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1.  FSWs Typology and Condoms Use Among HIV High Risk Groups in Sindh, Pakistan: A Developing Country Perspective 
Objective
We aimed to determine the association of FSWs typology with condom use among HIV high risk groups in Sindh, Pakistan
Introduction
HIV is growing rapidly worldwide resulting in estimated 34 million population [1]. Recently, its epidemic has spread in Africa, Latin America, and the Caribbean, and most parts of Asia [2]. According to Antenatal sero surveillance study conducted in 2011 by Agriteam canada, it’s prevalence in Pakistan is <0.1 [3].Focusing narrowly, its prevalence in Sindh, (one of the provinces of Pakistan) is similar in general population, but it is in the phase of concentrated epidemic (having more than 5% of prevalence in high risk groups)in vulnerable groups like IDUs and Male sex workers and transgender [4].
Sexual intercourse has been identified as major route especially in HIV high risk groups including male sex workers, female sex workers (FSWs), transgender (hijras) and IV drug users. Among them, FSWs are at high risk because of unprotected sex and illicit drug use. Their prevalence is found to be 30.7% in low and middle income countries [5]. South Asia contributed with 12.63 lakh FSW in India only [6]. On the basis of their station of work, they are categorized into facility based (kothikhana, brothel or home) and mobile (street, mobile or beggars). They use different preventive measures including condom for their protection from HIV [7]. It varies with availability and access [8] . FSWs typology have different cliental and mode of action, therefore, it important to explore the preventive methods.
Methods
Data was extracted from Second Generation Surveillance, Integrated behavioral and biological survey, Round IV for HIV infection conducted by Agriteam Canada in partnership with National AIDS Control Program, Pakistan in 2011. It was a cross sectional survey for high risk groups including FSWs from Pakistan. It was ethically approved by Review Board of the Public Health Agency of Canada and HOPE International’s Ethical Review Board, Pakistan. From Sindh province, FSWs based in Karachi, Sukkur and Larkana were recruited. Considering typology, they were categorized as mobile or facility based. After informed consent, socio-demographic and risk behavior were inquired. HIV was tested by ELISA/EIA and confirmed by Western Blot. Data was analyzed on SPSS 19. Continuous variables were expressed as mean±SD while categorical as frequency(%). Logistic regression assessed the association of FSWs typology with condoms use among HIV high risk groups.
Results
Out of 4567 high risk population, 1127 were identified as FSWs. Mean age was 26.9 years. Most of them were facility based (72.8%) and 81.3% used condoms. Typology, age, education, duration of involvement, number of client per day, number of paid oral sex per month, knowledge about STI and knowledge about drop in center were significantly associated with condom use among HIV high risk groups.
Conclusions
Majority of facility based FSWs use condoms to prevent HIV infection. Awareness and access to home based FSWs should be increased. It may help in targeting and designing preventive strategies for them at government and mass level.
PMCID: PMC3692789
FSW; typology; condoms; HIV high risk groups; Pakistan
2.  HIV-infected workers deported from the Gulf States: impact on southern Pakistan 
International journal of STD & AIDS  1999;10(12):812-814.
Summary
HIV prevalence is still very low in Pakistan, but its south Asian location and subgroups with recognized lifestyle risk factors suggest that Pakistan will experience expanded diffusion of HIV. We report the frequency of HIV infections identified by the AIDS Control Programme on the Sindh province of Pakistan. Most HIV-positive cases currently reported to the Sindh AIDS Control Programme are found among Pakistani workers deported from the Gulf States and among foreigners. The 58 returned workers with HIV represent 61 to 86% of reported cases in any given year during the 1996–1998 period. Five wives of returning workers have been identified with HIV. Expatriate workers in the Gulf States are tested for HIV routinely, unlike other subgroups in Pakistan. Considering the risk of HIV/AIDS due to regular introduction of HIV from returned workers, and the limited awareness surrounding sexual health and HIV/STD transmission issues in Pakistan, intervention programmes targeted at overseas workers need to be implemented to control the expansion of the HIV epidemic in Pakistan.
PMCID: PMC2564791  PMID: 10639063
HIV; acquired immunodeficiency syndrome; migration; Pakistan; surveillance; Middle East
3.  Antiretroviral Drug Resistance Mutations Among Treated and Treatment-Naive Patients in Pakistan: Diversity of the HIV Type 1 pol Gene in Pakistan 
AIDS Research and Human Retroviruses  2011;27(12):1277-1282.
Abstract
Pakistan is experiencing a growing HIV epidemic. Antiretroviral drugs (ARV) have been smuggled into the country and available without prescription since the early 1990s, but are now provided free of cost by the government. We assessed the prevalence of HIV-1, drug resistance, and subtype distributions. Blood specimens were collected from HIV-1-infected participants registered in Sindh Province on dry blood spot (DBS) cards in 2008. Pol, protease, and partial reverse transcriptase regions were sequenced after reverse transcriptase PCR (RT-PCR). HIV-1 subtype was assigned by phylogenetic analysis. Primary drug resistance was analyzed by the Calibrated Population Resistance (CPR) tool using the Stanford Surveillance Drug Resistance Mutation (SDRM) major mutation list. Out of 100 blood samples collected, 42 were suitable for testing. Out of 42, 11 were ARV-receiving and 31 ARV-naive patients. Among them, 24 were injection drug users (IDUs), four immigrants, two hijras (male transvestites), two men who have sex with men (MSM), four prisoners, one female sex workers, two spouses of HIV-infected persons, and four from the general population. ARV resistance among naive patients was 2/31 (6.5%) and 36.4% (4/11) among ARV-experienced patients making an overall resistance of 14.2%. HIV-1 subtype A1 was the predominant subtype found in 35/42 (83.3%) followed by CRF35_AD and C, 6.5% each. Subtype D and G were found in one (2.4%) each. A significant proportion of Pakistani HIV patients has ARV drug resistance. Physicians treating patients should consider the magnitude of drug resistance while selecting regimens, and address drug adherence aggressively.
doi:10.1089/aid.2010.0324
PMCID: PMC3227241  PMID: 21591988
4.  High risk behaviors of injection drug users registered with harm reduction programme in Karachi, Pakistan 
Background
Surveillance data of Sindh AIDS Control Programme, Pakistan suggest that HIV infection is rapidly increasing among IDUs in Karachi and has reached 9% in 2004–5 indicating that the country has progressed from nascent to concentrated level of HIV epidemic. Findings of 2nd generation surveillance in 2004–5 also indicate 104/395 (26.3%) IDUs HIV positive in the city.
Methods
We conducted a cross sectional study among registered IDUs of a needle exchange and harm reduction programme in Karachi, Pakistan. A total of 161 IDUs were included in the study between October–November 2003. A detailed questionnaire was implemented and blood samples were collected for HIV, hepatitis B & C and syphilis. HIV, hepatitis B and C antibody tests were performed using Enzyme Linked Immunosorbent Assay (ELISA) method. Syphilis tests (RPR & TPHA) were performed on Randox kit.
Besides calculating frequencies univariate analysis was performed using t tests for continuous variables as age, age at first intercourse and average age of initiation of addiction and chi square for categorical variables like paid for sex or not to identify risk factors for hepatitis B and C and syphilis.
Results
Average age of IDU was 35.9 years and average age of initiation of drugs was 15.9 years. Number of drug injections per day was 2.3. Shooting drugs in group sharing syringes was reported by 128 (79.5%) IDUs. Over half 94 (58.3%) reported paying for sex and 64% reported never using a condom. Commercial selling of blood was reported by 44 (28%). 1 of 161 was HIV positive (0.6%). The prevalence of hepatitis B was 12 (7.5%), hepatitis C 151 (94.3%) and syphilis 21 (13.1%). IDUs who were hepatitis C positive were more likely to start sexual activity at an earlier age and had never used condoms. Similarly IDUs who were hepatitis B positive were more likely to belong to a younger age group. Syphilis positive IDUs were more likely to have paid for sex and had never used a condom.
Conclusion
Prudent measures such as access to sterile syringes, rehabilitation and opiate substitution therapies are required to reduce high risk behaviors of IDUs in Pakistan.
doi:10.1186/1477-7517-4-7
PMCID: PMC1800841  PMID: 17291354
5.  The Uptake and Accuracy of Oral Kits for HIV Self-Testing in High HIV Prevalence Setting: A Cross-Sectional Feasibility Study in Blantyre, Malawi 
PLoS Medicine  2011;8(10):e1001102.
Augustine Choko and colleagues assess the uptake and acceptability of home-based supervised oral HIV self-testing in Malawi, demonstrating the feasibility of this approach in a high-prevalence, low-income environment.
Background
Although HIV testing and counseling (HTC) uptake has increased dramatically in Africa, facility-based services are unlikely to ever meet ongoing need to the full. A major constraint in scaling up community and home-based HTC services is the unacceptability of receiving HTC from a provider known personally to prospective clients. We investigated the potential of supervised oral HIV self-testing from this perspective.
Methods and Findings
Adult members of 60 households and 72 members of community peer groups in urban Blantyre, Malawi, were selected using population-weighted random cluster sampling. Participants were offered self-testing plus confirmatory HTC (parallel testing with two rapid finger-prick blood tests), standard HTC alone, or no testing. 283 (95.6%) of 298 selected adults participated, including 136 (48.0%) men. 175 (61.8%) had previously tested (19 known HIV positive), although only 64 (21.5%) within the last year. HIV prevalence was 18.5%. Among 260 (91.9%) who opted to self-test after brief demonstration and illustrated instructions, accuracy was 99.2% (two false negatives). Although 98.5% rated the test “not hard at all to do,” 10.0% made minor procedural errors, and 10.0% required extra help. Most participants indicated willingness to accept self-test kits, but not HTC, from a neighbor (acceptability 94.5% versus 46.8%, p = 0.001).
Conclusions
Oral supervised self-testing was highly acceptable and accurate, although minor errors and need for supervisory support were common. This novel option has potential for high uptake at local community level if it can be supervised and safely linked to counseling and care.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
According to the World Health Organization, despite the dramatic increase in the acceptability of HIV testing, more than 60% of people living with HIV do not know their status—a factor that is seriously hampering the global response to the HIV epidemic. The inconvenience and cost involved in visiting services in addition to a general aversion to visiting health facilities appear to be major barriers. Home-based HIV-testing services bypass these obstacles and are being adopted as national policy in a number of countries. However, given the tension between confidentiality and convenience, many people do not want to be counseled and tested by someone they know well, thus creating logistical difficulties and added costs to the provision of home-based testing services.
Why Was This Study Done?
Self-testing in private has considerable potential to contribute to first-time and repeat HIV testing but raises a number of issues, such as accuracy, the potential for adverse psychological reactions in the absence of face-to-face counseling, and the difficulty in organizing subsequent links to HIV/AIDS care. Self-testing has been used for over a decade in the US, but given the need to further scale up HIV testing and counseling in Africa, and to encourage regular repeat testing, the researchers conducted a mixed quantitative and qualitative study of self-testing for HIV using oral test kits to test whether supervised oral self-testing could yield accurate results. The researchers also wanted to explore reasons for accepting self-testing and respondents' preferences for HIV testing.
What Did the Researchers Do and Find?
The researchers conducted their study in four community health worker catchment areas in three high-density residential suburbs of Blantyre, Malawi. Between March and July 2010, the researchers randomly selected two groups of participants from within these catchment areas and all adults were then invited to participate in interview and optional HIV testing and counseling carried out in their home. Participants were offered the choice between self-test for HIV followed by standard voluntary counseling and testing, standard voluntary counseling and testing only, and no HIV testing or counseling. Pre-and post-test counseling was provided to all participants and after self-testing, a counselor reread the self-test kit, completed a checklist of potential errors and confirmed the result using two rapid HIV test kits run in parallel from a finger-prick blood specimen. All participants testing positive were referred to the nearest primary health center.
All 260 participants who consented to voluntary counseling and testing also opted to self-test, with the remaining 23 (8.1%) choosing not to test. HIV prevalence was 18.5% (48 of 260) and HIV prevalence among participants who had previously tested HIV-negative or not tested at all was 12.0% (29 of 241 participants) meaning that less than half of HIV-infected participants were previously diagnosed, and just over half of undiagnosed HIV infections were in individuals who had previously tested HIV negative. The researchers found self-testing to be highly accurate, with clear and concordant results for 256 (99.2%) of 258 participants with both self-test and blood results. Overall sensitivity for self-test self-read was 97.9% with specificity of 100%. At exit interview, 256 (98.5%) of participants rated self-testing as “very easy” to do but additional help was requested by 26 (10%) of self test participants and procedural errors were identified for 26 participants (10%). Importantly, self-testing was the preferred option for future HIV tests for 56.4% of participants and the most common choice for both men and women.
What Do These Findings Mean?
The findings of this study show that self-testing for HIV (after a brief demonstration and illustrated instructions) is highly accurate and is widely accepted by the community, indicating that there is strong community readiness to adopt self-testing alongside other HIV counseling and testing strategies in high HIV prevalence settings in urban Africa. Self-testing may prove especially valuable for encouraging regular repeat testing, couple testing, and first-time testing in otherwise hard-to-reach groups such as men and older individuals. Finally, given the accuracy achieved and strong preferences around future testing, further exploration of self-testing options could help to make progress towards meeting universal access goals.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001102.
This study is further discussed in a PLoS Medicine Perspective by Walensky and Bassett
Recently published WHO Guidelines explain the principles and processes of adapting HIV guidelines into national programs
The U.S. Centers for Disease Control's initiative Act against AIDS has some user-friendly information on the different types of HIV tests available
A WHO document discusses existing practices and surrounding issues related with HIV self-testing among health workers in sub-Saharan Africa
doi:10.1371/journal.pmed.1001102
PMCID: PMC3186813  PMID: 21990966
6.  Comparing risk factors of HIV among hijra sex workers in Larkana and other cities of Pakistan: an analytical cross sectional study 
BMC Public Health  2012;12:279.
Background
In 2005, Pakistan was first labeled as a country with concentrated epidemic of Human Immunodeficiency Virus (HIV). This was revealed through second generation surveillance conducted by HIV/AIDS Surveillance Project (HASP). While injection drug users (IDUs) were driving the epidemic, subsequent surveys showed that Hijra (transgender) sex workers (HSWs) were emerging as the second most vulnerable group with an average national prevalence of 6.4%. An exceptionally high prevalence (27.6%) was found in Larkana, which is a small town on the right bank of river Indus near the ruins of Mohenjo-Daro in the province of Sindh. This paper presents the risk factors associated with high prevalence of HIV among HSWs in Larkana as compared to other cities of the country.
Methods
Data were extracted for secondary analysis from 2008 Integrated behavioral and biological survey (IBBS) to compare HSWs living in Larkana with those living in other cities including Karachi and Hyderabad in Sindh; Lahore and Faisalabad in Punjab; and Peshawar in Khyber Pakhtunkhwa provinces. After descriptive analysis, univariate and multivariate analyses were performed to identify risk factors. P value of 0.25 or less was used to include factors in multivariate analysis.
Results
We compared 199 HSWs from Larkana with 420 HSWs from other cities. The average age of HSWs in Larkana was 26.42 (±5.4) years. Majority were Sindhi speaking (80%), uneducated (68%) and unmarried (97%). In univariate analysis, factors associated with higher prevalence of HIV in Larkana included younger age i.e. 20–24 years (OR: 5.8, CI: 2.809–12.15), being unmarried (OR: 2.4, CI: 1.0–5.7), sex work as the only mode of income (OR: 5.5, CI: 3.70–8.2) and longer duration of being involved in sex work 5–10 years (OR: 3.3, CI: 1.7–6.12). In multivariate logistic regression the HSWs from Larkana were more likely to lack knowledge regarding preventive measures against HIV (OR 11.9, CI: 3.4–41.08) and were more prone to use of alcohol during anal intercourse (OR: 6.3, CI: 2.77–17.797).
Conclusion
Outreach programs focusing on safer sexual practices and VCT are urgently needed to address the upsurge of HIV among HSWs in Larkana.
doi:10.1186/1471-2458-12-279
PMCID: PMC3418161  PMID: 22490045
Commercial sex workers; HIV prevalence; Urban Sindh
7.  Are HIV Epidemics among Men Who Have Sex with Men Emerging in the Middle East and North Africa?: A Systematic Review and Data Synthesis 
PLoS Medicine  2011;8(8):e1000444.
A systematic review by Laith Abu-Raddad and colleagues collates and analyzes the epidemiology of HIV among men who have sex with men in Middle Eastern and North African countries.
Background
Men who have sex with men (MSM) bear a disproportionately higher burden of HIV infection than the general population. MSM in the Middle East and North Africa (MENA) are a largely hidden population because of a prevailing stigma towards this type of sexual behavior, thereby limiting the ability to assess infection transmission patterns among them. It is widely perceived that data are virtually nonexistent on MSM and HIV in this region. The objective of this review was to delineate, for the first time, the evidence on the epidemiology of HIV among MSM in MENA.
Methods and Findings
This was a systematic review of all biological, behavioral, and other related data on HIV and MSM in MENA. Sources of data included PubMed (Medline), international organizations' reports and databases, country-level reports and databases including governmental and nongovernmental organization publications, and various other institutional documents. This review showed that onsiderable data are available on MSM and HIV in MENA. While HIV prevalence continues at low levels among different MSM groups, HIV epidemics appear to be emerging in at least few countries, with a prevalence reaching up to 28% among certain MSM groups. By 2008, the contribution of MSM transmission to the total HIV notified cases increased and exceeded 25% in several countries. The high levels of risk behavior (4–14 partners on average in the last six months among different MSM populations) and of biomarkers of risks (such as herpes simplex virus type 2 at 3%–54%), the overall low rate of consistent condom use (generally below 25%), the relative frequency of male sex work (20%–76%), and the substantial overlap with heterosexual risk behavior and injecting drug use suggest potential for further spread.
Conclusions
This systematic review and data synthesis indicate that HIV epidemics appear to be emerging among MSM in at least a few MENA countries and could already be in a concentrated state among several MSM groups. There is an urgent need to expand HIV surveillance and access to HIV testing, prevention, and treatment services in a rapidly narrowing window of opportunity to prevent the worst of HIV transmission among MSM in the Middle East and North Africa.
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, as the disease rapidly spread, it became clear that AIDS also affects heterosexual men and women. Now three decades on, more than 30 million people are infected with HIV, the virus that causes AIDS. HIV is most often spread by having unprotected sex with an infected partner and, globally, 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, a term that encompasses homosexual, bisexual, and transgender men, and heterosexual men who sometimes have sex with men). In some countries, male-to-male sexual contact remains the most important transmission route. Moreover, although the global prevalence of HIV infection (the proportion the world's population infected with HIV) has stabilized, the prevalence of HIV infection among MSM seems to be increasing in multiple countries and new and resurgent HIV epidemics among MSM populations are being frequently reported.
Why Was This Study Done?
In the US and the UK, the MSM population is visible and has helped to raise awareness about the risks of HIV transmission through male-to-male sexual contact. In many other countries, MSM are much less visible, fearing discrimination, stigmatization (being considered socially unacceptable) or arrest. In the Middle East and North Africa (MENA, a geographical region that encompasses countries that share historical, socio-cultural, linguistic and religious characteristics), MSM are the most hidden HIV risk group. Consequently, very little is known about HIV transmission patterns among MSM in MENA. Indeed, it is widely thought that there is virtually no information available on the epidemiology (causes, distribution, and control) of HIV among MSM in this region. In this systematic review and data synthesis, the researchers use predefined search criteria to identify all the published and unpublished data on the epidemiology of HIV among MSM in MENA and combine (synthesize) these data to produce a coherent picture of the HIV epidemic in this potentially key group of people for HIV transmission in this region.
What Did the Researchers Do and Find?
The researchers identified 26 articles and 51 other country-level reports and sources of data that included data on the prevalence of male-to-male sexual contact, HIV transmission, levels of high-risk behavior, and the extent of knowledge about HIV among MSM in MENA. The prevalence of HIV infection among MSM was low in most countries but high in others. For example, the infection rate in Pakistan was 27.6% among one MSM group. Importantly, there was some evidence of increasing HIV prevalence and emerging epidemics among MSM in the region. Thus, by 2008, MSM transmission was responsible for more than a quarter of notified cases of HIV in several countries. Worryingly, MSM were involved in several types of HIV-related high risk behavior. For example, they had, on average, between 4 and 14 sexual partners in the past six months, their rates of consistent condom use were generally below 25% and, in some countries, MSM frequently reported injecting drug use, another common mode of HIV transmission. In addition, 20%–75.5% of MSM exchanged sex for money and contact between MSM and female sex workers and other female sexual partners was often common. Finally, although the level of basic knowledge about HIV/AIDS was high, the level of comprehensive knowledge was limited with a high proportion of MSM perceiving their risk of contracting HIV as low.
What Do These Findings Mean?
These findings indicate that there is considerable and increasing data about HIV transmission and risk behavior among MSM in MENA. However, the quality of this evidence varies greatly. Little has been collected over time in individual populations and, because only the visible part of the MSM populations in many MENA countries has been sampled, these findings may not be representative of all MSM in this region. Nevertheless, these findings suggest that HIV epidemics are emerging among MSM in several MENA countries. Importantly, the high levels of risk behaviors practiced by many MSM in MENA mean that MSM could become the pivotal risk group for HIV transmission in this region in the next decade. There is, therefore, an urgent need to expand HIV surveillance and access to HIV testing, prevention and treatment services among MSM in this region to limit the size of the HIV epidemic.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000444.
Information about the status of the HIV epidemic in the Middle East and North Africa can be found in the World Bank/UNAIDS/WHO report Characterizing the HIV/AIDS epidemic in the Middle East and North Africa: Time for strategic action
Information about the global HIV epidemic among men who have sex with men can be found in the World Bank report The Global HIV Epidemics among Men Who Have Sex with Men
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 information on HIV transmission and transmission in gay men and other MSM and on safer sex
Information is available from Avert, an international AIDS charity, on all aspects of HIV/AIDS, including information on HIV, AIDS and men who have sex with men and on HIV and AIDS prevention (in English and Spanish)
The US Centers for Disease Control and Prevention also have information about HIV/AIDS among men who have sex with men (in English and Spanish)
doi:10.1371/journal.pmed.1000444
PMCID: PMC3149074  PMID: 21829329
8.  Prevalence of head lice and hygiene practices among women over twelve years of age in Sindh, Balochistan, and North West Frontier Province: National Health Survey of Pakistan, 1990-1994 
Parasites & Vectors  2011;4:11.
Background
Head lice infestation is an infection of the scalp and skin which causes blood loss, discomfort, and social and psychological distress with the possibility of secondary bacterial infections occurring at scratch sites. In Pakistan, although some small scale studies have been conducted to investigate prevalence of head lice in school children and the general population, no population based estimates have been reported. The National Health Survey of Pakistan (NHSP 1990 - 94) was a nationally representative health examination survey of the Pakistani population. The NHSP is the first population based household survey to collect data on the prevalence of head lice in adult women in Pakistan. In this paper we use data from the NHSP to present an epidemiological profile of personal hygiene practices and head lice infestation among women aged 12 years or older in three provinces of Pakistan; Balochistan, Sindh and North West Frontier Province (NWFP).
Results
Overall about 7% women aged 12 years and older suffered from head lice infestation. Multivariable logistic regression analysis identified factors independently associated with presence of head lice. Age less than 16 years and crowding at home were associated with higher infestation-rates. The impact of household socio-economic status on infestation rates among women was different in urban and rural settings; urban women with low socio-economic status were more vulnerable than similar women in rural settings. Bathing infrequently in summer was associated with higher prevalence rates only in Sindh, possibly due to the fact that among the three provinces Sindh has a hotter and more humid summer.
Conclusions
The results of our analysis of NHSP indicate high levels of head lice infestation among girls and women in the three Provinces. The epidemiological profile of hygienic practices of women indicated that NWFP and Balochistan as compared to Sindh, and rural as compared to urban areas were less developed with respect to access to water supply and soap for maintaining personal hygiene. Simple and cost-effective measures such as provision of water and soap, and improving awareness regarding maintaining personal hygiene can contribute significantly towards improving public health status of the women in Pakistan.
doi:10.1186/1756-3305-4-11
PMCID: PMC3040706  PMID: 21288357
9.  HIV among People Who Inject Drugs in the Middle East and North Africa: Systematic Review and Data Synthesis 
PLoS Medicine  2014;11(6):e1001663.
Laith Abu-Raddad and colleagues assess the current state of knowledge of the HIV epidemic among people who inject drugs in the Middle East and North Africa.
Please see later in the article for the Editors' Summary
Background
It is perceived that little is known about the epidemiology of HIV infection among people who inject drugs (PWID) in the Middle East and North Africa (MENA). The primary objective of this study was to assess the status of the HIV epidemic among PWID in MENA by describing HIV prevalence and incidence. Secondary objectives were to describe the risk behavior environment and the HIV epidemic potential among PWID, and to estimate the prevalence of injecting drug use in MENA.
Methods and Findings
This was a systematic review following the PRISMA guidelines and covering 23 MENA countries. PubMed, Embase, regional and international databases, as well as country-level reports were searched up to December 16, 2013. Primary studies reporting (1) the prevalence/incidence of HIV, other sexually transmitted infections, or hepatitis C virus (HCV) among PWIDs; or (2) the prevalence of injecting or sexual risk behaviors, or HIV knowledge among PWID; or (3) the number/proportion of PWID in MENA countries, were eligible for inclusion. The quality, quantity, and geographic coverage of the data were assessed at country level. Risk of bias in predefined quality domains was described to assess the quality of available HIV prevalence measures. After multiple level screening, 192 eligible reports were included in the review. There were 197 HIV prevalence measures on a total of 58,241 PWID extracted from reports, and an additional 226 HIV prevalence measures extracted from the databases.
We estimated that there are 626,000 PWID in MENA (range: 335,000–1,635,000, prevalence of 0.24 per 100 adults). We found evidence of HIV epidemics among PWID in at least one-third of MENA countries, most of which are emerging concentrated epidemics and with HIV prevalence overall in the range of 10%–15%. Some of the epidemics have however already reached considerable levels including some of the highest HIV prevalence among PWID globally (87.1% in Tripoli, Libya). The relatively high prevalence of sharing needles/syringes (18%–28% in the last injection), the low levels of condom use (20%–54% ever condom use), the high levels of having sex with sex workers and of men having sex with men (15%–30% and 2%–10% in the last year, respectively), and of selling sex (5%–29% in the last year), indicate a high injecting and sexual risk environment. The prevalence of HCV (31%–64%) and of sexually transmitted infections suggest high levels of risk behavior indicative of the potential for more and larger HIV epidemics.
Conclusions
Our study identified a large volume of HIV-related biological and behavioral data among PWID in the MENA region. The coverage and quality of the data varied between countries. There is robust evidence for HIV epidemics among PWID in multiple countries, most of which have emerged within the last decade and continue to grow. The lack of sufficient evidence in some MENA countries does not preclude the possibility of hidden epidemics among PWID in these settings. With the HIV epidemic among PWID in overall a relatively early phase, there is a window of opportunity for prevention that should not be missed through the provision of comprehensive programs, including scale-up of harm reduction services and expansion of surveillance systems.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
About 35 million people worldwide are currently infected with HIV, the virus that causes AIDS, and around 2.3 million people become newly infected every year. HIV is mainly transmitted through unprotected sex with an infected partner. However, people who inject drugs (PWID) have a particularly high risk of HIV infection because blood transfer through needle and syringe sharing can transmit the virus. Worldwide, 5%–10% of all HIV-positive people are PWID but in some regions of the world the fraction of all HIV-positive people that are PWID is even higher. To meet the global health challenge of the high HIV prevalence (the proportion of a population that has a specific disease) among PWID, the Joint United Nations Programme on HIV/AIDS (UNAIDS) and other international bodies endorse harm reduction strategies to prevent risky injection behaviors among PWID. These strategies include education and the provision of clean needles, syringes, and opioid substitution therapy.
Why Was This Study Done?
To maximize the effect of these harm-reduction strategies in specific regions, it is important to understand the status of the HIV epidemic among PWID. Although surveillance systems provide the information on HIV infection needed to track the progress of HIV epidemics among PWID in many regions, little is known about the HIV epidemic among PWID in the Middle East and North Africa (MENA, a geographical region that encompasses countries that share historical, socio-cultural, linguistic, and religious characteristics). Several factors contribute to the likelihood of individuals injecting drugs in MENA. For example, Afghanistan (a MENA country) produces most of the world's supply of heroin, which is largely trafficked through Iran and Pakistan (also MENA countries). In this systematic review and data synthesis, the researchers use predefined criteria to identify all the published and unpublished data on HIV prevalence and incidence (the number of new cases of a disease in a population in a given time) among PWID in MENA and combine (synthesize) these data to assess the status of the HIV epidemic in this key population for HIV transmission in MENA.
What Did the Researchers Do and Find?
The researchers identified 192 reports that reported the prevalence/incidence of HIV, other sexually transmitted infections and infection with hepatitis C virus (HCV, another virus transmitted through drug injection) among PWID, the prevalence of injecting or sexual risk behaviors among PWID, or the number/proportion of PWID in MENA. From these data, the researchers estimated that there are about 600,000 PWID in MENA (a prevalence of 0.24 per 100 adults, which is comparable with figures from other regions). The data provided evidence for HIV epidemics among PWID in at least a third of MENA countries, mainly emerging concentrated epidemics (epidemics that are still growing but in which HIV infection and transmission are already considerable). HIV prevalence among PWID in MENA varied considerably, reaching an extremely high prevalence of 87.1% in Tripoli, Libya. The data also revealed a high injecting and sexual risk environment among PWID in MENA (for example, on average, about a quarter of PWID shared a needle or syringe in their most recent injection and only a third reported ever using condoms) that, together with a high prevalence of HCV and sexually transmitted infections among PWID, indicates the potential for more and larger HIV epidemics.
What Do These Findings Mean?
These findings indicate that substantial amounts of HIV-related data have been collected from PWID in MENA but that the coverage and quality of these data vary widely between countries. They provide robust evidence for growing HIV epidemics, most of which have emerged within the past decade, among PWID in several MENA countries, but do not preclude the possibility of hidden epidemics among PWID in additional MENA countries. Overall, these findings suggest that the HIV epidemic among PWID in MENA is at a relatively early stage. This window of opportunity to control the emerging epidemics should not be missed, warn the researchers. HIV surveillance among PWID in MENA must be expanded to detect and monitor emerging and growing HIV epidemics, they suggest, and to inform effective HIV policy and programming. Improvements in HIV prevention and treatment among PWID in MENA are essential, they conclude, to confront the growing HIV problem in this population and, to prevent the onward transmission of HIV from PWID to other population groups.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001663.
A 2010 report produced by the World Bank, UNAIDS, and WHO provides information on the status of the HIV epidemic in the Middle East and North Africa; the UNAIDS Middle East and North Africa Regional Report on AIDS 2011 provides further information
The 2013 UNAIDS World AIDS Day Report provides up-to-date information about the AIDS epidemic and efforts to halt it
The Middle East and North Africa Harm Reduction Association (MENAHRA) provides information about harm reduction efforts, services, and programs in the Middle East and North Africa; Harm Reduction International provides information about harm reduction concepts, strategies, programs, and publications globally
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 people who inject drugs and HIV/AIDS and on harm reduction and HIV prevention (in English and Spanish)
The US National Institute on Drug Abuse also provides information about drug abuse and HIV/AIDS (in English and Spanish)
Personal stories about living with HIV/AIDS are available through Avert, Nam/aidsmap, and Healthtalkonline
doi:10.1371/journal.pmed.1001663
PMCID: PMC4061009  PMID: 24937136
10.  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
11.  Comparison of Xpert MTB/RIF with Other Nucleic Acid Technologies for Diagnosing Pulmonary Tuberculosis in a High HIV Prevalence Setting: A Prospective Study 
PLoS Medicine  2011;8(7):e1001061.
In this prospective, real-world cohort study nested within a national screening program for tuberculosis, Lesley Scott and colleagues compare the performance of Xpert MTB/RIF on a single sputum sample with different TB sputum detection technologies.
Background
The Xpert MTB/RIF (Cepheid) non-laboratory-based molecular assay has potential to improve the diagnosis of tuberculosis (TB), especially in HIV-infected populations, through increased sensitivity, reduced turnaround time (2 h), and immediate identification of rifampicin (RIF) resistance. In a prospective clinical validation study we compared the performance of Xpert MTB/RIF, MTBDRplus (Hain Lifescience), LightCycler Mycobacterium Detection (LCTB) (Roche), with acid fast bacilli (AFB) smear microscopy and liquid culture on a single sputum specimen.
Methods and Findings
Consecutive adults with suspected TB attending a primary health care clinic in Johannesburg, South Africa, were prospectively enrolled and evaluated for TB according to the guidelines of the National TB Control Programme, including assessment for smear-negative TB by chest X-ray, clinical evaluation, and HIV testing. A single sputum sample underwent routine decontamination, AFB smear microscopy, liquid culture, and phenotypic drug susceptibility testing. Residual sample was batched for molecular testing. For the 311 participants, the HIV prevalence was 70% (n = 215), with 120 (38.5%) culture-positive TB cases. Compared to liquid culture, the sensitivities of all the test methodologies, determined with a limited and potentially underpowered sample size (n = 177), were 59% (47%–71%) for smear microscopy, 76% (64%–85%) for MTBDRplus, 76% (64%–85%) for LCTB, and 86% (76%–93%) for Xpert MTB/RIF, with specificities all >97%. Among HIV+ individuals, the sensitivity of the Xpert MTB/RIF test was 84% (69%–93%), while the other molecular tests had sensitivities reduced by 6%. TB detection among smear-negative, culture-positive samples was 28% (5/18) for MTBDRplus, 22% (4/18) for LCTB, and 61% (11/18) for Xpert MTB/RIF. A few (n = 5) RIF-resistant cases were detected using the phenotypic drug susceptibility testing methodology. Xpert MTB/RIF detected four of these five cases (fifth case not tested) and two additional phenotypically sensitive cases.
Conclusions
The Xpert MTB/RIF test has superior performance for rapid diagnosis of Mycobacterium tuberculosis over existing AFB smear microscopy and other molecular methodologies in an HIV- and TB-endemic region. Its place in the clinical diagnostic algorithm in national health programs needs exploration.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Tuberculosis (TB)—a contagious bacterial infection that mainly affects the lungs—is a global public health problem. In 2009, 9.4 million people developed TB, and 1.7 million people died from the disease; a quarter of these deaths were in HIV-positive individuals. People who are infected with HIV, the virus that causes AIDS, are particularly susceptible to TB because of their weakened immune system. Consequently, TB is a leading cause of illness and death among people living with HIV. TB is caused by Mycobacterium tuberculosis, which is spread in airborne droplets when people with the disease cough or sneeze. Its characteristic symptoms are a persistent cough, night sweats, and weight loss. Diagnostic tests for TB include sputum smear analysis (the microscopic examination of mucus brought up from the lungs by coughing for the presence of M. tuberculosis) and mycobacterial liquid culture (in which bacteriologists try to grow M. tuberculosis from sputum samples and test its drug sensitivity). TB can usually be cured by taking several powerful drugs daily for at least six months.
Why Was This Study Done?
Mycobacterial culture is a sensitive but slow way to diagnose TB. To halt the disease's spread, it is essential that TB—particularly TB that is resistant to several treatment drugs (multidrug-resistant, or MDR, TB)—is diagnosed quickly. Recently, several nucleic acid amplification technology (NAAT) tests have been developed that rapidly detect M. tuberculosis DNA in patient samples and look for DNA changes that make M. tuberculosis drug-resistant. In December 2010, the World Health Organization (WHO) endorsed Xpert MTB/RIF—an automated DNA test that detects M. tuberculosis and rifampicin resistance (an indicator of MDR TB) within two hours—for the investigation of patients who might have TB, especially in regions where MDR TB and HIV infection are common. TB diagnosis in HIV-positive people can be difficult because they are more likely to have smear-negative TB than HIV-negative individuals. In this prospective study, the researchers compare the performance of Xpert MTB/RIF on a single sputum sample with that of smear microscopy, liquid culture, and two other NAAT tests (MTBDRplus and LightCycler Mycobacterium Detection) in adults who might have TB in Johannesburg (South Africa), a region where many adults are HIV-positive.
What Did the Researchers Do and Find?
The researchers evaluated adults with potential TB attending a primary health care clinic for TB according to national guidelines and determined their HIV status. A sputum sample from 311 participants underwent smear microscopy, liquid culture, and drug susceptibility testing; 177 samples were also tested for TB using NAAT tests. They found that 70% of the participants were HIV-positive and 38.5% had culture-positive TB. Compared to liquid culture, smear microscopy, MTBDRplus, LightCycler Mycobacterium Detection, and Xpert MTB/RIF had sensitivities of 59%, 76%, 76%, and 86%, respectively. That is, assuming that liquid culture detected everyone with TB, Xpert MTB/RIF detected 86% of the cases. The specificity of all the tests compared to liquid culture was greater than 97%. That is, they all had a low false-positive rate. Among people who were HIV-positive, the sensitivity of Xpert MTB/RIF was 84%; the sensitivities of the other NAAT tests were 70%. Moreover, Xpert MTB/RIF detected TB in 61% of smear-negative, culture-positive samples, whereas the other NAATs detected TB in only about a quarter of these samples. Finally, although some TB cases were identified as drug-resistant by one test but drug-sensitive by another, the small number of drug-resistant cases means no firm conclusions can be made about the accuracy of drug resistance determination by the various tests.
What Do These Findings Mean?
Although these findings are likely to be affected by the study's small size, they suggest that Xpert MTB/RIF may provide a more accurate rapid diagnosis of TB than smear microscopy and other currently available NAAT tests in regions where HIV and TB are endemic (i.e., always present). Indeed, the reported accuracy of Xpert MTB/RIF for TB diagnosis—85% sensitivity and 97% specificity—has the potential to save more than 400,000 lives per year. Taken together with the results of other recent studies (including an accompanying article by Lawn et al. that investigates the use of Xpert MTB/RIF for screening for HIV-associated TB and rifampicin resistance), these findings support the WHO recommendation that Xpert MTB/RIF, rather than smear microscopy, should be the initial test in HIV-infected individuals who might have TB.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001061.
This study is further discussed in a PLoS Medicine Perspective by Carlton Evans; a related PLoS Medicine Research Article by Lawn et al. is also available
WHO provides information (in several languages) on all aspects of tuberculosis, including general information on tuberculosis diagnostics and specific information on the Xpert MTB/RIF test; further information about WHO's endorsement of Xpert MTB/RIF is included in a recent Strategic and Technical Advisory Group for Tuberculosis report
WHO also provides information about tuberculosis and HIV
The US National Institute of Allergy and Infectious Diseases has detailed information on tuberculosis and HIV/AIDS
The US Centers for Disease Control and Prevention also has information about tuberculosis, including information on the diagnosis of and on tuberculosis and HIV co-infection
Information is available from Avert, an international AIDS charity on many aspects of HIV/AIDS, including information on HIV-related tuberculosis (in English and Spanish)
doi:10.1371/journal.pmed.1001061
PMCID: PMC3144192  PMID: 21814495
12.  Antiretroviral Therapy for Prevention of Tuberculosis in Adults with HIV: A Systematic Review and Meta-Analysis 
PLoS Medicine  2012;9(7):e1001270.
In a systematic review and meta-analysis, Amitabh Suthar and colleagues investigate the association between antiretroviral therapy and the reduction in the incidence of tuberculosis in adults with HIV infection.
Background
Human immunodeficiency virus (HIV) infection is the strongest risk factor for developing tuberculosis and has fuelled its resurgence, especially in sub-Saharan Africa. In 2010, there were an estimated 1.1 million incident cases of tuberculosis among the 34 million people living with HIV worldwide. Antiretroviral therapy has substantial potential to prevent HIV-associated tuberculosis. We conducted a systematic review of studies that analysed the impact of antiretroviral therapy on the incidence of tuberculosis in adults with HIV infection.
Methods and Findings
PubMed, Embase, African Index Medicus, LILACS, and clinical trial registries were systematically searched. Randomised controlled trials, prospective cohort studies, and retrospective cohort studies were included if they compared tuberculosis incidence by antiretroviral therapy status in HIV-infected adults for a median of over 6 mo in developing countries. For the meta-analyses there were four categories based on CD4 counts at antiretroviral therapy initiation: (1) less than 200 cells/µl, (2) 200 to 350 cells/µl, (3) greater than 350 cells/µl, and (4) any CD4 count.
Eleven studies met the inclusion criteria. Antiretroviral therapy is strongly associated with a reduction in the incidence of tuberculosis in all baseline CD4 count categories: (1) less than 200 cells/µl (hazard ratio [HR] 0.16, 95% confidence interval [CI] 0.07 to 0.36), (2) 200 to 350 cells/µl (HR 0.34, 95% CI 0.19 to 0.60), (3) greater than 350 cells/µl (HR 0.43, 95% CI 0.30 to 0.63), and (4) any CD4 count (HR 0.35, 95% CI 0.28 to 0.44). There was no evidence of hazard ratio modification with respect to baseline CD4 count category (p = 0.20).
Conclusions
Antiretroviral therapy is strongly associated with a reduction in the incidence of tuberculosis across all CD4 count strata. Earlier initiation of antiretroviral therapy may be a key component of global and national strategies to control the HIV-associated tuberculosis syndemic.
Review Registration
International Prospective Register of Systematic Reviews CRD42011001209
Please see later in the article for the Editors' Summary.
Editors' Summary
Background
Tuberculosis—a contagious bacterial infection— is a global public-health problem. In 2010, 8.8 million people developed active tuberculosis and 1.4 million people died from the disease. Tuberculosis can be cured by taking powerful antibiotics regularly for several months, and between 1995 and 2010, 46 million people with tuberculosis were successfully treated using DOTS—a directly observed antibiotic regimen designed by the World Health Organization (WHO). Now, though, the HIV epidemic is compromising global tuberculosis control efforts. HIV-positive people are very susceptible to tuberculosis because HIV, the virus that causes AIDS, destroys the immune system cells (including CD4 lymphocytes) that normally combat tuberculosis. In 2010, 1.1 million of the new (incident) cases of tuberculosis were among the 34 million people living with HIV, and 350,000 people died of HIV-associated tuberculosis, making tuberculosis the leading cause of death among HIV-positive people. To tackle HIV-associated tuberculosis, which occurs mainly in developing countries, WHO now recommends that HIV and tuberculosis programs use collaborative approaches such as the Three I's for HIV/TB strategy—intensified tuberculosis case-finding among HIV-positive people, isoniazid preventative therapy for HIV-positive people without active tuberculosis, and (tuberculosis) infection control in healthcare facilities, social settings, and households.
Why Was This Study Done?
Despite progress in scaling up the Three I's for HIV/TB strategy, complementary interventions are still needed to prevent tuberculosis in HIV-positive people. Antiretroviral therapy (ART) lowers the viral load of people infected with HIV and restores their immune system function and could, therefore, prevent HIVassociated tuberculosis, in addition to treating HIV infection. WHO recommends ART for all HIV-positive adults with a CD4 count of less than 350 cells/μl of blood and for all HIVpositive, tuberculosis-positive individuals irrespective of their CD4 count. However, the evidence for ART's preventative impact on tuberculosis has not been systematically examined. Here, the researchers undertake a systematic review (a search that uses predefined criteria to identify all the research on a given topic) and a meta-analysis (a statistical method for combining the results of studies) to investigate the impact of ART initiated at various CD4 counts on the development of tuberculosis in HIV-positive adults in developing countries.
What Did the Researchers Do and Find?
The researchers found 11 studies that compared tuberculosis incidence by ART status in HIV-infected adults over periods longer than six months on average in developing countries and undertook meta-analyses of these studies based on four categories of CD4 count at ART initiation (less than 200 cells/μl, 200–350 cells/μl, greater than 350 cells/μl, and any CD4 count). For all these categories, ART was strongly associated with a reduction in the incidence of tuberculosis. For example, the meta-analysis of the two studies that reported on participants in whom ART was initiated at a CD4 count less than 200 cells/μl yielded a hazard ratio (HR) of 0.16. That is, study participants starting ART when their CD4 count was below 200 cells/μl were about one-sixth as likely to develop tuberculosis as participants not receiving ART. In the metaanalysis of all 11 studies, study participants receiving ART were about one-third as likely to develop tuberculosis as study participants receiving no ART, irrespective of their CD4 count (HR 0.35). Importantly, the CD4 count at which ART was initiated did not significantly alter the magnitude of ART's preventive effect on tuberculosis development.
What Do These Findings Mean?
These findings suggest that ART is strongly associated with a reduction in the incidence of tuberculosis in HIV-positive adults in developing countries, whatever the CD4 count at ART initiation. Because most of the studies in this meta-analysis were observational, these results do not show that ART causes a reduction in tuberculosis incidence—other unknown factors shared by the study participants who received ART may be responsible for their lower tuberculosis incidence. Moreover, factors such as variations in diagnostic methods among the studies included in this meta-analysis may have affected the accuracy of these findings. Nevertheless, the key finding that ART is associated with a significant reduction in tuberculosis cases among adults with CD4 counts greater than 350 cells//μl should be considered by healthcare providers, policymakers, and people living with HIV when weighing the benefits and risks of early ART initiation. It also suggests that early ART initiation (in combination with expanded HIV testing) could be a key component of future global and national strategies to control HIV-associated tuberculosis.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001270.
WHO provides information on all aspects of tuberculosis, including information on tuberculosis and HIV, on the Three I's for HIV/TB, and on ART for tuberculosis prevention (some information is in several languages)
The TB/HIV Working Group is part of the Stop TB Partnership, which is working toward tuberculosis elimination; patient stories about tuberculosis/HIV co-infection are also available on their site
The US Centers for Disease Control and Prevention has information about tuberculosis and about tuberculosis and HIV co-infection
The US National Institute of Allergy and Infectious Diseases also has detailed information on all aspects of tuberculosis including HIV-associated tuberculosis
Information is available from Avert, an international AIDS charity, on HIV-related tuberculosis (in English and Spanish), and from Aidsmap, a non-governmental organization, on HIV-associated tuberculosis
doi:10.1371/journal.pmed.1001270
PMCID: PMC3404110  PMID: 22911011
13.  Supervised and Unsupervised Self-Testing for HIV in High- and Low-Risk Populations: A Systematic Review 
PLoS Medicine  2013;10(4):e1001414.
By systematically reviewing the literature, Nitika Pant Pai and colleagues assess the evidence base for HIV self tests both with and without supervision.
Background
Stigma, discrimination, lack of privacy, and long waiting times partly explain why six out of ten individuals living with HIV do not access facility-based testing. By circumventing these barriers, self-testing offers potential for more people to know their sero-status. Recent approval of an in-home HIV self test in the US has sparked self-testing initiatives, yet data on acceptability, feasibility, and linkages to care are limited. We systematically reviewed evidence on supervised (self-testing and counselling aided by a health care professional) and unsupervised (performed by self-tester with access to phone/internet counselling) self-testing strategies.
Methods and Findings
Seven databases (Medline [via PubMed], Biosis, PsycINFO, Cinahl, African Medicus, LILACS, and EMBASE) and conference abstracts of six major HIV/sexually transmitted infections conferences were searched from 1st January 2000–30th October 2012. 1,221 citations were identified and 21 studies included for review. Seven studies evaluated an unsupervised strategy and 14 evaluated a supervised strategy. For both strategies, data on acceptability (range: 74%–96%), preference (range: 61%–91%), and partner self-testing (range: 80%–97%) were high. A high specificity (range: 99.8%–100%) was observed for both strategies, while a lower sensitivity was reported in the unsupervised (range: 92.9%–100%; one study) versus supervised (range: 97.4%–97.9%; three studies) strategy. Regarding feasibility of linkage to counselling and care, 96% (n = 102/106) of individuals testing positive for HIV stated they would seek post-test counselling (unsupervised strategy, one study). No extreme adverse events were noted. The majority of data (n = 11,019/12,402 individuals, 89%) were from high-income settings and 71% (n = 15/21) of studies were cross-sectional in design, thus limiting our analysis.
Conclusions
Both supervised and unsupervised testing strategies were highly acceptable, preferred, and more likely to result in partner self-testing. However, no studies evaluated post-test linkage with counselling and treatment outcomes and reporting quality was poor. Thus, controlled trials of high quality from diverse settings are warranted to confirm and extend these findings.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
About 34 million people (most living in resource-limited countries) are currently infected with HIV, the virus that causes AIDS, and about 2.5 million people become infected with HIV every year. HIV is usually transmitted through unprotected sex with an infected partner. HIV infection is usually diagnosed by looking for antibodies to HIV in blood or saliva. Early during infection, the immune system responds to HIV by beginning to make antibodies that recognize the virus and target it for destruction. “Seroconversion”—the presence of detectable amounts of antibody in the blood or saliva—usually takes 6–12 weeks. Rapid antibody-based tests, which do not require laboratory facilities, can provide a preliminary result about an individual's HIV status from a simple oral swab or finger stick sample within 20 minutes. However preliminary rapid positive results have to be confirmed in a laboratory, which may take a few days or weeks. If positive, HIV infection can be controlled but not cured by taking a daily cocktail of powerful antiretroviral drugs throughout life.
Why Was This Study Done?
To reduce the spread of HIV, it is essential that HIV-positive individuals get tested, change behaviors avoid transmitting the virus to other people by, for example, always using a condom during sex, and if positive get on to treatment that is available worldwide. Treatment also reduces transmission of virus to the partner and controls the virus in the community. However, only half the people currently living with HIV know their HIV status, a state of affairs that increases the possibility of further HIV transmission to their partners and children. HIV positive individuals are diagnosed late with advanced HIV infection that costs health care services. Although health care facility-based HIV testing has been available for decades, people worry about stigma, visibility, and social discrimination. They also dislike the lack of privacy and do not like having to wait for their test results. Self-testing (i.e., self-test conduct and interpretation) might alleviate some of these barriers to testing by allowing individuals to determine their HIV status in the privacy of their home and could, therefore, increase the number of individuals aware of their HIV status. This could possibly reduce transmission and, through seeking linkages to care, bring HIV under control in communities. In some communities and countries, stigma of HIV prevents people from taking action about their HIV status. Indeed, an oral (saliva-based) HIV self-test kit is now available in the US. But how acceptable, feasible, and accurate is self-testing by lay people, and will people who find themselves self-test positive seek counseling and treatment? In this systematic review (a study that uses pre-defined criteria to identify all the research on a given topic), the researchers examine these issues by analyzing data from studies that have evaluated supervised self-testing (self-testing and counseling aided by a health-care professional) and unsupervised self-testing (self-testing performed without any help but with counseling available by phone or internet).
What Did the Researchers Do and Find?
The researchers identified 21 eligible studies, two-thirds of which evaluated oral self-testing and a third of which evaluated blood-based self-testing. Seven studies evaluated an unsupervised self-testing strategy and 14 evaluated a supervised strategy. Most of the data (89%) came from studies undertaken in high-income settings. The study populations varied from those at high risk of HIV infection to low-risk general populations. Across the studies, acceptability (defined as the number of people who actually self-tested divided by the number who consented to self-test) ranged from 74% to 96%. With both strategies, the specificity of self-testing (the chance of an HIV-negative person receiving a negative test result is true negative) was high but the sensitivity of self-testing (the chance of an HIV-positive person receiving a positive test result is indeed a true positive) was higher for supervised than for unsupervised testing. The researchers also found evidence that people preferred self-testing to facility-based testing and oral self-testing to blood-based self testing and, in one study, 96% of participants who self-tested positive sought post-testing counseling.
What Do These Findings Mean?
These findings provide new but limited information about the feasibility, acceptability, and accuracy of HIV self-testing. They suggest that it is feasible to implement both supervised and unsupervised self-testing, that both strategies are preferred to facility-based testing, but that the accuracy of self-testing is variable. However, most of the evidence considered by the researchers came from high-income countries and from observational studies of varying quality, and data on whether people self-testing positive sought post-testing counseling (linkage to care) were only available from one evaluation of unsupervised self-testing in the US. Consequently, although these findings suggest that self-testing could engage individuals in finding our their HIV status and thereby help modify behavior thus, reduce HIV transmission in the community, by increasing the proportion of people living with HIV who know their HIV status. The researchers suggested that more data from diverse settings and preferably from controlled randomized trials must be collected before any initiatives for global scale-up of self-testing for HIV infection are implemented.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001414.
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 HIV testing, and on HIV transmission and testing (in English and Spanish)
The UK National Health Service Choices website provides information about all aspects of HIV and AIDS; a “behind the headlines” article provides details about the 2012 US approval for an over-the-counter HIV home-use test
The 2012 World AIDS Day Report provides information about the percentage of people living with HIV who are aware of their HIV status in various African countries, as well as up-to-date information about the AIDS epidemic
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 getting a diagnosis
doi:10.1371/journal.pmed.1001414
PMCID: PMC3614510  PMID: 23565066
14.  A Model for the Roll-Out of Comprehensive Adult Male Circumcision Services in African Low-Income Settings of High HIV Incidence: The ANRS 12126 Bophelo Pele Project 
PLoS Medicine  2010;7(7):e1000309.
Bertrand Auvert and colleagues describe the large-scale roll-out of adult male circumcision through a program in South Africa.
Background
World Health Organization (WHO)/Joint United Nations Programme on AIDS (UNAIDS) has recommended adult male circumcision (AMC) for the prevention of heterosexually acquired HIV infection in men from communities where HIV is hyperendemic and AMC prevalence is low. The objective of this study was to investigate the feasibility of the roll-out of medicalized AMC according to UNAIDS/WHO operational guidelines in a targeted African setting.
Methods and Findings
The ANRS 12126 “Bophelo Pele” project was implemented in 2008 in the township of Orange Farm (South Africa). It became functional in 5 mo once local and ethical authorizations were obtained. Project activities involved community mobilization and outreach, as well as communication approaches aimed at both men and women incorporating broader HIV prevention strategies and promoting sexual health. Free medicalized AMC was offered to male residents aged 15 y and over at the project's main center, which had been designed for low-income settings. Through the establishment of an innovative surgical organization, up to 150 AMCs under local anesthesia, with sterilized circumcision disposable kits and electrocautery, could be performed per day by three task-sharing teams of one medical circumciser and five nurses. Community support for the project was high. As of November 2009, 14,011 men had been circumcised, averaging 740 per month in the past 12 mo, and 27.5% of project participants agreed to be tested for HIV. The rate of adverse events, none of which resulted in permanent damage or death, was 1.8%. Most of the men surveyed (92%) rated the services provided positively. An estimated 39.1% of adult uncircumcised male residents have undergone surgery and uptake is steadily increasing.
Conclusion
This study demonstrates that a quality AMC roll-out adapted to African low-income settings is feasible and can be implemented quickly and safely according to international guidelines. The project can be a model for the scale-up of comprehensive AMC services, which could be tailored for other rural and urban communities of high HIV prevalence and low AMC rates in Eastern and Southern Africa.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Acquired immunodeficiency syndrome (AIDS) has killed about 25 million people since 1981, and more than 30 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. Consequently, prevention of HIV infection 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 one or a few partners, and by always using a male or female condom. In addition, three trials in sub-Saharan Africa recently reported that medicalized adult male circumcision (AMC)—the surgical removal of the foreskin, a loose fold of skin that covers the head of the penis—can reduce HIV transmission rates in men by more than a half. Thus, AMC delivered as a catch-up campaign—in the long-term, circumcision of male infants is likely to be a more sustainable strategy—has the potential to reduce the prevalence of HIV (the proportion of the population infected with HIV) in sub-Saharan Africa.
Why Was This Study Done?
The World Health Organization (WHO) and the Joint United Nations Programme on AIDS (UNAIDS) now recommend that AMC programs should be rolled-out wherever there is a generalized HIV epidemic and few men are circumcised. Accordingly, these organizations have defined a minimum package of AMC services and have issued guidelines and tools designed to engage communities in the roll-out and to ensure that appropriate AMC counseling and surgical facilities are available. But is rapid AMC roll-out feasible in real-life settings? Here, the researchers try to find out by studying the “Bophelo Pele” (Health First) project. This project, which follows the WHO/UNAIDS guidelines for AMC, aims to offer free, safe AMC services to all men aged 15 years or more living in the Orange Farm township in South Africa as part of a community-based intervention against HIV. Orange Farm is in a low-income region of South Africa where HIV prevalence is 15.2% and AMC prevalence is about 25%.
What Did the Researchers Do and Find?
Before the Bophelo Pele project started in January 2008, the researchers consulted the community about the implementation of AMC, helped to create a community advisory board, organized community workshops to discuss the project, and surveyed people's knowledge about AMC and willingness to undergo AMC. These activities indicated a high level of community support for the project and a high level of willingness among men to undergo AMC. Once the project started, the researchers used multiple communication channels to tell the Orange Farm residents about AMC and broader HIV prevention strategies and provided eligible men with counseling about AMC and with voluntary HIV counseling and testing during the recruitment process. Three days after recruitment, eligible men were circumcised free-of-charge at the project's main center, where three teams of one medical circumciser and five nurses were able to complete up to 150 AMCs per day. By November 2009, 14,011 men had been circumcised (more than a third of the eligible men in the township), and AMC uptake was still increasing steadily. Nearly all the men circumcised over one 2-month period rated the AMC services positively in a survey and adverse effects (all mild) occurred after fewer than 1 in 50 circumcisions.
What Do These Findings Mean?
These findings suggest that the rapid roll-out of high-quality, free AMC as an intervention against HIV has been successful in the Orange Farm township. However, other findings highlight some of the challenges that face AMC roll-out. For example, only a quarter of the participants agreed to voluntary HIV counseling and testing, which is worrying because newly circumcised HIV-positive men have an increased risk of transmitting HIV if they resume sexual activity too soon after the operation. Similarly, only two-thirds of the participants returned for a check-up after circumcision; this proportion needs to be increased to ensure the safety and efficacy of AMC programs. Nevertheless, these findings and those from similar intervention programs in Kenya and Uganda indicate that AMC scale-up should be feasible, at least in the short term, as an HIV prevention strategy in low-income communities where there is a high HIV prevalence and a low AMC rate.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000309.
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
Information is available from Avert, an international AIDS charity on many aspects of HIV/AIDS, including information on HIV and AIDS in South Africa, and on circumcision and HIV (in English and Spanish)
More information about male circumcision is available from WHO and from the Clearinghouse on Male Circumcision, including a June 2010 report from WHO/UNAIDS entitled Progress in male circumcision scale-up: country implementation and research update
More information about the Bophelo Pele project is available
doi:10.1371/journal.pmed.1000309
PMCID: PMC2907271  PMID: 20652013
15.  HIV-1 Transmission during Early Infection in Men Who Have Sex with Men: A Phylodynamic Analysis 
PLoS Medicine  2013;10(12):e1001568.
Erik Volz and colleagues use HIV genetic information from a cohort of men who have sex with men in Detroit, USA to dissect the timing of onward transmission during HIV infection.
Please see later in the article for the Editors' Summary
Background
Conventional epidemiological surveillance of infectious diseases is focused on characterization of incident infections and estimation of the number of prevalent infections. Advances in methods for the analysis of the population-level genetic variation of viruses can potentially provide information about donors, not just recipients, of infection. Genetic sequences from many viruses are increasingly abundant, especially HIV, which is routinely sequenced for surveillance of drug resistance mutations. We conducted a phylodynamic analysis of HIV genetic sequence data and surveillance data from a US population of men who have sex with men (MSM) and estimated incidence and transmission rates by stage of infection.
Methods and Findings
We analyzed 662 HIV-1 subtype B sequences collected between October 14, 2004, and February 24, 2012, from MSM in the Detroit metropolitan area, Michigan. These sequences were cross-referenced with a database of 30,200 patients diagnosed with HIV infection in the state of Michigan, which includes clinical information that is informative about the recency of infection at the time of diagnosis. These data were analyzed using recently developed population genetic methods that have enabled the estimation of transmission rates from the population-level genetic diversity of the virus. We found that genetic data are highly informative about HIV donors in ways that standard surveillance data are not. Genetic data are especially informative about the stage of infection of donors at the point of transmission. We estimate that 44.7% (95% CI, 42.2%–46.4%) of transmissions occur during the first year of infection.
Conclusions
In this study, almost half of transmissions occurred within the first year of HIV infection in MSM. Our conclusions may be sensitive to un-modeled intra-host evolutionary dynamics, un-modeled sexual risk behavior, and uncertainty in the stage of infected hosts at the time of sampling. The intensity of transmission during early infection may have significance for public health interventions based on early treatment of newly diagnosed individuals.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Since the first recorded case of AIDS in 1981, the number of people infected with HIV, the virus that causes AIDS, has risen steadily. About 34 million people are currently HIV-positive, and about 2.5 million people become newly infected with HIV every year. Because HIV is usually transmitted through unprotected sex with an infected partner, individuals can reduce their risk of infection by abstaining from sex, by having only one or a few partners, and by always using condoms. Most people do not become ill immediately after infection with HIV, although some develop a short flu-like illness. The next stage of HIV infection, which may last more than ten years, also has no major symptoms, but during this stage, HIV slowly destroys immune system cells. Eventually, the immune system can no longer fight off infections by other disease-causing organisms, and HIV-positive people then develop one or more life-threatening AIDS-defining conditions, including unusual infections and specific types of cancer. HIV infection can be controlled, but not cured, by taking a daily cocktail of antiretroviral drugs.
Why Was This Study Done?
The design of effective programs to prevent the spread of HIV/AIDS depends on knowing how HIV transmissibility varies over the course of HIV infection. Consider, for example, a prevention strategy that focuses on increasing treatment rates: antiretroviral drugs, in addition to reducing illness and death among HIV-positive people, reduce HIV transmission from HIV-positive individuals. “Treatment as prevention” can only block transmissions that occur after diagnosis and entry into care. However, the transmissibility of HIV per sexual contact depends on a person's viral load, which peaks during early HIV infection, when people are often unaware of their HIV status and may still be following the high-risk patterns of sexual behavior that caused their own infection. Epidemiological surveillance data (information on HIV infections within populations) can be used to estimate how many new HIV infections occur within a population annually (HIV incidence) and the proportion of the population that is HIV-positive (HIV prevalence), but cannot be used to estimate the timing of transmission events. In this study, the researchers use “phylodynamic analysis” to estimate HIV incidence and prevalence and the timing of HIV transmission during infection. HIV, like many other viruses, rapidly accumulates genetic changes. The timing of transmission influences the pattern of these changes. Viral phylodynamic analysis—the quantitative study of how epidemiological, immunological, and evolutionary processes shape viral phylogenies (evolutionary trees)—can therefore provide estimates of transmission dynamics.
What Did the Researchers Do and Find?
The researchers obtained HIV sequence data (collected for routine surveillance of antiretroviral resistance mutations) and epidemiological surveillance data (including information on the stage of infection at diagnosis) for 662 HIV-positive men who have sex with men living in the Detroit metropolitan area of Michigan. They constructed a phylogenetic tree from the sequences using a “relaxed clock” approach and then fitted an epidemiological model (a mathematical model that represents the progress of individual patients through various stages of HIV infection) to the sequence data. Their approach, which integrates surveillance data and genetic data, yielded estimates of HIV incidence and prevalence among the study population similar to those obtained from surveillance data alone. However, it also provided information about HIV transmission that could not be obtained from surveillance data alone. In particular, it allowed the researchers to estimate that, in the current HIV epidemic among men who have sex with men in Detroit, 44.7% of HIV transmissions occur during the first year of infection.
What Do These Findings Mean?
The robustness of these findings depends on the validity of the assumptions included in the researchers' population genetic model and on the accuracy of the data fed into the model, and may not be generalizable to other cities or to other risk groups. Nevertheless, the findings of this analysis, which can be repeated in any setting where HIV sequence data for individual patients can be linked to patient-specific clinical and behavioral information, have important implications for HIV control strategies based on the early treatment of newly diagnosed individuals. Because relatively few infected individuals are diagnosed during early HIV infection, when the HIV transmission rate is high, it is unlikely, suggest the researchers, that the “treatment as prevention” strategy will effectively control the spread of HIV unless there are very high rates of HIV testing and treatment.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001568.
This study is further discussed in a PLOS Medicine Perspective by Timothy Hallett
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 HIV treatment as prevention (in English and Spanish)
The PLOS Medicine Collection Investigating the Impact of Treatment on New HIV Infections provides more information about HIV treatment as prevention
A PLOS Computational Biology Topic Page (a review article that is a published copy of record of a dynamic version of the article as found in Wikipedia) about viral phylodynamics is available
The US National Institute of Health–funded HIV Sequence Database contains HIV sequences and tools to analyze these sequences
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.1001568
PMCID: PMC3858227  PMID: 24339751
16.  Feasibility, Yield, and Cost of Active Tuberculosis Case Finding Linked to a Mobile HIV Service in Cape Town, South Africa: A Cross-sectional Study 
PLoS Medicine  2012;9(8):e1001281.
Katharina Kranzer and colleagues investigate the operational characteristics of an active tuberculosis case-finding service linked to a mobile HIV testing unit that operates in underserviced areas in Cape Town, South Africa.
Background
The World Health Organization is currently developing guidelines on screening for tuberculosis disease to inform national screening strategies. This process is complicated by significant gaps in knowledge regarding mass screening. This study aimed to assess feasibility, uptake, yield, treatment outcomes, and costs of adding an active tuberculosis case-finding program to an existing mobile HIV testing service.
Methods and Findings
The study was conducted at a mobile HIV testing service operating in deprived communities in Cape Town, South Africa. All HIV-negative individuals with symptoms suggestive of tuberculosis, and all HIV-positive individuals regardless of symptoms were eligible for participation and referred for sputum induction. Samples were examined by microscopy and culture. Active tuberculosis case finding was conducted on 181 days at 58 different sites. Of the 6,309 adults who accessed the mobile clinic, 1,385 were eligible and 1,130 (81.6%) were enrolled. The prevalence of smear-positive tuberculosis was 2.2% (95% CI 1.1–4.0), 3.3% (95% CI 1.4–6.4), and 0.4% (95% CI 1.4 015–6.4) in HIV-negative individuals, individuals newly diagnosed with HIV, and known HIV, respectively. The corresponding prevalence of culture-positive tuberculosis was 5.3% (95% CI 3.5–7.7), 7.4% (95% CI 4.5–11.5), 4.3% (95% CI 2.3–7.4), respectively. Of the 56 new tuberculosis cases detected, 42 started tuberculosis treatment and 34 (81.0%) completed treatment. The cost of the intervention was US$1,117 per tuberculosis case detected and US$2,458 per tuberculosis case cured. The generalisability of the study is limited to similar settings with comparable levels of deprivation and TB and HIV prevalence.
Conclusions
Mobile active tuberculosis case finding in deprived populations with a high burden of HIV and tuberculosis is feasible, has a high uptake, yield, and treatment success. Further work is now required to examine cost-effectiveness and affordability and whether and how the same results may be achieved at scale.
Editors' Summary
Background
In 2010, 8.8 million people developed active tuberculosis—a contagious bacterial infection—and 1.4 million people died from the disease. Most of these deaths were in low- and middle-income countries and a quarter were in HIV-positive individuals—people who are infected with HIV, the virus that causes AIDS, are particularly susceptible to tuberculosis because of their weakened immune system. Tuberculosis is caused by Mycobacterium tuberculosis, which is spread in airborne droplets when people with the disease cough or sneeze. Its characteristic symptoms are a persistent cough, unintentional weight loss, hemoptysis (coughing up blood from the lungs), fever, and night sweats. Diagnostic tests for tuberculosis include sputum smear microscopy (microscopic analysis of mucus brought up from the lungs by coughing) and culture (growth) of M. tuberculosis from sputum samples. Tuberculosis can be cured by taking several powerful antibiotics daily for at least 6 months.
Why Was This Study Done?
To improve tuberculosis control, active disease must be diagnosed quickly and treated immediately. Passive tuberculosis case finding, which relies on people seeking medical help because they feel unwell, delays the diagnosis and treatment of tuberculosis and increases M. tuberculosis transmission. By contrast, active tuberculosis case finding—where health workers seek out and diagnose individuals with TB who have not sought care on their own initiative—has the potential to reduce tuberculosis transmission by improving case detection. The World Health Organization (WHO), which already recommends active tuberculosis case finding in HIV-infected individuals as part of its HIV/TB “Three I's” strategy, is currently developing guidelines to inform the design of national tuberculosis screening strategies based on the local prevalence of HIV and TB and other context-specific factors that affect how many individuals need to be screened to identify each additional new tuberculosis case (the “yield” of active case finding). Large gaps in our knowledge about mass-screening strategies are complicating the development of these guidelines so, in this observational prospective study, the researchers assess the feasibility, uptake, yield, treatment outcomes, and costs of adding an active tuberculosis case-finding program to an existing mobile HIV testing service in South Africa.
What Did the Researchers Do and Find?
All HIVnegative adults with symptoms characteristic of tuberculosis and all HIV-positive adults regardless of symptoms who attended a mobile HIV testing service operating in deprived communities in ape Town, South Africa between May 2009 and February 2011 were eligible for inclusion in the study. Of the 6,309 adults who accessed the mobile clinic during this period, 1,385 met these eligibility criteria, and 1,130 were enrolled and referred for the collection of sputum samples, which were analyzed by microscopy and culture. The prevalence of smear-positive tuberculosis was 2.2%, 3.3%, and 0.4% among HIV-negative study participants, newly diagnosed HIV-positive participants, and people already known to have HIV, respectively. The corresponding prevalences for smear-negative/culture-positive tuberculosis were 5.3%, 7.4%, and 4.3%, respectively (culture detects more tuberculosis cases than microscopy but, whereas microscopy can provide a result within 1–2 days, culture can take several weeks). Fifty-six new tuberculosis cases were identified, 42 people started tuberculosis treatment, and 34 completed treatment (a treatment success rate of 81%). Finally, the incremental cost of the intervention was US$1,117 per tuberculosis case detected and US$2,458 per tuberculosis case cured.
What Do These Findings Mean?
These findings show that active case finding for tuberculosis delivered through a mobile HIV testing service is feasible and has a high uptake, yield and treatment success in deprived communities with a high prevalence of HIV and tuberculosis. The findings also highlight the challenges faced by mobile population-based services such as losses between tuberculosis diagnosis and treatment, which were greatest for smear-negative/culture-positive people who were more difficult to contact than smear-positive people because of the greater time lag between sputum collection and diagnosis. Because the study was done in a single city, these findings need to be confirmed in other settings—the yield of active tuberculosis case finding reported here, for example, is not likely to be generalizable to countries that rely on sputum smears for tuberculosis diagnosis. Finally, given that the incremental cost per case treated in this study is 3-fold higher than the incremental cost per case treated under passive case detection in South Africa, further studies are needed to determine the cost-effectiveness and affordability of population-based tuberculosis screening.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001281.
The World Health Organization provides information on all aspects of tuberculosis, including information on tuberculosis and HIV, and on the Three I?s for HIV/TB (some information is in several languages); details of a 2011 meeting on the development of guidelines on screening for active tuberculosis are available
The Stop TB partnership is working towards tuberculosis elimination; patient stories about tuberculosis/HIV coinfection are available
The US Centers for Disease Control and Prevention has information about tuberculosis, about tuberculosis and HIV co-infection, and about the diagnosis of tuberculosis disease
The US National Institute of Allergy and Infectious Diseases also has detailed information on all aspects of tuberculosis
MedlinePlus has links to further information about tuberculosis (in English and Spanish)
The Tuberculosis Survival Project, which aims to raise awareness of tuberculosis and provide support for people with tuberculosis, provides personal stories about treatment for tuberculosis; the Tuberculosis Vaccine Initiative also provides personal stories about dealing with tuberculosis
doi:10.1371/journal.pmed.1001281
PMCID: PMC3413719  PMID: 22879816
17.  Towards Universal Voluntary HIV Testing and Counselling: A Systematic Review and Meta-Analysis of Community-Based Approaches 
PLoS Medicine  2013;10(8):e1001496.
In a systematic review and meta-analysis, Amitabh Suthar and colleagues describe the evidence base for different HIV testing and counseling services provided outside of health facilities.
Please see later in the article for the Editors' Summary
Background
Effective national and global HIV responses require a significant expansion of HIV testing and counselling (HTC) to expand access to prevention and care. Facility-based HTC, while essential, is unlikely to meet national and global targets on its own. This article systematically reviews the evidence for community-based HTC.
Methods and Findings
PubMed was searched on 4 March 2013, clinical trial registries were searched on 3 September 2012, and Embase and the World Health Organization Global Index Medicus were searched on 10 April 2012 for studies including community-based HTC (i.e., HTC outside of health facilities). Randomised controlled trials, and observational studies were eligible if they included a community-based testing approach and reported one or more of the following outcomes: uptake, proportion receiving their first HIV test, CD4 value at diagnosis, linkage to care, HIV positivity rate, HTC coverage, HIV incidence, or cost per person tested (outcomes are defined fully in the text). The following community-based HTC approaches were reviewed: (1) door-to-door testing (systematically offering HTC to homes in a catchment area), (2) mobile testing for the general population (offering HTC via a mobile HTC service), (3) index testing (offering HTC to household members of people with HIV and persons who may have been exposed to HIV), (4) mobile testing for men who have sex with men, (5) mobile testing for people who inject drugs, (6) mobile testing for female sex workers, (7) mobile testing for adolescents, (8) self-testing, (9) workplace HTC, (10) church-based HTC, and (11) school-based HTC. The Newcastle-Ottawa Quality Assessment Scale and the Cochrane Collaboration's “risk of bias” tool were used to assess the risk of bias in studies with a comparator arm included in pooled estimates.
 117 studies, including 864,651 participants completing HTC, met the inclusion criteria. The percentage of people offered community-based HTC who accepted HTC was as follows: index testing, 88% of 12,052 participants; self-testing, 87% of 1,839 participants; mobile testing, 87% of 79,475 participants; door-to-door testing, 80% of 555,267 participants; workplace testing, 67% of 62,406 participants; and school-based testing, 62% of 2,593 participants. Mobile HTC uptake among key populations (men who have sex with men, people who inject drugs, female sex workers, and adolescents) ranged from 9% to 100% (among 41,110 participants across studies), with heterogeneity related to how testing was offered. Community-based approaches increased HTC uptake (relative risk [RR] 10.65, 95% confidence interval [CI] 6.27–18.08), the proportion of first-time testers (RR 1.23, 95% CI 1.06–1.42), and the proportion of participants with CD4 counts above 350 cells/µl (RR 1.42, 95% CI 1.16–1.74), and obtained a lower positivity rate (RR 0.59, 95% CI 0.37–0.96), relative to facility-based approaches. 80% (95% CI 75%–85%) of 5,832 community-based HTC participants obtained a CD4 measurement following HIV diagnosis, and 73% (95% CI 61%–85%) of 527 community-based HTC participants initiated antiretroviral therapy following a CD4 measurement indicating eligibility. The data on linking participants without HIV to prevention services were limited. In low- and middle-income countries, the cost per person tested ranged from US$2–US$126. At the population level, community-based HTC increased HTC coverage (RR 7.07, 95% CI 3.52–14.22) and reduced HIV incidence (RR 0.86, 95% CI 0.73–1.02), although the incidence reduction lacked statistical significance. No studies reported any harm arising as a result of having been tested.
Conclusions
Community-based HTC achieved high rates of HTC uptake, reached people with high CD4 counts, and linked people to care. It also obtained a lower HIV positivity rate relative to facility-based approaches. Further research is needed to further improve acceptability of community-based HTC for key populations. HIV programmes should offer community-based HTC linked to prevention and care, in addition to facility-based HTC, to support increased access to HIV prevention, care, and treatment.
Review Registration
International Prospective Register of Systematic Reviews CRD42012002554
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Three decades into the AIDS epidemic, about 34 million people (most living in resource-limited countries) are infected with HIV, the virus that causes AIDS. Every year another 2.2 million people become infected with HIV, usually through unprotected sex with an infected partner, and about 1.7 million people die. Infection with HIV, which gradually destroys the CD4 lymphocytes and other immune system cells that provide protection from life-threatening infections, is usually diagnosed by looking for antibodies to HIV in the blood or saliva. Disease progression is subsequently monitored in HIV-positive individuals by counting the CD4 cells in their blood. Initiation of antiretroviral drug therapy—a combination of drugs that keeps HIV replication in check but that does not cure the infection—is recommended when an individual's CD4 count falls below 500 cells/µl of blood or when he or she develops signs of severe or advanced disease, such as unusual infections.
Why Was This Study Done?
As part of intensified efforts to eliminate HIV/AIDS, United Nations member states recently set several HIV-related targets to be achieved by 2015, including reduced transmission of HIV and increased delivery of antiretroviral therapy. These targets can only be achieved if there is a large expansion in HIV testing and counseling (HTC) and increased access to HIV prevention and care services. The World Health Organization currently recommends that everyone attending a healthcare facility in regions where there is a generalized HIV epidemic (defined as when 1% or more of the general population is HIV-positive) should be offered HTC. However, many people rarely visit healthcare facilities, and others refuse “facility-based” HTC because they fear stigmatization and discrimination. Thus, facility-based HTC alone is unlikely to be sufficient to enable national and global HIV targets to be reached. In this systematic review and meta-analysis, the researchers evaluate the performance of community-based HTC approaches such as index testing (offering HTC to the sexual and injecting partners and household members of people with HIV), mobile testing (offering HTC through a service that visits shopping centers and other public facilities), and door-to-door testing (systematically offering HTC to homes in a catchment area). A systematic review uses predefined criteria to identify all the research on a given topic; meta-analysis combines the results of several studies.
What Did the Researchers Do and Find?
The researchers identified 117 studies (most undertaken in Africa and North America) involving 864,651 participants that evaluated community-based HTC approaches. Among these studies, the percentage of people offered community-based HTC who accepted it (HTC uptake) was 88% for index testing, 87% for self-testing, 80% for door-to-door testing, 67% for workplace testing, and 62% for school-based testing. Compared to facility-based approaches, community-based approaches increased the chances of an individual's CD4 count being above 350 cells/µl at diagnosis (an important observation because early diagnosis improves subsequent outcomes) but had a lower positivity rate, possibly because people with symptoms of HIV are more likely to visit healthcare facilities than healthy individuals. Importantly, 80% of participants in the community-based HTC studies had their CD4 count measured after HIV diagnosis, and 73% of the participants initiated antiretroviral therapy after their CD4 count fell below national eligibility criteria; both these observations suggest that community-based HTC successfully linked people to care. Finally, offering community-based HTC approaches in addition to facility-based approaches increased HTC coverage seven-fold at the population level.
What Do These Findings Mean?
These findings show that community-based HTC can achieve high HTC uptake rates and can reach HIV-positive individuals earlier, when they still have high CD4 counts. Importantly, they also suggest that the level of linkage to care of community-based HTC is similar to that of facility-based HTC. Although the lower positivity rate of community-based HTC approaches means that more people need to be tested with these approaches than with facility-based HTC to identify the same number of HIV-positive individuals, this downside of community-based HTC is likely to be offset by the earlier identification of HIV-positive individuals, which should improve life expectancy and reduce HIV transmission at the population level. Although further studies are needed to evaluate community-based HTC in other regions of the world, these findings suggest that offering community-based HTC in HIV programs in addition to facility-based testing should support the increased access to HIV prevention and care that is required for the intensification of HIV/AIDS elimination efforts.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001496.
The World Health Organization provides information on all aspects of HIV/AIDS, including information on counseling and testing (in several languages)
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 the global HIV/AIDS epidemic, on HIV testing, and on HIV transmission and testing (in English and Spanish)
The UK National Health Service Choices website provides information (including personal stories) about HIV and AIDS
The World AIDS Day Report 2012 provides up-to-date information about the AIDS epidemic and efforts to halt it
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 getting a diagnosis
doi:10.1371/journal.pmed.1001496
PMCID: PMC3742447  PMID: 23966838
18.  HIV/AIDS in Pakistan: the context and magnitude of an emerging threat 
STUDY OBJECTIVE: The objectives of this review were to: (1) assess the nature and comprehensiveness of information regarding HIV/AIDS in Pakistan; (2) to evaluate the extent of HIV/AIDS in Pakistan by epidemiological estimates; (3) to indicate the implications of the results for health policy in Pakistan and other regions at a similar stage in the epidemic. DESIGN: A structured review of published, unpublished, and government literature was undertaken to collate all available information and present a descriptive epidemiological profile of HIV/AIDS in the country. SETTING: Pakistan, a developing country in the South Asian region. National and regional information and analysis are presented in so far as the data allowed. Sample sizes varied from 1.35 million people screened at the national level to smaller studies of fewer than 100 screened. RESULTS: Data pertaining to HIV/AIDS in Pakistan showed the best national estimates of HIV prevalence as 64 per 100,000 (0.064%). Within patients with sexually transmitted diseases the seroprevalence was as high as 6100 per 100,000 (6.1%); in men with extramarital contacts, 5400 per 100,000 (5.4%) and was as low as zero in some studied populations as well. The average age of onset was reported as 30 years. It is estimated that if all incident cases of AIDS were to die, there would be at least 5000 deaths annually attributable to HIV/AIDS. CONCLUSION: Coupled with the extremely low awareness of HIV/AIDS in Pakistan, as well as growing number of cases, the AIDS epidemic is poised to take a hold in Pakistan. The presence of additional risk factors such as unscreened blood, and low condom use rates make the situation fertile for AIDS to become a major public health issue. Pakistan's health policy must be proactive in tackling this emerging health threat.
 
PMCID: PMC1756756  PMID: 10320859
19.  Uptake of Home-Based Voluntary HIV Testing in Sub-Saharan Africa: A Systematic Review and Meta-Analysis 
PLoS Medicine  2012;9(12):e1001351.
Kalpana Sabapathy and colleagues conduct a systematic review and meta-analysis to assess the acceptability of home-based voluntary counseling and testing for HIV in sub-Saharan Africa with some encouraging results.
Introduction
Improving access to HIV testing is a key priority in scaling up HIV treatment and prevention services. Home-based voluntary counselling and testing (HBT) as an approach to delivering wide-scale HIV testing is explored here.
Methods and Findings
We conducted a systematic review and random-effects meta-analysis of studies published between 1 January 2000 and 24 September 2012 that reported on uptake of HBT in sub-Saharan Africa, to assess the proportion of individuals accepting HBT and receiving their test result.
Our initial search yielded 1,199 articles; 114 were reviewed as full-text articles, and 19 publications involving 21 studies (n = 524,867 individuals offered HBT) were included for final review and meta-analysis. The studies came from five countries: Uganda, Malawi, Kenya, South Africa, and Zambia.
The proportion of people who accepted HBT (n = 474,377) ranged from 58.1% to 99.8%, with a pooled proportion of 83.3% (95% CI: 80.4%–86.1%). Heterogeneity was high (τ2 = 0.11). Sixteen studies reported on the number of people who received the result of HBT (n = 432,835). The proportion of individuals receiving their results out of all those offered testing ranged from 24.9% to 99.7%, with a pooled proportion of 76.7% (95% CI: 73.4%–80.0%) (τ2 = 0.12). HIV prevalence ranged from 2.9% to 36.5%. New diagnosis of HIV following HBT ranged from 40% to 79% of those testing positive. Forty-eight percent of the individuals offered testing were men, and they were just as likely to accept HBT as women (pooled odds ratio = 0.84; 95% CI: 0.56–1.26) (τ2 = 0.33). The proportion of individuals previously tested for HIV among those offered a test ranged from 5% to 66%. Studies in which <30% of individuals had been previously tested, local HIV prevalence was <10%, incentives were provided, or HBT was offered to household members of HIV-positive individuals showed higher uptake of testing. No evidence was reported of negative consequences of HBT.
Conclusions
HBT could substantially increase awareness of HIV status in previously undiagnosed individuals in sub-Saharan Africa, with over three-quarters of the studies in this review reporting >70% uptake. It could be a valuable tool for treatment and prevention efforts.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Knowledge of HIV status is crucial for both the prevention and treatment of HIV. However, according to the Joint United Nations Programme on HIV/AIDS (the UN agency responsible for HIV/AIDS), in low-and-middle-income countries only ten percent of those who need voluntary counseling and testing, because they may have been exposed to HIV infection, have access to this service. Even in health care settings in which voluntary counseling and HIV testing is routinely offered, such as to pregnant women, the number of people who use these services is low. This situation is partly because of the stigma and discrimination associated with HIV, which makes people reluctant to volunteer to come forward to be tested for HIV. To help overcome this problem, one important strategy in encouraging people to be tested for HIV is to offer them the opportunity to be counseled and tested at home—home-based voluntary counseling and testing (HBT). Using the HBT approach, people are visited in their home by health workers regardless of their perceived risk of HIV. HBT has obvious advantages and upholds the “3 Cs” principles of HIV testing: that testing is confidential, accompanied by counseling, and conducted only with informed consent.
Why Was This Study Done?
The HBT approach has received widespread international support, and the World Health Organization has recently published guidance to service providers and policy makers about the delivery of HBT. However, the acceptability of HBT, that is, whether those offered HBT actually take up the offer and are tested, remains unknown, especially in sub-Saharan Africa, the world region with the highest prevalence of HIV. So, in this study, the researchers systematically compiled all of the available studies on this topic from sub-Saharan Africa to determine the acceptability of HBT and also to and identify any factors associated with the uptake of HBT.
What Did the Researchers Do and Find?
The researchers searched several databases to identify suitable peer-reviewed studies from Africa published between January 2000 and September 2012. The researchers included studies that described any intervention to provide HIV testing at home and also reported the proportions of participants accepting HIV testing out of all individuals offered a home-based HIV test. Because different types of studies were included (such as randomized controlled trials, observational cohort studies, and cross-sectional surveys), the researchers tested the quality of included studies. Then they pooled all of the studies together to calculate the overall proportion of people who accepted HIV testing at home and the proportion who received their result.
Using these methods, the researchers included 21 studies from five African countries: Kenya, Malawi, South Africa, Uganda, and Zambia, comprising a total of 524,867 people. Overall, the proportion of people who accepted HBT ranged from 58.1% to 99.7%, with a pooled proportion of 83.3% accepting HBT (474,377 people). In the eight studies that separated data by gender, men were as likely as women to accept testing (78.5% versus 81.5%). Over three-quarters of everyone who accepted HBT received their result (77% in 16 studies reporting on this), and, importantly, the proportion of people with previously undiagnosed HIV was high (40%–79% of those diagnosed HIV-positive), emphasizing the value of HBT. The researchers also found that providing incentives, local HIV prevalence being less than 10%, and targeting HBT to household members of HIV-positive individuals may be factors associated with increased uptake of HBT, but further research is needed to verify the results of this subgroup analysis.
What Do These Findings Mean?
These findings suggest that voluntary counseling and testing for HIV at home is highly acceptable in five countries in sub-Saharan Africa, with the majority of those tested receiving their test result, highlighting the importance of this approach in the diagnosis of HIV. Therefore, by increasing uptake of testing, HBT may provide an effective tool for governments and health service providers to increase access to HIV treatment and prevention. However, testing is just the first step in the management of HIV, and this study does not address the follow-up of those who tested positive using the home-based approach, such as access to treatment, as well as repeated HBT for ongoing knowledge of HIV status. The option of self-testing was examined in only one of the studies included in this review, but the researchers identify that self-testing at home with the support HBT staff is an important area of future research. Overall, HBT has the potential to substantially increase awareness of HIV status in previously undiagnosed men and women in sub-Saharan Africa.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001351.
The World Health Organization provides extensive information on HIV testing and counseling, and the World Health Organization's guidance on home-based testing mentioned in this summary is also available
The Joint United Nations Programme on HIV/AIDS gives the latest facts and figures about the global status of HIV and about reducing stigma and discrimination around HIV
doi:10.1371/journal.pmed.1001351
PMCID: PMC3514284  PMID: 23226107
20.  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
21.  The Prevalence and Drug Sensitivity of Tuberculosis among Patients Dying in Hospital in KwaZulu-Natal, South Africa: A Postmortem Study 
PLoS Medicine  2010;7(6):e1000296.
A postmortem study by Ted Cohen and colleagues reveals a huge toll of tuberculosis among patients dying in hospitals in KwaZulu-Natal, South Africa.
Background
Tuberculosis is the leading cause of death in South Africa by death notification, but accurate diagnosis of tuberculosis is challenging in this setting of high HIV prevalence. We conducted limited autopsies on young adults dying in a single public hospital in the province of KwaZulu-Natal between October 2008 and August 2009 in order to estimate the magnitude of deaths attributable to tuberculosis.
Methods and Findings
We studied a representative sample of 240 adult inpatients (aged 20–45 years) dying after admission to Edendale Hospital. Limited autopsies included collection of respiratory tract secretions and tissue by needle core biopsies of lung, liver, and spleen. Specimens were examined by fluorescent microscopy for acid-fast bacilli and cultured in liquid media; cultures positive for M. tuberculosis were tested for drug susceptibility to first- and second-line antibiotics. Ninety-four percent of our study cohort was HIV seropositive and 50% of decedents had culture-positive tuberculosis at the time of death. Fifty percent of the participants were on treatment for tuberculosis at the time of death and 58% of these treated individuals remained culture positive at the time of death. Of the 50% not receiving tuberculosis treatment, 42% were culture positive. Seventeen percent of all positive cultures were resistant to both isoniazid and rifampin (i.e., multidrug resistant); 16% of patients dying during the initiation phase of their first ever course of tuberculosis treatment were infected with multidrug-resistant bacilli.
Conclusions
Our findings reveal the immense toll of tuberculosis among HIV-positive individuals in KwaZulu-Natal. The majority of decedents who remained culture positive despite receiving tuberculosis treatment were infected with pan-susceptible M. tuberculosis, suggesting that the diagnosis of tuberculosis was made too late to alter the fatal course of the infection. There is also a significant burden of undetected multidrug-resistant tuberculosis among HIV-coinfected individuals dying in this setting. New public health approaches that improve early diagnosis of tuberculosis and accelerate the initiation of treatment are urgently needed in this setting.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Every year, nearly 10 million people develop tuberculosis—a contagious bacterial infection that affects the lungs and other parts of the body—and nearly two million people die from the disease. Tuberculosis is caused by Mycobacterium tuberculosis, which spreads in airborne droplets when people with the disease cough or sneeze. Its characteristic symptoms are a persistent cough, weight loss, and night sweats. Diagnostic tests for tuberculosis include the microscopic examination of sputum samples (mucus brought up from the lungs by coughing) for M. tuberculosis bacilli, and mycobacterial culture (in which bacteriologists try to grow M. tuberculosis from sputum or tissue samples). Although tuberculosis can be cured by taking several powerful antibiotics regularly for at least 6 months, global efforts to control tuberculosis are being thwarted by the emergence of strains of M. tuberculosis that are resistant to several antibiotics (multidrug and extensively drug-resistant tuberculosis) and by the HIV epidemic; people who are infected with HIV, the virus that causes AIDS, are particularly susceptible to tuberculosis because of their weakened immune system.
Why Was This Study Done?
In the past few years, tuberculosis has become the leading recorded cause of death in South Africa, a country where nearly a fifth of adults are infected with HIV. There are 122,000 recorded deaths from tuberculosis (including 94,000 deaths in HIV-positive people) in South Africa every year. However, because the accurate diagnosis of tuberculosis in HIV-positive people can be difficult—they are more likely to have sputum-negative tuberculosis than HIV-negative individuals—the true number of people dying because of tuberculosis is likely to be higher than the recorded number. Public-health experts in South Africa need an accurate picture of the tuberculosis deaths to help them improve tuberculosis control. In this postmortem study, the researchers determine the prevalence (the proportion of a population that has a disease) and drug sensitivity of tuberculosis among patients dying in a public hospital in KwaZulu-Natal, South Africa, to get a better estimate of how many people die because of tuberculosis in this setting.
What Did the Researchers Do and Find?
The researchers collected respiratory tract secretions and lung, liver, and spleen samples from 240 adults who died in the Edendale public hospital in KwaZulu-Natal over a 10-month period in 2008/9. They looked for M. tuberculosis bacilli in the samples, tried to culture M. tuberculosis from them, and tested any bacteria that grew for antibiotic sensitivity. They also collected information on current tuberculosis treatment status, previous tuberculosis treatment, and HIV status for each deceased patient (decedent) from medical records and from relatives. Ninety-four percent of the decedents were HIV positive and 50% had culture-positive tuberculosis at the time of death. Of the 50% of the decedents who were being treated for tuberculosis, 58% were culture positive at the time of death. A similar percentage (42%) of the decedents who were not being treated for tuberculosis were culture positive at the time of death. Seventeen percent of all the positive cultures were multidrug resistant and 16% of patients dying during their first course of tuberculosis treatment were infected with multidrug-resistant bacteria. Seventy percent of decedents who remained culture positive despite receiving tuberculosis treatment were infected with M. tuberculosis strains that were susceptible to all antibiotics.
What Do These Findings Mean?
These findings reveal the immense toll of tuberculosis among HIV-infected individuals in this hospital in KwaZulu-Natal. They show that many patients being treated for tuberculosis were culture positive at death despite being infected with antibiotic-sensitive M. tuberculosis, which suggests that diagnoses of tuberculosis are often made too late to alter the fatal course of infection. These findings also suggest that multidrug-resistant tuberculosis often goes undetected among HIV-infected individuals. Further studies are needed to confirm these findings elsewhere in South Africa and in other countries with a high HIV prevalence. Nevertheless, they suggest that public-health initiatives that improve the early diagnosis of tuberculosis, that introduce routine screening for tuberculosis among HIV-positive patients, and that accelerate the initiation of treatment for both tuberculosis and HIV might reduce the global death toll from tuberculosis.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000296.
The World Health Organization provides information on all aspects of tuberculosis, including information on tuberculosis and HIV, on tuberculosis in South Africa, and on the Stop TB Partnership (some information is in several languages)
The US Centers for Disease Control and Prevention has information about tuberculosis and on tuberculosis and HIV coinfection
The US National Institute of Allergy and Infectious Diseases also has detailed information on all aspects of tuberculosis
Information is available from Avert, an international AIDS charity, on tuberculosis and HIV
doi:10.1371/journal.pmed.1000296
PMCID: PMC2889914  PMID: 20582324
22.  Undiagnosed Tuberculosis in a Community with High HIV Prevalence 
Background: Although failure of tuberculosis (TB) control in sub-Saharan Africa is attributed to the HIV epidemic, it is unclear why the directly observed therapy short-course (DOTS) strategy is insufficient in this setting. We conducted a cross-sectional survey of pulmonary TB (PTB) and HIV infection in a community of 13,000 with high HIV prevalence and high TB notification rate and a well-functioning DOTS TB control program.
Methods: Active case finding for PTB was performed in 762 adults using sputum microscopy and Mycobacterium tuberculosis culture, testing for HIV, and a symptom and risk factor questionnaire. Survey findings were correlated with notification data extracted from the TB treatment register.
Results: Of those surveyed, 174 (23%) tested HIV positive, 11 (7 HIV positive) were receiving TB therapy, 6 (5 HIV positive) had previously undiagnosed smear-positive PTB, and 6 (4 HIV positive) had smear-negative/culture-positive PTB. Symptoms were not a useful screen for PTB. Among HIV-positive and -negative individuals, prevalence of notified smear-positive PTB was 1,563/100,000 and 352/100,000, undiagnosed smear-positive PTB prevalence was 2,837/100,000 and 175/100,000, and case-finding proportions were 37 and 67%, respectively. Estimated duration of infectiousness was similar for HIV-positive and HIV-negative individuals. However, 87% of total person-years of undiagnosed smear-positive TB in the community were among HIV-infected individuals.
Conclusions: PTB was identified in 9% of HIV-infected individuals, with 5% being previously undiagnosed. Lack of symptoms suggestive of PTB may contribute to low case-finding rates. DOTS strategy based on passive case finding should be supplemented by active case finding targeting HIV-infected individuals.
doi:10.1164/rccm.200606-759OC
PMCID: PMC1899262  PMID: 16973982
African community; case finding; HIV infection; incidence and prevalence; pulmonary tuberculosis
23.  Epidemiology of Tuberculosis in a High HIV Prevalence Population Provided with Enhanced Diagnosis of Symptomatic Disease  
PLoS Medicine  2007;4(1):e22.
Background
Directly observed treatment short course (DOTS), the global control strategy aimed at controlling tuberculosis (TB) transmission through prompt diagnosis of symptomatic smear-positive disease, has failed to prevent rising tuberculosis incidence rates in Africa brought about by the HIV epidemic. However, rising incidence does not necessarily imply failure to control tuberculosis transmission, which is primarily driven by prevalent infectious disease. We investigated the epidemiology of prevalent and incident TB in a high HIV prevalence population provided with enhanced primary health care.
Methods and Findings
Twenty-two businesses in Harare, Zimbabwe, were provided with free smear- and culture-based investigation of TB symptoms through occupational clinics. Anonymised HIV tests were requested from all employees. After 2 y of follow-up for incident TB, a culture-based survey for undiagnosed prevalent TB was conducted. A total of 6,440 of 7,478 eligible employees participated. HIV prevalence was 19%. For HIV-positive and -negative participants, the incidence of culture-positive tuberculosis was 25.3 and 1.3 per 1,000 person-years, respectively (adjusted incidence rate ratio = 18.8; 95% confidence interval [CI] = 10.3 to 34.5: population attributable fraction = 78%), and point prevalence after 2 y was 5.7 and 2.6 per 1,000 population (adjusted odds ratio = 1.7; 95% CI = 0.5 to 6.8: population attributable fraction = 14%). Most patients with prevalent culture-positive TB had subclinical disease when first detected.
Conclusions
Strategies based on prompt investigation of TB symptoms, such as DOTS, may be an effective way of controlling prevalent TB in high HIV prevalence populations. This may translate into effective control of TB transmission despite high TB incidence rates and a period of subclinical infectiousness in some patients.
When occupational clinics provide free smear and culture-based investigation of tuberculosis symptoms, it can lead to prompt investigation and may aid TB control in high HIV-prevalence populations.
Editors' Summary
Background.
Around eight million people develop tuberculosis (TB) disease every year and of these nearly two million die. However, many more people are infected than have symptoms; perhaps one-third of the world's population is currently infected with TB. Most people infected with TB have what is termed “latent infection,” or in other words they are infected with the bacterium but do not experience any symptoms of disease. Individuals infected with TB who also have a weakened immune system, for example through HIV/AIDS, are much more likely to develop TB disease. In some regions HIV is very common—for example, approximately 11% of sub-Saharan African adults are HIV positive—and because of this cases of TB disease have risen substantially as HIV spreads. The Word Health Organization has a recommended international strategy for control of TB called “DOTS” (Directly Observed Therapy, Shortcourse). Among the five main elements of DOTS are mechanisms for promptly diagnosing and treating people who have TB disease. It is hoped that this strategy will help to reduce the number of new cases of TB diagnosed each year, because individuals promptly diagnosed and treated will then be less likely to transmit the disease to others.
Why Was This Study Done?
In this study the investigators wanted to find out if intensive DOTS, combined with giving people better access to test facilities to diagnose TB disease, could be effective in reducing the spread of TB from one person to another in Africa. It is not clear whether DOTS alone can control the spread of TB in populations with high numbers of HIV-positive people already infected with TB and so at high risk of going on to develop TB disease. Specifically, they wanted to collect data on the number of new TB cases being diagnosed per year and how that related to the proportion of the overall population that had infectious undiagnosed TB at any given point in time. They also wanted to find out whether providing good access to services for diagnosis and treatment of TB would affect either the number of new TB cases or the proportion of a given population that had infectious undiagnosed TB.
What Did the Researchers Do and Find?
This research study was carried out as part of a trial in which two different strategies for providing testing and counseling for HIV in the workplace were being compared. The trial took place within 22 companies in Harare, Zimbabwe, where HIV is very common in the adult population. Along with HIV testing and counseling, the trial provided for close follow-up and testing of anyone presenting with TB-like symptoms, with the aim of detecting as many cases in the population as possible. At the end of the two-year period, all workers were checked for undiagnosed TB disease, and cultures were carried out to find out how many of these people had infectious TB (but who might not necessarily have had symptoms). 6,440 workers were recruited into the study, of whom 19% were HIV positive. During the period of follow-up, 106 cases of TB were seen, and HIV-positive workers were far more likely than HIV-negative workers to experience TB disease. At the end of the study, 4,668 workers were checked for the presence of undiagnosed TB and 27 individuals were found to be affected, but not all of these people experienced any symptoms of disease.
What Do These Findings Mean?
At the end of this study, the proportion of workers found to have undiagnosed TB was fairly low—lower than the level found in other studies carried out in other parts of the world with a high burden of TB disease but low burden of HIV. The researchers therefore concluded that the systems set up within the trial (for close follow-up and testing for TB disease) were an effective way of controlling the overall proportion with infectious TB, even though HIV infection rates were also high. This is likely to mean that the spread of TB infection to others—a prerequisite for achieving TB disease control—was also well controlled. However, more intensive efforts to reduce the risk of TB disease in HIV-positive Africans already infected with TB are also needed, although this study did not aim to find out about the impact of such strategies.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0040022.
Information from the World Health Organization on DOTS, the internationally recommended TB control strategy; a factsheet on TB is also available
The STOP TB Partnership is an international initiative involving several agencies seeking to combat the rise of tuberculosis
The US National Institute of Allergy and Infectious Diseases also publishes a factsheet for patients
US Centers for Disease Control, information for patients and professionals about TB
doi:10.1371/journal.pmed.0040022
PMCID: PMC1761052  PMID: 17199408
24.  Impact of Round-the-Clock, Rapid Oral Fluid HIV Testing of Women in Labor in Rural India 
PLoS Medicine  2008;5(5):e92.
Background
Testing pregnant women for HIV at the time of labor and delivery is the last opportunity for prevention of mother-to-child HIV transmission (PMTCT) measures, particularly in settings where women do not receive adequate antenatal care. However, HIV testing and counseling of pregnant women in labor is a challenge, especially in resource-constrained settings. In India, many rural women present for delivery without any prior antenatal care. Those who do get antenatal care are not always tested for HIV, because of deficiencies in the provision of HIV testing and counseling services. In this context, we investigated the impact of introducing round-the-clock, rapid, point-of-care HIV testing and counseling in a busy labor ward at a tertiary care hospital in rural India.
Methods and Findings
After they provided written informed consent, women admitted to the labor ward of a rural teaching hospital in India were offered two rapid tests on oral fluid and finger-stick specimens (OraQuick Rapid HIV-1/HIV-2 tests, OraSure Technologies). Simultaneously, venous blood was drawn for conventional HIV ELISA testing. Western blot tests were performed for confirmatory testing if women were positive by both rapid tests and dual ELISA, or where test results were discordant. Round-the-clock (24 h, 7 d/wk) abbreviated prepartum and extended postpartum counseling sessions were offered as part of the testing strategy. HIV-positive women were administered PMTCT interventions. Of 1,252 eligible women (age range 18 y to 38 y) approached for consent over a 9 mo period in 2006, 1,222 (98%) accepted HIV testing in the labor ward. Of these, 1,003 (82%) women presented with either no reports or incomplete reports of prior HIV testing results at the time of admission to the labor ward. Of 1,222 women, 15 were diagnosed as HIV-positive (on the basis of two rapid tests, dual ELISA and Western blot), yielding a seroprevalence of 1.23% (95% confidence interval [CI] 0.61%–1.8%). Of the 15 HIV test–positive women, four (27%) had presented with reported HIV status, and 11 (73%) new cases of HIV infection were detected due to rapid testing in the labor room. Thus, 11 HIV-positive women received PMTCT interventions on account of round-the-clock rapid HIV testing and counseling in the labor room. While both OraQuick tests (oral and finger-stick) were 100% specific, one false-negative result was documented (with both oral fluid and finger-stick specimens). Of the 15 HIV-infected women who delivered, 13 infants were HIV seronegative at birth and at 1 and 4 mo after delivery; two HIV-positive infants died within a month of delivery.
Conclusions
In a busy rural labor ward setting in India, we demonstrated that it is feasible to introduce a program of round-the-clock rapid HIV testing, including prepartum and extended postpartum counseling sessions. Our data suggest that the availability of round-the-clock rapid HIV testing resulted in successful documentation of HIV serostatus in a large proportion (82%) of rural women who were unaware of their HIV status when admitted to the labor room. In addition, 11 (73%) of a total of 15 HIV-positive women received PMTCT interventions because of round-the-clock rapid testing in the labor ward. These findings are relevant for PMTCT programs in developing countries.
Nitika Pant Pai and colleagues report the results of offering a round-the-clock rapid HIV testing program in a rural labor ward setting in India.
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. Now, more than 33 million people are infected, almost half of them women. HIV is most often spread through unprotected sex with an infected partner, but mother-to-child transmission (MTCT) of HIV is also an important transmission route. HIV-positive women often pass the virus to their babies during pregnancy, labor and delivery, and breastfeeding, if nothing is done to prevent viral transmission. In developed countries, interventions such as voluntary testing and counseling, safe delivery practices (for example, offering cesarean delivery to HIV-positive women), and antiretroviral treatment of the mother during pregnancy and labor and of her newborn baby have minimized the risk of MTCT. In developing countries, the prevention of MTCT (PMTCT) is much less effective, in part because pregnant women often do not know their HIV status. Consequently, in 2007, nearly half a million children became infected with HIV mainly through MTCT.
Why Was This Study Done?
In many developing countries, women do not receive adequate antenatal care. In India, for example, nearly half the women living in rural areas do not receive any antenatal care until they are in labor. This gives health care providers very little time in which to counsel women about HIV infection, test them for the virus, and start interventions to prevent MTCT. Furthermore, testing pregnant women in labor for HIV and counseling them is a challenge, particularly where resources are limited. In this study, therefore, the researchers investigate the feasibility and impact of introducing round-the-clock, rapid HIV testing and counseling in a busy labor ward in a rural teaching hospital in Sevagram, India.
What Did the Researchers Do and Find?
Women admitted to the labor ward between January and September 2006 were offered two rapid HIV tests—one that used a saliva sample and the other that used blood taken from a finger prick. Blood was also taken from a vein for conventional HIV testing. All the women were given a 15-minute counseling session about how HIV is transmitted, the importance of HIV testing, and information on PMTCT before their child was born (prepartum counseling), and a longer postpartum counseling session. HIV-positive women were given a cesarean delivery where possible and antiretroviral drug treatment to reduce MTCT. 1,222 women admitted to the labor ward during the study period (1,003 of whom did not know their HIV status) accepted HIV testing. Of 15 study participants who were HIV positive, 11 learnt of their HIV status in the labor room. Two babies born to these HIV-positive women were HIV positive and died within a month of delivery; the other 13 babies were HIV negative at birth and at 1 and 4 months after delivery. Finally, the rapid HIV tests missed only one HIV-positive woman (no false-positive results were given), and the time from enrolling a woman into the study through referring her for PMTCT intervention where necessary averaged 40–60 minutes.
What Do These Findings Mean?
These findings show the feasibility and positive impact of the introduction of round-the-clock pre- and postpartum HIV counseling and rapid HIV testing into a busy rural Indian labor ward. Few of the women entering this ward knew their HIV status previously but the introduction of these facilities in this setting successfully informed these women of their HIV status. In addition, the round-the-clock counseling and testing led to 11 women and their babies receiving PMTCT interventions who would otherwise have been missed. These findings need to be confirmed in other settings and the cost-effectiveness and sustainability of this approach for the improvement of PMTCT in developing countries needs to be investigated. Nevertheless, these findings suggest that round-the-clock rapid HIV testing might be an effective and acceptable way to reduce MTCT of HIV in many developing countries.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0050092.
Read a related PLoS Medicine Perspective article
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 the 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 India, on women, HIV, and AIDS, and on HIV and AIDS prevention, including the prevention of mother-to-child transmission
AIDSinfo, a service of the US Department of Health and Human Services provides health information for HIV-positive pregnant women (in English and Spanish)
doi:10.1371/journal.pmed.0050092
PMCID: PMC2365974  PMID: 18462011
25.  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

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