .0010–.0037) and 0.0010 (95% CI, .00060–.0017), respectively. After adjusting for plasma HIV-1 RNA of the HIV-1–infected partner and herpes simplex virus type 2 serostatus and age of the HIV-1–uninfected partner, we calculated the relative risk (RR) for MTF versus FTM transmission to be 1.03 (P = .93). Each log10 increase in plasma HIV-1 RNA increased the per-act risk of transmission by 2.9-fold (95% CI, 2.2–3.8). Self-reported condom use reduced the per-act risk by 78% (RR = 0.22 [95% CI, .11–.42]).
Conclusions. Modifiable risk factors for HIV-1 transmission were plasma HIV-1 RNA level and condom use, and, in HIV-1–uninfected partners, herpes simplex virus 2 infection, genital ulcers, Trichomonas vaginalis, vaginitis or cervicitis, and male circumcision.
doi:10.1093/infdis/jir747
PMCID: PMC3256946  PMID: 22241800
16.  Profile of HIV seroconcordant/discordant couples a clinic based study at Vadodara, India 
Background:
Heterosexual transmission of HIV among married couples is the commonest mode of transmission seen in India. Intramarital transmission is associated with several challenges which need to be further researched.
Aim:
To study level of seroconcordance and serodiscordance among HIV positive couples and factors affecting intramarital sexual transmission in terms of safe sexual practice, and the presence of Sexually transmitted infections (STI)/circumcision.
Materials and Methods:
Ninety-one monogamous married cohabiting HIV-positive cases (index cases) attending Department of Skin and Venereology, Medical College Baroda, from January 2009 to August 2009 were studied. Their spouses were tested for HIV. A structured proforma was used to study various factors like condom use, circumcision, and the presence of sexually transmitted infections.
Results:
Ninety-one monogamous married cohabiting HIV-positive cases were included in the study and considered as index cases. There were 51 males and 40 females. On testing their spouses for HIV, both the spouses were positive in 55 couples giving rise to 60% seroconcordance rate. Out of 55 seroconcordant couples, male spouses used condom in 16 cases (29%). Out of 36 serodiscordant couples 17 male spouses (47%) used condom. Evidence of STD was observed in one of the spouses in 6 out of 55 seroconcordant couples and 6 out of 36 serodiscordant couples. Thus, out of 91 couples one of the partners was having STI in 12 couples. Overall rate of circumcision was 12.2%.
Conclusion:
The prevention of transmission of HIV to the HIV negative partner is of paramount importance. Serodiscordant couples, specially the HIV negative female partner is at higher risk. Less acceptability of condoms among married couples may be one of the factors responsible in transmission. Further studies are needed to explore other risk factors associated with HIV transmission in discordant couples.
doi:10.4103/0253-7184.112862
PMCID: PMC3730477  PMID: 23919047
Circumcision; condom; HIV/AIDS; seroconcordant-discordant; STD
17.  Challenges with couples, serodiscordance and HIV disclosure: healthcare provider perspectives on delivering safer conception services for HIV-affected couples, South Africa 
Introduction
Introduction Safer conception interventions should ideally involve both members of an HIV-affected couple. With serodiscordant couples, healthcare providers will need to manage periconception risk behaviour as well tailor safer conception strategies according to available resources and the HIV status of each partner. Prior to widespread implementation of safer conception services, it is crucial to better understand provider perspectives regarding provision of care since they will be pivotal to the successful delivery of safer conception. This paper reports on findings from a qualitative study exploring the viewpoints and experiences of doctors, nurses, and lay counsellors on safer conception care in a rural and in an urban setting in Durban, South Africa.
Methods
We conducted six semistructured individual interviews per site (a total of 12 interviews) as well as a focus group discussion at each clinic site (a total of 13 additional participants). All interviews were coded in Atlas.ti using a grounded theory approach to develop codes and to identify core themes and subthemes in the data.
Results
Managing the clinical and relationship complexities related to serodiscordant couples wishing to conceive was flagged as a concern by all categories of health providers. Providers added that, in the HIV clinical setting, they often found it difficult to balance their professional priorities, to maintain the health of their clients, and to ensure that partners were not exposed to unnecessary risk, while still supporting their clients’ desires to have a child. Many providers expressed concern over issues related to disclosure of HIV status between partners, particularly when managing couples where one partner was not aware of the other's status and expressed the desire for a child. Provider experiences were that female clients most often sought out care, and it was difficult to reach the male partner to include him in the consultation.
Conclusions
Providers require support in dealing with HIV disclosure issues and in becoming more confident in dealing with couples and serodiscordance. Prior to implementing safer conception programmes, focused training is needed for healthcare professionals to address some of the ethical and relationship issues that are critical in the context of safer conception care.
doi:10.7448/IAS.17.1.18832
PMCID: PMC3956311  PMID: 24629843
safer conception; couples; serodiscordance; healthcare providers
18.  High Medication Adherence During Periconception Periods Among HIV-1–Uninfected Women Participating in a Clinical Trial of Antiretroviral Pre-exposure Prophylaxis 
Introduction:
Pre-exposure prophylaxis (PrEP) may be an important safer conception strategy for HIV-1–uninfected women with HIV-1–infected partners. Understanding medication adherence in this population may inform whether PrEP is a feasible safer conception strategy.
Methods:
We evaluated predictors of pregnancy and adherence to study medication among HIV-1–uninfected women enrolled in a randomized placebo-controlled trial of PrEP among African HIV-1–serodiscordant couples. Participants were counseled on HIV-1 risk reduction, contraception, and adherence and tested for pregnancy at monthly study visits. Pill counts of dispensed drug were performed and, at a subset of visits, plasma was collected to measure active drug concentration.
Results:
Among 1785 women, pregnancy incidence was 10.2 per 100 person-years. Younger age, not using contraception, having an additional sexual partner, and reporting unprotected sex were associated with increased likelihood of pregnancy. Monthly clinic pill counts estimated that women experiencing pregnancy took 97% of prescribed doses overall, with at least 80% pill adherence for 98% of study months, and no difference in adherence in the periconception period compared with previous periods (P = 0.98). Tenofovir was detected in plasma at 71% of visits where pregnancy was discovered. By multiple measures, adherence was similar for women experiencing and not experiencing pregnancy (P ≥ 0.1).
Conclusions:
In this clinical trial of PrEP, pregnancy incidence was 10% per year despite excellent access to effective contraception. Women experiencing pregnancy had high medication adherence, suggesting that PrEP may be an acceptable and feasible safer conception strategy for HIV-1–uninfected women with HIV-1–serodiscordant partners.
doi:10.1097/QAI.0000000000000246
PMCID: PMC4149628  PMID: 25118795
pregnancy; HIV-1 prevention; pre-exposure prophylaxis; adherence; safer conception; serodiscordant couples; sub-Saharan Africa
19.  HIV Status Awareness, Partnership Dissolution and HIV Transmission in Generalized Epidemics 
PLoS ONE  2012;7(12):e50669.
Objectives
HIV status aware couples with at least one HIV positive partner are characterized by high separation and divorce rates. This phenomenon is often described as a corollary of couples HIV Testing and Counseling (HTC) that ought to be minimized. In this contribution, we demonstrate the implications of partnership dissolution in serodiscordant couples for the propagation of HIV.
Methods
We develop a compartmental model to study epidemic outcomes of elevated partnership dissolution rates in serodiscordant couples and parameterize it with estimates from population-based data (Rakai, Uganda).
Results
Via its effect on partnership dissolution, every percentage point increase in HIV status awareness reduces HIV incidence in monogamous populations by 0.27 percent for women and 0.63 percent for men. These effects are even larger when the assumption of monogamy can be relaxed, but are moderated by other behavior changes (e.g., increased condom use) in HIV status aware serodiscordant partnerships. When these behavior changes are taken into account, each percentage point increase in HIV status awareness reduces HIV incidence by 0.13 and 0.32 percent for women and men, respectively (assuming monogamy). The partnership dissolution effect exists because it decreases the fraction of serodiscordant couples in the population and prolongs the time that individuals spend outside partnerships.
Conclusion
Our model predicts that elevated partnership dissolution rates in HIV status aware serodiscordant couples reduce the spread of HIV. As a consequence, the full impact of couples HTC for HIV prevention is probably larger than recognized to date. Particularly high partnership dissolution rates in female positive serodiscordant couples contribute to the gender imbalance in HIV infections.
doi:10.1371/journal.pone.0050669
PMCID: PMC3524232  PMID: 23284641
20.  Reproductive Counseling by Clinic Healthcare Workers in Durban, South Africa: Perspectives from HIV-Infected Men and Women Reporting Serodiscordant Partners 
Background. Understanding HIV-infected patient experiences and perceptions of reproductive counseling in the health care context is critical to inform design of effective pharmaco-behavioral interventions that minimize periconception HIV risk and support HIV-affected couples to realize their fertility goals. Methods. We conducted semistructured, in-depth interviews with 30 HIV-infected women (with pregnancy in prior year) and 20 HIV-infected men, all reporting serodiscordant partners and accessing care in Durban, South Africa. We investigated patient-reported experiences with safer conception counseling from health care workers (HCWs). Interview transcripts were reviewed and coded using content analysis for conceptual categories and emergent themes. Results. The study findings indicate that HIV-infected patients recognize HCWs as a resource for periconception-related information and are receptive to speaking to a HCW prior to becoming pregnant, but seldom seek or receive conception advice in the clinic setting. HIV nondisclosure and unplanned pregnancy are important intervening factors. When advice is shared, patients reported receiving a range of information. Male participants showed particular interest in accessing safer conception information. Conclusions. HIV-infected men and women with serodiscordant partners are receptive to the idea of safer conception counseling. HCWs need to be supported to routinely initiate accurate safer conception counseling with HIV-infected patients of reproductive age.
doi:10.1155/2012/146348
PMCID: PMC3426202  PMID: 22927713
21.  Characteristics of HIV-1 Serodiscordant Couples Enrolled in a Clinical Trial of Antiretroviral Pre-Exposure Prophylaxis for HIV-1 Prevention 
PLoS ONE  2011;6(10):e25828.
Introduction
Stable heterosexual HIV-1 serodiscordant couples in Africa have high HIV-1 transmission rates and are a critical population for evaluation of new HIV-1 prevention strategies. The Partners PrEP Study is a randomized, double-blind, placebo-controlled trial of tenofovir and emtricitabine-tenofovir pre-exposure prophylaxis to decrease HIV-1 acquisition within heterosexual HIV-1 serodiscordant couples. We describe the trial design and characteristics of the study cohort.
Methods
HIV-1 serodiscordant couples, in which the HIV-1 infected partner did not meet national guidelines for initiation of antiretroviral therapy, were enrolled at 9 research sites in Kenya and Uganda. The HIV-1 susceptible partner was randomized to daily oral tenofovir, emtricitabine-tenofovir, or matching placebo with monthly follow-up for 24–36 months.
Results
From July 2008 to November 2010, 7920 HIV-1 serodiscordant couples were screened and 4758 enrolled. For 62% (2966/4758) of enrolled couples, the HIV-1 susceptible partner was male. Median age was 33 years for HIV-1 susceptible and HIV-1 infected partners [IQR (28–40) and (26–39) respectively]. Most couples (98%) were married, with a median duration of partnership of 7.0 years (IQR 3.0–14.0) and recent knowledge of their serodiscordant status [median 0.4 years (IQR 0.1–2.0)]. During the month prior to enrollment, couples reported a median of 4 sex acts (IQR 2–8); 27% reported unprotected sex and 14% of male and 1% of female HIV-1 susceptible partners reported sex with outside partners. Among HIV-1 infected partners, the median plasma HIV-1 level was 3.94 log10 copies/mL (IQR 3.31–4.53) and median CD4 count was 496 cells/µL (IQR 375–662); the majority (64%) had WHO stage 1 HIV-1 disease.
Conclusions
Couples at high risk of HIV-1 transmission were rapidly recruited into the Partners PrEP Study, the largest efficacy trial of oral PrEP. (ClinicalTrials.gov NCT00557245)
doi:10.1371/journal.pone.0025828
PMCID: PMC3187805  PMID: 21998703
22.  Circumcision of Male Children for Reduction of Future Risk for HIV: Acceptability among HIV Serodiscordant Couples in Kampala, Uganda 
PLoS ONE  2011;6(7):e22254.
Introduction
The ultimate success of medical male circumcision for HIV prevention may depend on targeting male infants and children as well as adults, in order to maximally reduce new HIV infections into the future.
Methods
We conducted a cross-sectional study among heterosexual HIV serodiscordant couples (a population at high risk for HIV transmission) attending a research clinic in Kampala, Uganda on perceptions and attitudes about medical circumcision for male children for HIV prevention. Correlates of willingness to circumcise male children were assessed using generalized estimating equations methods.
Results
318 HIV serodiscordant couples were interviewed, 51.3% in which the female partner was HIV uninfected. Most couples were married and cohabiting, and almost 50% had at least one uncircumcised male child of ≤18 years of age. Overall, 90.2% of male partners and 94.6% of female partners expressed interest in medical circumcision for their male children for reduction of future risk for HIV infection, including 79.9% of men and 87.6% of women who had an uncircumcised male child. Among both men and women, those who were knowledgeable that circumcision reduces men's risk for HIV (adjusted prevalence ratio [APR] 1.34 and 1.14) and those who had discussed the HIV prevention effects of medical circumcision with their partner (APR 1.08 and 1.07) were significantly (p≤0.05) more likely to be interested in male child circumcision for HIV prevention. Among men, those who were circumcised (APR 1.09, p = 0.004) and those who were HIV seropositive (APR 1.09, p = 0.03) were also more likely to be interested in child circumcision for HIV prevention.
Conclusions
A high proportion of men and women in Ugandan heterosexual HIV serodiscordant partnerships were willing to have their male children circumcised for eventual HIV prevention benefits. Engaging both parents may increase interest in medical male circumcision for HIV prevention.
doi:10.1371/journal.pone.0022254
PMCID: PMC3140501  PMID: 21799805
23.  Intimate partner sexual and physical violence among women in Togo, West Africa: Prevalence, associated factors, and the specific role of HIV infection 
Global Health Action  2014;7:10.3402/gha.v7.23456.
Background
A substantial proportion of newly diagnosed HIV infections in sub-Saharan Africa occur within serodiscordant cohabiting heterosexual couples. Intimate partner violence is a major concern for couple-oriented HIV preventive approaches. This study aimed at estimating the prevalence and associated factors of intimate partner physical and sexual violence among HIV-infected and -uninfected women in Togo. We also described the severity and consequences of this violence as well as care-seeking behaviors of women exposed to intimate partner violence.
Methods
A cross-sectional survey was conducted between May and July 2011 within Sylvanus Olympio University Hospital in Lomé. HIV-infected women attending HIV care and uninfected women attending postnatal care and/or children immunization visits were interviewed. Intimate partner physical and sexual violence and controlling behaviors were assessed using an adapted version of the WHO Multi-country study on Women’s Health and Life Events questionnaire.
Results
Overall, 150 HIV-uninfected and 304 HIV-infected women accepted to be interviewed. The prevalence rates of lifetime physical and sexual violence among HIV-infected women were significantly higher than among uninfected women (63.1 vs. 39.3%, p<0.01 and 69.7 vs. 35.3%, p<0.01, respectively). Forty-two percent of the women reported having ever had physical injuries as a consequence of intimate partner violence. Among injured women, only one-third had ever disclosed real causes of injuries to medical staff and none of them had been referred to local organizations to receive appropriate psychological support. Regardless of HIV status and after adjustment on potential confounders, the risk of intimate partner physical and sexual violence was strongly and significantly associated with male partner multi-partnership and early start of sexual life. Among uninfected women, physical violence was significantly associated with gender submissive attitudes.
Discussion and conclusions
The prevalence rates of both lifetime physical and sexual violence were very high among HIV-uninfected women and even higher among HIV-infected women recruited in health facilities in this West African country. Screening for intimate partner violence should be systematic in health-care settings, and specifically within HIV care services. At a time of increased investments in couple-oriented HIV prevention interventions, further longitudinal research to better understanding of HIV-serodiscordant couple dynamics in terms of intimate partner violence is needed.
doi:10.3402/gha.v7.23456
PMCID: PMC4036383  PMID: 24866864
intimate partner violence; gender; HIV infection; Africa
24.  Genital herpes 
Clinical Evidence  2011;2011:1603.
Introduction
Genital herpes is an infection with herpes simplex virus type 1 (HSV-1) or type 2 (HSV-2), and is among the most common sexually transmitted diseases.
Methods and outcomes
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of interventions to prevent sexual transmission of herpes simplex virus? What are the effects of interventions to prevent transmission of herpes simplex virus from mother to neonate? What are the effects of antiviral treatment in people with a first episode of genital herpes? What are the effects of interventions to reduce the impact of recurrence? What are the effects of treatments in people with genital herpes and HIV? We searched: Medline, Embase, The Cochrane Library, and other important databases up to January 2010 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
Results
We found 35 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
Conclusions
In this systematic review we present information relating to the effectiveness and safety of the following interventions: antivirals, caesarean delivery, condoms, oral aciclovir, psychotherapy, recombinant glycoprotein vaccines, serological screening, and counselling.
Key Points
Genital herpes is an infection with herpes simplex virus type 1 (HSV-1) or type 2 (HSV-2). The typical clinical features include painful shallow anogenital ulceration. It is among the most common sexually transmitted diseases, with up to 23% of adults in the UK and US having antibodies to HSV-2.
Genital herpes, like other genital ulcer diseases, is a significant risk factor for acquiring HIV for both men and women. People with HIV can have severe herpes outbreaks, and this may help facilitate transmission of both herpes and HIV infections to others.
Oral antiviral treatment of someone who is seropositive for HSV seems to be effective in reducing transmission to a previously uninfected partner.
Despite limited evidence, male condom use is generally believed to reduce sexual transmission of herpes from infected men to uninfected sexual partners. We don't know, based specifically on evidence in serodiscordant couples, how effective male condom use is at preventing transmission from infected women to uninfected men. However, based on observational data and clinical experience of the effects of condoms to prevent acquisition of genital herpes in uninfected people, there is consensus that they are likely to be beneficial in preventing transmission from infected women to their uninfected partners.We didn't find any evidence examining the effectiveness of female condoms in preventing transmission.
Recombinant glycoprotein vaccines do not seem any more effective than placebo in preventing transmission to people at high risk from infection. We did not find any evidence about other vaccines.
We found insufficient evidence to draw reliable conclusions on whether antiviral maintenance treatment in late pregnancy, or serological screening and counselling to prevent acquisition of herpes in late pregnancy are effective in preventing transmission of HSV from mother to neonate. Caesarean delivery in women with genital lesions at term may reduce the risk of transmission, but is associated with an increased risk of maternal morbidity and mortality.
Oral antiviral treatments effectively decrease symptoms in people with first episodes of genital herpes, although we found insufficient evidence to establish which type of oral antiviral drug was most effective.
If herpes is recurrent, aciclovir, famciclovir, and valaciclovir when taken at the start of recurrence are all equally beneficial in reducing duration of symptoms, lesion healing time, and viral shedding. Daily maintenance treatment with oral antiviral agents effectively reduces frequency of recurrences, and improves quality of life.We don't know whether psychotherapy is effective in reducing recurrence.
Oral antiviral treatments are likely to be effective in treating recurrent episodes of genital herpes in people with HIV, and are generally believed to be useful in treating first episodes of genital herpes in people with HIV, although evidence supporting this is sparse. Oral antiviral treatments are also likely to be effective in preventing recurrence of genital herpes in people with HIV.
PMCID: PMC3217751  PMID: 21496359
25.  Outside Sexual Partnerships and Risk of HIV Acquisition for HIV Uninfected Partners in African HIV Serodiscordant Partnerships 
Background
As African countries scale up couples HIV testing, little is known about sexual behaviors and HIV risk for HIV uninfected partners in known HIV serodiscordant relationships.
Methods
We conducted a prospective study of 3,380 HIV serodiscordant partnerships from 7 African countries. Self-reported sexual behavior data were collected quarterly from HIV uninfected partners.
Results
The proportion of HIV uninfected partners reporting sex with their known primary HIV infected partner decreased during follow-up (from 93.5% in the prior month at baseline to 73.2% at 24 months, p<0.001). Simultaneously, an increasing proportion reported sex with an outside partner (from 3.1% to 13.9%, p<0.001). A small proportion (<5%, stable throughout follow-up) reported sex with the infected partner and an outside partner in the same month (concurrent). Unprotected sex was more common with outside partners than with their primary known HIV infected partners (risk ratio 4.6; 95% CI 4.2–5.2). HIV incidence was similar for those reporting sex only with their primary HIV infected partner compared to those who reported an outside partner (2.87 vs. 3.02 per 100 person-years, p=0.7), although those who had outside partners were more likely to acquire HIV that was virologically distinct from that of their primary partner (p<0.001).
Conclusion
For uninfected members of HIV serodiscordant couples, sex with the infected partner declined as sex with outside partners increased, likely reflecting relationship dissolution and risk shifting from a known infected partner. Risk reduction messages for HIV uninfected partners in serodiscordant partnerships should include strategies to reduce HIV acquisition from outside partners.
doi:10.1097/QAI.0b013e318237b864
PMCID: PMC3237862  PMID: 21963939
HIV serodiscordant couples; sexual behavior; condom use

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