Phase 1 Human Immunodeficiency Virus (HIV) Vaccine Trial to Evaluate the Safety and Immunogenicity of HIV Subtype C DNA and MF59-Adjuvanted Subtype C Envelope Protein.

BACKGROUND: The Pox-Protein Public-Private Partnership is performing a suite of trials to evaluate the bivalent subtype C envelope protein (TV1.C and 1086.C glycoprotein 120) vaccine in the context of different adjuvants and priming agents for human immunodeficiency virus (HIV) type 1 (HIV-1) prevention. METHODS: In the HIV Vaccine Trials Network 111 trial, we compared the safety and immunogenicity of DNA prime followed by DNA/protein boost with DNA/protein coadministration injected intramuscularly via either needle/syringe or a needle-free injection device (Biojector). One hundred thirty-two healthy, HIV-1-uninfected adults were enrolled from Zambia, South Africa, and Tanzania and were randomized to 1 of 6 arms: DNA prime, protein boost by needle/syringe; DNA and protein coadministration by needle/syringe; placebo by needle/syringe; DNA prime, protein boost with DNA given by Biojector; DNA and protein coadministration with DNA given by Biojector; and placebo by Biojector. RESULTS: All vaccinations were safe and well tolerated. DNA and protein coadministration was associated with increased HIV-1 V1/V2 antibody response rate, a known correlate of decreased HIV-1 infection risk. DNA administration by Biojector elicited significantly higher CD4+ T-cell response rates to HIV envelope protein than administration by needle/syringe in the prime/boost regimen (85.7% vs 55.6%; P = .02), but not in the coadministration regimen (43.3% vs 48.3%; P = .61). CONCLUSIONS: Both the prime/boost and coadministration regimens are safe and may be promising for advancement into efficacy trials depending on whether cellular or humoral responses are desired. CLINICAL TRIALS REGISTRATION: South African National Clinical Trials Registry (application 3947; Department of Health [DoH] no. DOH-27-0715-4917) and ClinicalTrials.gov (NCT02997969).

Temporal trends in sexual behaviours and their impacts on HIV incidence among South African women: 2002-2016.

South Africa has the highest number of HIV infected individuals in the world. The primary objective of the current study was to describe temporal changes in HIV incidence rates using the data from 9,948 women who enrolled in one of the six HIV prevention trials conducted in KwaZulu-Natal, South Africa. Characteristics of the study population were presented and compared across the four study periods: 2002-2004, 2005-2008, 2009-2011 and 2012-2016. HIV infection rates increased from 6.2 to 9.3 per 100 person-year over the 15 years. These rates were as high as 14 per 100 person-year among women younger than 20 years age. Being single/not cohabiting, using injectable contraceptives, having less than two children, and diagnosed with STI(s) were associated with increased risk of HIV infection. These four factors were associated with 71%, 75%, 80% and 88% of the HIV seroconversions in four study periods. As the research continues to find ways of controlling the spread of the infections, quantifying the temporal trends in risk factors and their population-level impacts on HIV infection may have significant implications. This information may assist in developing effective counselling and education programs by targeting the sexually active single women and delivering more realistic messages.

Quantifying Vulnerabilities of Single Women and Sexually Transmitted Infections in South Africa (2002-2016): Is It Getting Better (or Worse)?

Curable sexually transmitted infections (STIs) affect millions of people across the world. Besides unacceptably high HIV rates, South Africa also has the highest burden of STIs in the world. The aim of the study was to investigate temporal changes in STI incidence rates using the data from ~ 10,000 women who enrolled in several HIV prevention trials, KwaZulu-Natal, South Africa (2002-2016). We particularly focused on the changes in distribution of the most influential factors and their population-level impacts on STI incidence rates over time. Characteristics of the women were compared across the study periods: 2002-2004, 2005-2008, 2009-2011, and 2012-2016. Besides multivariable Cox regression models, population attributable risks were calculated for the significant factors. Despite the significant progress in prevention, testing, and treatment programs, infection rates increased substantially from 13.6 to 20.0 per 100 person-year over the study period. Our findings provided a compelling evidence for single/non-cohabiting South African women to be the most vulnerable population who consistently and substantially contributed to increasing STI rates during the 15 years of study duration (PAR%: 44%-47%). We also highlighted the impact of women's lack of knowledge related to their partner, using injectable contraceptives, less parity, and baseline STI positivity which were increased substantially over time. Our findings suggest that a significant proportion of STIs could be prevented by targeting single/non-cohabiting. These results may provide guidance in developing more effective STI prevention programs by targeting women at highest risk of infections and delivering more realistic messages.

Linkage to Care Following an HIV Diagnosis in Three Public Sector Clinics in eThekwini (Durban), South Africa: Findings from a Prospective Cohort Study.

Linkage to care following an HIV diagnosis remains an important HIV care continuum milestone, even in the era of universal ART eligibility. In an 8-month prospective cohort study among 459 (309 women, 150 men) newly-diagnosed HIV-positive individuals in three public-sector clinics in Durban metropolitan region, South Africa, from 2010 to 2013, median time to return to clinic for CD4+ results (linkage) was 10.71 weeks (95% CI 8.52-12.91), with 54.1% 3-month cumulative incidence of linkage. At study completion (9.23 months median follow-up), 26.2% had not linked. Holding more positive outcome-beliefs about enrolling in care was associated with more rapid linkage [adjusted hazard ratio (AHR)each additional belief 1.31; 95% CI 1.05-1.64] and lower odds of never linking [adjusted odds ratio (AOR) 0.50; 95% CI 0.33-0.75]. Holding positive ARV beliefs was strongly protective against never linking to care. Age over 30 years (AHR 1.59; 95% CI 1.29-1.97) and disclosing one's HIV-positive status within 30 days of diagnosis (AHR 1.52; 95% CI 1.10-2.10) were associated with higher linkage rates and lower odds of never linking. Gender was not associated with linkage and did not alter the effect of other predictors. Although expanded access to ART has reduced some linkage barriers, these findings demonstrate that people's beliefs and social relations also matter. In addition to structural interventions, consistent ART education and disclosure support, and targeting younger individuals for linkage are high priorities.

Correlates of Sexually Transmitted Infections Among South African Women Using Individual- and Community-Level Factors: Results from Generalized Additive Mixed Models.

South Africa has the highest burden of human immunodeficiency virus (HIV) infections in the world. There is also growing evidence that an individual's risk of contracting HIV is increased by the presence of other sexually transmitted infections (STIs). The primary objective of this study was to examine the association between the prevalence of STIs in a cohort of South African women who enrolled in HIV prevention trials (2002-2012). The current study linked the individual factors with the community-level characteristics using geo-referencing. These multi-level data were analyzed in generalized additive mixed models settings. In the multivariate logistic regression model, younger age (odds ratio [OR] 4.30, 95% CI 3.20, 5.77 and OR 2.72, 95% CI 2.02, 3.66 for age < 25 and 25-29, respectively); being single/not cohabiting (OR 4.57, 95% CI 3.18, 6.53), two + sex partners (OR 1.46, 95% CI 1.18,1.80); parity < 2 (OR 2.04, 95% CI 1.53, 2.72), parity = 2 (OR 1.85, 95% CI 1.37, 2.48), and using injectables (contraceptive) (OR 1.53, 95% CI 1.13, 2.06) were all significantly associated with increased prevalence of STIs. Women who resided in the communities with high proportions of female headed-households were also significantly at higher risk for STIs (OR 1.20, p = .0025). Because these factors may reflect characteristics of the larger groups who share similar cultural norms and social environments, they can provide considerable insight into the spread of STIs. Prevention strategies based on individual and community-level drivers of STIs are likely to be the most effective means of targeting and reaching those at greatest risk of infection. This strategy has the potential to play a significant role in the epidemic's trajectory.

Clinical and Virologic Outcomes Following Initiation of Antiretroviral Therapy Among Seroconverters in the Microbicide Trials Network-020 Phase III Trial of the Dapivirine Vaginal Ring.

BACKGROUND: A vaginal ring containing dapivirine, a non-nucleoside human immunodeficiency virus (HIV)-1 reverse transcriptase inhibitor (NNRTI), was safe and effective in preventing HIV-1 infection in African women. We examined the impact of dapivirine ring use at the time of HIV-1 acquisition on subsequent HIV-1 disease progression and responses to NNRTI-containing antiretroviral therapy (ART). METHODS: HIV-1 disease progression and virologic failure following initiation of ART were assessed among women who acquired HIV-1 while participating in Microbicide Trials Network-020, a randomized, placebo-controlled trial of a monthly, dapivirine vaginal ring. RESULTS: Among the 158 participants who acquired HIV-1 (65 dapivirine, 93 placebo), no differences between dapivirine and placebo participants were observed in CD4+ cell counts or plasma HIV-1 RNA over the first year after infection (prior to ART). During follow-up, 100/158 (63%) participants initiated NNRTI-containing ART (dapivirine: 39/65; placebo: 61/93); the median time to HIV-1 RNA <200 copies/ml was approximately 90 days for both dapivirine and placebo ring recipients (log-rank P = .40). Among the 81 participants with at least 6 months of post-ART follow-up, 19 (24%) experienced virologic failure (dapivirine: 6/32, 19%; placebo: 13/39, 27%; P = .42). CONCLUSIONS: The acquisition of HIV-1 infection during dapivirine or placebo treatment in ASPIRE did not lead to differences in HIV-1 disease progression. After the initiation of NNRTI-containing ART, dapivirine and placebo participants had similar times to virologic suppression and risks of virologic failure. These results provide reassurance that NNRTI-based ART regimens are effective among women who acquired HIV-1 while receiving the dapivirine vaginal ring. CLINICAL TRIALS REGISTRATION: NCT016170096 and NCT00514098.

Use of a Vaginal Ring Containing Dapivirine for HIV-1 Prevention in Women.

BACKGROUND: Antiretroviral medications that are used as prophylaxis can prevent acquisition of human immunodeficiency virus type 1 (HIV-1) infection. However, in clinical trials among African women, the incidence of HIV-1 infection was not reduced, probably because of low adherence. Longer-acting methods of drug delivery, such as vaginal rings, may simplify use of antiretroviral medications and provide HIV-1 protection. METHODS: We conducted a phase 3, randomized, double-blind, placebo-controlled trial of a monthly vaginal ring containing dapivirine, a non-nucleoside HIV-1 reverse-transcriptase inhibitor, involving women between the ages of 18 and 45 years in Malawi, South Africa, Uganda, and Zimbabwe. RESULTS: Among the 2629 women who were enrolled, 168 HIV-1 infections occurred: 71 in the dapivirine group and 97 in the placebo group (incidence, 3.3 and 4.5 per 100 person-years, respectively). The incidence of HIV-1 infection in the dapivirine group was lower by 27% (95% confidence interval [CI], 1 to 46; P=0.046) than that in the placebo group. In an analysis that excluded data from two sites that had reduced rates of retention and adherence, the incidence of HIV-1 infection in the dapivirine group was lower by 37% (95% CI, 12 to 56; P=0.007) than that in the placebo group. In a post hoc analysis, higher rates of HIV-1 protection were observed among women over the age of 21 years (56%; 95% CI, 31 to 71; P<0.001) but not among those 21 years of age or younger (-27%; 95% CI, -133 to 31; P=0.45), a difference that was correlated with reduced adherence. The rates of adverse medical events and antiretroviral resistance among women who acquired HIV-1 infection were similar in the two groups. CONCLUSIONS: A monthly vaginal ring containing dapivirine reduced the risk of HIV-1 infection among African women, with increased efficacy in subgroups with evidence of increased adherence. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT01617096 .).

Geographical-level contributions of risk factors for HIV infections using generalized additive models: results from a cohort of South African women.

South Africa has the highest burden of human immunodeficiency virus (HIV) infections in the world with significant geographical variations. We identified the predictors of HIV infections and their sub-geographical-level contributions to the epidemic using a decade long data (2002-2012) from 6484 South African women. Generalized additive models were used to uncover the most significant features of these estimates across the region. In the overall analysis, younger age, not married or cohabiting with a partner, partner has another partner(s) and null/prim parity, using injectable contraceptives and presence of other sexually transmitted infections (STIs) were identified as independent predictors of HIV seroconversions. Overall, the top three highest contributors to infections were women's marital status (PAR% = 73%, 95% CI: 68%, 77%), parity (PAR% = 47%, 95% CI: 42%, 53%) and partnership factors (PAR% = 37%, 95% CI: 30%, 44%). However, their contributions varied remarkably at sub-geographical level. This was mainly due to the substantial localized variations in their prevalence and hazard ratios across the region. Our results will guide policy makers to develop tailored prevention strategies in order to allocate scarce resources by targeting the most significant contributors of HIV infection at sub-geographical level.

A decade of sustained geographic spread of HIV infections among women in Durban, South Africa.

BACKGROUND: Fine scale geospatial analysis of HIV infection patterns can be used to facilitate geographically targeted interventions. Our objective was to use the geospatial technology to map age and time standardized HIV incidence rates over a period of 10 years to identify communities at high risk of HIV in the greater Durban area. METHODS: HIV incidence rates from 7557 South African women enrolled in five community-based HIV prevention trials (2002-2012) were mapped using participant household global positioning system (GPS) coordinates. Age and period standardized HIV incidence rates were calculated for 43 recruitment clusters across greater Durban. Bayesian conditional autoregressive areal spatial regression (CAR) was used to identify significant patterns and clustering of new HIV infections in recruitment communities. RESULTS: The total person-time in the cohort was 9093.93 years and 613 seroconversions were observed. The overall crude HIV incidence rate across all communities was 6·74 per 100PY (95% CI: 6·22-7·30). 95% of the clusters had HIV incidence rates greater than 3 per 100PY. The CAR analysis identified six communities with significantly high HIV incidence. Estimated relative risks for these clusters ranged from 1.34 to 1.70. Consistent with these results, age standardized HIV incidence rates were also highest in these clusters and estimated to be 10 or more per 100 PY. Compared to women 35+ years old younger women were more likely to reside in the highest incidence areas (aOR: 1·51, 95% CI: 1·06-2·15; aOR: 1.59, 95% CI: 1·19-2·14 and aOR: 1·62, 95% CI: 1·2-2·18 for < 20, 20-24, 25-29 years old respectively). Partnership factors (2+ sex partners and being unmarried/not cohabiting) were also more common in the highest incidence clusters (aOR 1.48, 95% CI: 1.25-1.75 and aOR 1.54, 95% CI: 1.28-1.84 respectively). CONCLUSION: Fine geospatial analysis showed a continuous, unrelenting, hyper HIV epidemic in most of the greater Durban region with six communities characterised by particularly high levels of HIV incidence. The results motivate for comprehensive community-based HIV prevention approaches including expanded access to PrEP. In addition, a higher concentration of HIV related services is required in the highest risk communities to effectively reach the most vulnerable populations.

Association of endogenous progesterone levels in young women using hormonal contraception with recent HIV-1 infection.

BACKGROUND: A high endogenous progesterone luteal state in the menstrual cycle has been independently associated with Human Immunodeficiency Virus (HIV) incidence in epidemiological studies. Hormonal contraception particularly high dose Depot Medroxyprogesterone Acetate (DMPA) is also thought to increase the risk of HIV acquisition. Inconsistent reports of this association have led us to hypothesize that unsuppressed endogenous progesterone level in women who reported hormonal contraception (HC) use may be an explanation for increased vulnerability to HIV. METHODS: This pilot study was a secondary cross-sectional analysis of data and laboratory testing of stored specimens collected from women who participated in the SAMRC HIV prevention MDP 301 trial during 2005-2009 in South Africa. Serum progesterone levels were measured in 39 women at the point of first positive HIV diagnosis during study follow-up and 36 women who remained HIV uninfected at the 52-week study exit visit. RESULTS: Overall, the median (IQR) progesterone level in 49 women using hormonal contraception was 0.39 ng/ml (IQR 0.13-0.45) and 48 (97.9%) women had a progesterone level < 3.0 ng/ml suggestive of adequate progesterone suppression for contraceptive efficacy. After excluding the one woman with a progesterone level of > 3.0 ng/ml, the median progesterone level in women using DMPA remained marginally higher at 0.42 ng/ml (IQR 0.27-0.45) than women using Norethisterone Enanthate (NET-EN) (0.31 ng/ml; IQR 0.13-0.41, p = 0.061). For women using hormonal contraception, the median progesterone level did not differ between women with recent HIV infection or women who remained HIV negative (0.39 vs 0.38 ng/ml, p = 0.959). Similarly, the median progesterone level in women using DMPA or NET-EN did not differ by HIV status (0.43 vs 0.41 ng/ml, p = 0.905; 0.24 vs 0.31 ng/ml, p = 0.889). CONCLUSION: Among women using hormonal contraception, DMPA or NET-EN we did not observe a significant difference in progesterone levels between women with recently acquired HIV infection and women who remained HIV negative. Our findings suggest that endogenous progesterone levels remain suppressed in the presence of hormonal contraception and are not likely to be associated with HIV acquisition.

Point-of-care HIV testing best practice for early infant diagnosis: an implementation study.

BACKGROUND: With Universal Health Coverage and Integrated People-centred Health Care, streamlined health-systems and respectful care are necessary. South Africa has made great strides in prevention of mother-to-child transmission (PMTCT) but with the great burden of HIV, a minimum of birth and 10-week HIV-PCR testing are required for the estimated 360,000 HIV-exposed infants born annually which presents many challenges including delayed results and loss to follow-up. Point-of-care (POC) HIV testing of infants addresses these challenges well and facilitates initiation of HIV-infected infants rapidly after diagnosis for best clinical outcomes. METHODS: Objectives were to determine accuracy, feasibility and acceptability of POC testing compared to standard-of-care (SOC) central-laboratory testing. HIV-exposed infants for birth PCR testing in hospital (n = 323) and follow-up at a primary health care clinic (n = 117) in Durban, South Africa were included. A baseline situational-analysis reviewed registers and phoned mothers of HIV-exposed infants prior to the intervention. An effectiveness-implementation study of the Alere™q HIV-1/2 Detect POC test (heel-prick specimen processed in 50 min) was compared with SOC with questionnaires to mothers and staff. Stata 14 was used for analysis. RESULTS: At baseline 2% of birth HIV tests were missed; only 40% of mothers could be contacted; 17% did not receive birth test result; 19% did not have a 10-week test; 39% had not received the 10-week results. There were 5(1.5%) HIV-infected and 318(98.5%) HIV-negative infants detected in hospital with all clinic babies negative. All positive infants commenced ART before discharge. Ultimately POC and SOC had perfect concordance but for 10 SOC tests researchers actively tracked-down results or repeated tests. Turn around times for SOC tests were on average 8-days (IQR 6-10 days) and for POC testing was 0-days. The POC error-rate was 9,6% with all giving a result when repeated. The majority of mothers (92%) preferred POC testing with 7% having no preference. No staff preferred SOC testing with 79% preferring POC and 21% having no preference. CONCLUSIONS: Point-of-care HIV testing for EID is accurate, feasible and acceptable, with benefits of early ART for all positive infants at birth facilities. We recommend that it be considered best practice for EID. TRIAL REGISTRATION: ISRCTN38911104 registered 9 January 2018 - retrospectively registered.

Targeted Pregnancy and Human Immunodeficiency Virus Prevention Risk-Reduction Counseling for Young Women: Lessons Learned from Biomedical Prevention Trials.

Background: Women enrolled in human immunodeficiency virus (HIV) prevention efficacy trials receive counseling on prevention of HIV, sexually transmitted infections (STIs), and pregnancy during every visit. Incident pregnancy has an impact on efficacy outcomes. Incidence rates of pregnancy and HIV/STIs among women who became pregnant and associated risk factors were assessed. Methods: Data from 9165 women participating in HIV prevention trials in KwaZulu-Natal, South Africa from 2002-2012 were combined. Demographic and behavioral predictors of incidence pregnancy and incidence HIV and STIs were determined using Cox regression models. Results: Overall pregnancy incidence was 9.6 per 100 person-year (py) (95% confidence interval [Cl], 9.1-10.3). Human immunodeficiency virus incidence among pregnant women was 5.93 per 100 py (95% Cl, 4.73-7.44). Incidence of STIs among pregnant women for Chlamydia trachomatis, Trichomonas vaginalis, Neisseria gonorrhoeae, and Treponema pallidum (syphilis) were 10.87, 7.42, 3.92, and 1.43 per 100 py, respectively. In the adjusted analyses, we observed overlapping risk factors for HIV acquisition during pregnancy, ie, young age, not married/not cohabitating, and low parity. The risk of pregnancy and HIV acquisition is more than 3 times higher among young women (<20 years of age). Conclusions: We identified overlapping risk factors for pregnancy and HIV incidence, suggesting an urgent need for appropriate, targeted, individual-centred counseling for women participating in HIV prevention trials.

Tenofovir-based preexposure prophylaxis for HIV infection among African women.

BACKGROUND: Reproductive-age women need effective interventions to prevent the acquisition of human immunodeficiency virus type 1 (HIV-1) infection. METHODS: We conducted a randomized, placebo-controlled trial to assess daily treatment with oral tenofovir disoproxil fumarate (TDF), oral tenofovir-emtricitabine (TDF-FTC), or 1% tenofovir (TFV) vaginal gel as preexposure prophylaxis against HIV-1 infection in women in South Africa, Uganda, and Zimbabwe. HIV-1 testing was performed monthly, and plasma TFV levels were assessed quarterly. RESULTS: Of 12,320 women who were screened, 5029 were enrolled in the study. The rate of retention in the study was 91% during 5509 person-years of follow-up. A total of 312 HIV-1 infections occurred; the incidence of HIV-1 infection was 5.7 per 100 person-years. In the modified intention-to-treat analysis, the effectiveness was -49.0% with TDF (hazard ratio for infection, 1.49; 95% confidence interval [CI], 0.97 to 2.29), -4.4% with TDF-FTC (hazard ratio, 1.04; 95% CI, 0.73 to 1.49), and 14.5% with TFV gel (hazard ratio, 0.85; 95% CI, 0.61 to 1.21). In a random sample, TFV was detected in 30%, 29%, and 25% of available plasma samples from participants randomly assigned to receive TDF, TDF-FTC, and TFV gel, respectively. Independent predictors of TFV detection included being married, being older than 25 years of age, and being multiparous. Detection of TFV in plasma was negatively associated with characteristics predictive of HIV-1 acquisition. Elevations of serum creatinine levels were seen more frequently among participants randomly assigned to receive oral TDF-FTC than among those assigned to receive oral placebo (1.3% vs. 0.2%, P=0.004). We observed no significant differences in the frequencies of other adverse events. CONCLUSIONS: None of the drug regimens we evaluated reduced the rates of HIV-1 acquisition in an intention-to-treat analysis. Adherence to study drugs was low. (Funded by the National Institutes of Health; VOICE ClinicalTrials.gov number, NCT00705679.).

Prevalent Herpes Simplex Virus-2 Increases the Risk of Incident Bacterial Vaginosis in Women from South Africa.

Studies have shown that women diagnosed with herpes simplex virus-2 (HSV-2) have a higher risk for bacterial vaginosis (BV) infection. We investigated the presence of HSV-2 infections as a risk factor for incident BV infections in high risk, Human immunodeficiency virus (HIV) uninfected women enrolled in a HIV prevention trial in Durban, South Africa. The Vaginal and Oral Interventions to Control the Epidemic trial was a multicentre, double blinded, randomized controlled trial which was designed to estimate the effectiveness of daily treatment with vaginal tenofovir gel, oral tenofovir disoproxil fumarate and oral Truvada in preventing HIV-1 infection in women. Women provided samples for the diagnosis of HSV-2 and BV. The presence of HSV-2 antibodies was detected using HerpeSelect™ ELISA IgG. Bacterial vaginosis was diagnosed using the Nugent scoring system. To assess the risk of BV incidence, modelled as a time-dependent variable, we used the Andersen-Gill model with robust variance estimation and Efron methods for ties. Overall, 2750 women were enrolled in the VOICE trial at our study sites. Women who had a HSV-2 infection at enrolment were shown to be at increased risk for incident BV infections (adjusted hazard ratio 1.17, 95% CI 1.08, 1.27, p ≤ 0.001). In addition, being of a young age, being unmarried and having a partner that has other partners were significantly associated with subsequent BV infection. Our findings therefore advocate the need for strengthening STI prevention efforts among women in high burden STI settings.

A Simple Risk Prediction Algorithm for HIV Transmission: Results from HIV Prevention Trials in KwaZulu Natal, South Africa (2002-2012).

We aimed to develop a HIV risk scoring algorithm for targeted screening among women in South Africa. We used data from five biomedical intervention trials (N = 8982 Cox regression models were used to create a risk prediction algorithm and it was internally and externally validated using standard statistical measures; 7-factors were identified as significant predictors of HIV infection: <25 years old, being single/not cohabiting, parity (<3), age at sexual debut (<16), 3+ sexual partners, using injectables and diagnosis with a sexually transmitted infection(s). A score of ≥25 (out of 50) was the optimum cut point with 83% (80%) sensitivity in the development (validation) dataset. Our tool can be used in designing future HIV prevention research and guiding recruitment strategies as well as in health care settings. Identifying, targeting and prioritising women at highest risk will have significant impact on preventing new HIV infections by scaling up testing and pre-exposure prophylaxis in conjunction with other HIV prevention modalities.

Social Support and Violence-prone Relationships as Predictors of Disclosure of HIV Status Among Newly Diagnosed HIV-positive South Africans.

Despite the salience of social support and violence as potential outcomes of disclosure, how pre-existing social support and relationship violence among people living with HIV shapes and influences HIV status disclosure has received limited attention. Following the Disclosure Process Model, this study investigated pre-disclosure support and violence-prone relationships as predictors of disclosure using data from a prospective study of 459 newly diagnosed South African women and men. Most (88%) disclosed their status to at least one person by their 8-month interview. Level of social support was unrelated to disclosure to a partner. However, those with higher levels of support had higher odds of disclosing to family and to others. Women in violence-prone relationships were more likely to report disclosure to a partner than were those not in such relationships, counter to expectations. The findings suggest that the same mechanisms may not explain processes of disclosure across all relationship types.

"I did not see a need to get tested before, everything was going well with my health": a qualitative study of HIV-testing decision-making in KwaZulu-Natal, South Africa.

Few studies have examined HIV-testing decision-making since the South African national HIV counseling and testing campaign in 2010-2011 and subsequent expansion in antiretroviral therapy (ART) eligibility in 2012. We describe HIV-testing decision-making and pathways to testing among participants in Pathways to Care, a cohort study of newly-diagnosed HIV-positive adults in KwaZulu-Natal. Our analysis is embedded within a theoretical framework informed by Arthur Kleinman's work on pluralistic healthcare systems, and the concept of diagnostic itineraries (i.e., the route taken to HIV testing). We conducted 26 semi-structured interviews in 2012, within one month of participants' diagnosis. Most (n = 22) deferred testing until they had developed symptoms, and then often sought recourse in non-biomedical settings. Of the eleven symptomatic participants who accessed professional medical services prior to testing, only three reported that a healthcare professional had offered or recommended an HIV test. Although ART emerged as an important motivator, offering hope of health and normalcy, fear of death and HIV-related stigma remained key barriers. Despite national policy changes in testing and treatment, health system and individual factors contributed to ongoing high levels of late diagnosis of HIV in this study population. Encouraging local health systems to direct clients toward HIV testing, and continuing to raise awareness of the benefits of routine testing remain important strategies to reduce delayed diagnoses.

Identifying Factors Associated with Low-Adherence and Subsequent HIV Seroconversions Among South African Women Enrolled in a Biomedical Intervention Trial.

Sub-Saharan Africa has the highest number of HIV infected individuals in the world. Developing and implementing effective biomedical interventions still remains urgent. Poor adherence has been commonly identified as one of the major barriers for the success of HIV prevention trials. A better understanding of how to improve adherence remains a research priority. In this analysis, younger age (<35 years), number of children ≤2, being single/not cohabiting and having a new partner during the study follow up were all significantly associated with poor adherence and subsequent HIV seroconversions. At population level, these three factors collectively associated with 56 % of the low level adherence and 75 % of the HIV seroconversions. Results highlighted the importance of effective adherence and comprehensive contraceptive counselling of women who enrol in HIV prevention trials. Culturally and socially appropriate methods are needed to achieve and maintain optimum adherence levels in future HIV prevention research.

Short-course antiretroviral therapy in primary HIV infection.

BACKGROUND: Short-course antiretroviral therapy (ART) in primary human immunodeficiency virus (HIV) infection may delay disease progression but has not been adequately evaluated. METHODS: We randomly assigned adults with primary HIV infection to ART for 48 weeks, ART for 12 weeks, or no ART (standard of care), with treatment initiated within 6 months after seroconversion. The primary end point was a CD4+ count of less than 350 cells per cubic millimeter or long-term ART initiation. RESULTS: A total of 366 participants (60% men) underwent randomization to 48-week ART (123 participants), 12-week ART (120), or standard care (123), with an average follow-up of 4.2 years. The primary end point was reached in 50% of the 48-week ART group, as compared with 61% in each of the 12-week ART and standard-care groups. The average hazard ratio was 0.63 (95% confidence interval [CI], 0.45 to 0.90; P=0.01) for 48-week ART as compared with standard care and was 0.93 (95% CI, 0.67 to 1.29; P=0.67) for 12-week ART as compared with standard care. The proportion of participants who had a CD4+ count of less than 350 cells per cubic millimeter was 28% in the 48-week ART group, 40% in the 12-week group, and 40% in the standard-care group. Corresponding values for long-term ART initiation were 22%, 21%, and 22%. The median time to the primary end point was 65 weeks (95% CI, 17 to 114) longer with 48-week ART than with standard care. Post hoc analysis identified a trend toward a greater interval between ART initiation and the primary end point the closer that ART was initiated to estimated seroconversion (P=0.09), and 48-week ART conferred a reduction in the HIV RNA level of 0.44 log(10) copies per milliliter (95% CI, 0.25 to 0.64) 36 weeks after the completion of short-course therapy. There were no significant between-group differences in the incidence of the acquired immunodeficiency syndrome, death, or serious adverse events. CONCLUSIONS: A 48-week course of ART in patients with primary HIV infection delayed disease progression, although not significantly longer than the duration of the treatment. There was no evidence of adverse effects of ART interruption on the clinical outcome. (Funded by the Wellcome Trust; SPARTAC Controlled-Trials.com number, ISRCTN76742797, and EudraCT number, 2004-000446-20.).

Sharing of Investigational Drug Among Participants in the Voice Trial.

Product sharing among participants can impact on adherence and compromise the outcome in clinical trials. We describe incidents of product sharing at the Durban clinical research sites conducting the VOICE trial. The Durban sites enrolled 2750 women with 1103 and 1647 participants randomized to the vaginal gel and oral tablet arms respectively. Monthly pill and applicator counts including product assessments were conducted by pharmacists. Discrepancies with product counts prompted discussions with participants. Thirty-two cases of product sharing were identified. Vaginal gels were more commonly shared than oral tablets. Product sharing between study participants and their female friends or relatives living in the same household was identified as the most common source of product sharing in this analysis. Study product counts and pharmacist-driven discussions with participants may help to identify reasons for product sharing and inform the development of strategies for PrEP implementation outside of the research setting. ClinicalTrials.gov number: NCT00705679.