Omicron infection enhances Delta antibody immunity in vaccinated persons.

The extent to which Omicron infection1-9, with or without previous vaccination, elicits protection against the previously dominant Delta (B.1.617.2) variant is unclear. Here we measured the neutralization capacity against variants of severe acute respiratory syndrome coronavirus 2 in 39 individuals in South Africa infected with the Omicron sublineage BA.1 starting at a median of 6 (interquartile range 3-9) days post symptom onset and continuing until last follow-up sample available, a median of 23 (interquartile range 19-27) days post symptoms to allow BA.1-elicited neutralizing immunity time to develop. Fifteen participants were vaccinated with Pfizer's BNT162b2 or Johnson & Johnson's Ad26.CoV2.S and had BA.1 breakthrough infections, and 24 were unvaccinated. BA.1 neutralization increased from a geometric mean 50% focus reduction neutralization test titre of 42 at enrolment to 575 at the last follow-up time point (13.6-fold) in vaccinated participants and from 46 to 272 (6.0-fold) in unvaccinated participants. Delta virus neutralization also increased, from 192 to 1,091 (5.7-fold) in vaccinated participants and from 28 to 91 (3.0-fold) in unvaccinated participants. At the last time point, unvaccinated individuals infected with BA.1 had low absolute levels of neutralization for the non-BA.1 viruses and 2.2-fold lower BA.1 neutralization, 12.0-fold lower Delta neutralization, 9.6-fold lower Beta variant neutralization, 17.9-fold lower ancestral virus neutralization and 4.8-fold lower Omicron sublineage BA.2 neutralization relative to vaccinated individuals infected with BA.1. These results indicate that hybrid immunity formed by vaccination and Omicron BA.1 infection should be protective against Delta and other variants. By contrast, infection with Omicron BA.1 alone offers limited cross-protection despite moderate enhancement.

Host genetic variation at a locus near CHD1L impacts HIV sequence diversity in a South African population.

IMPORTANCE: It has been previously shown that genetic variants near CHD1L on chromosome 1 are associated with reduced HIV VL in African populations. However, the impact of these variants on viral diversity and how they restrict viral replication are unknown. We report on a regional association analysis in a South African population and show evidence of selective pressure by variants near CHD1L on HIV RT and gag. Our findings provide further insight into how genetic variability at this locus contributes to host control of HIV in a South African population.

Exposure to comprehensive sexuality education in schools in South Africa: the implications on the uptake of HIV testing services among HIV positive adolescent girls.

Comprehensive sexuality education (CSE) is seen as a key instrument through which to affect behaviour and improve sexual and reproductive health (SRH) outcomes amongst adolescents. However, few studies have to date evaluated key SRH outcomes following exposure to CSE within a school setting. This study estimates the association between CSE and HIV testing and HIV testing self-efficacy amongst HIV positive adolescent girls. Data were collected from a cross-sectional survey administered in four high HIV prevalence districts . Independent variables included exposure to CSE, with outcome variables measuring uptake of HIV testing in the 12 months preceding the survey, and HIV testing self-efficacy. The sample comprised 505 HIV positive adolescent girls aged 12-19. . Attending CSE was associated with both; being more confident to get an HIV test (AOR: 2.44, 95% CI: 1.47-4.06, p < 0.001) and having ever tested for HIV (AOR: 2.15, 95% CI: 1.39-3.33, p < 0.001) while controlling for numerous variables. Results suggest CSE can play an important role in not only affecting HIV-related behaviours themselves, but also critical factors that affect HIV behaviours, including self-efficacy.

Associations of Social Support with Sexual Practices, Health Behaviours, and Health Outcomes Among Adolescent Girls and Young Women: Evidence From a Longitudinal Study in KwaZulu-Natal, South Africa.

BACKGROUND: Several studies have reported on the benefits of social support for health behaviour, including risky sex. Social support may thus be an important resource for promoting individual health and well-being, particularly in regions where HIV rates are high and healthcare resources are scarce. However, prior research on the implications of social support for the health behaviour of young women has yielded mixed and inconclusive findings. Using prospective data from young women in South Africa, this study examines the associations of social support with subsequent sexual practices, health behaviour, and health outcomes. METHOD: We used two rounds of longitudinal data from a sample of n = 1446 HIV-negative emerging adult women, aged 18 to 29 years, who participated in a population-based HIV study in KwaZulu-Natal, South Africa. Applying the analytic template for outcome-wide longitudinal designs, we estimated the associations between combinations of social support (i.e. tangible, educational, emotional) and ten HIV risk-related outcomes. RESULTS: Combinations of tangible, educational, and emotional support, as well as tangible support by itself, were associated with lower risk for several outcomes, whereas educational and emotional support, by themselves or together, showed little evidence of association with the outcomes. CONCLUSION: This study highlights the protective role of tangible support in an environment of widespread poverty, and the additional effect of combining tangible support with non-tangible support. The findings strengthen recent evidence on the benefits of combining support in the form of cash and food with psychosocial care in mitigating risk behaviours associated with HIV and negative health outcomes among young women.

Clinical Evaluation of Severe Acute Respiratory Syndrome Coronavirus 2 Rapid Antigen Tests During the Omicron Wave in South Africa.

We evaluated the performance of nasal and nasopharyngeal Standard Q COVID-19 [coronavirus disease 2019] Ag tests (SD Biosensor) and the Panbio COVID-19 Ag Rapid Test Device (nasal; Abbott) against the Abbott RealTime severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) assay during the Omicron (clades 21M, 21K, and 21L) wave in South Africa. Overall, all evaluated tests performed well, with high sensitivity (range, 77.78%-81.42%) and excellent specificity values (>99%). The sensitivity of rapid antigen tests increased above 90% in samples with cycle threshold <20, and all 3 tests performed best within the first week after symptom onset.

Identifying Potential Factors Associated with High HIV viral load in KwaZulu-Natal, South Africa using Multiple Correspondence Analysis and Random Forest Analysis.

BACKGROUND: Sustainable Human Immunodeficiency Virus (HIV) virological suppression is crucial to achieving the Joint United Nations Programme of HIV/AIDS (UNAIDS) 95-95-95 treatment targets to reduce the risk of onward HIV transmission. Exploratory data analysis is an integral part of statistical analysis which aids variable selection from complex survey data for further confirmatory analysis. METHODS: In this study, we divulge participants' epidemiological and biological factors with high HIV RNA viral load (HHVL) from an HIV Incidence Provincial Surveillance System (HIPSS) sequential cross-sectional survey between 2014 and 2015 KwaZulu-Natal, South Africa. Using multiple correspondence analysis (MCA) and random forest analysis (RFA), we analyzed the linkage between socio-demographic, behavioral, psycho-social, and biological factors associated with HHVL, defined as ≥400 copies per m/L. RESULTS: Out of 3956 in 2014 and 3868 in 2015, 50.1% and 41% of participants, respectively, had HHVL. MCA and RFA revealed that knowledge of HIV status, ART use, ARV dosage, current CD4 cell count, perceived risk of contracting HIV, number of lifetime HIV tests, number of lifetime sex partners, and ever diagnosed with TB were consistent potential factors identified to be associated with high HIV viral load in the 2014 and 2015 surveys. Based on MCA findings, diverse categories of variables identified with HHVL were, did not know HIV status, not on ART, on multiple dosages of ARV, with less likely perceived risk of contracting HIV and having two or more lifetime sexual partners. CONCLUSION: The high proportion of individuals with HHVL suggests that the UNAIDS 95-95-95 goal of HIV viral suppression is less likely to be achieved. Based on performance and visualization evaluation, MCA was selected as the best and essential exploration tool for identifying and understanding categorical variables' significant associations and interactions to enhance individual epidemiological understanding of high HIV viral load. When faced with complex survey data and challenges of variables selection in research, exploratory data analysis with robust graphical visualization and reliability that can reveal divers' structures should be considered.

Pregnancy rates and outcomes in a longitudinal HIV cohort in the context of evolving antiretroviral treatment provision in South Africa.

BACKGROUND: In South Africa, women continue to face a high burden of Human Immunodeficiency Virus (HIV) infection and the possible complications thereof during pregnancy. We assessed pregnancy incidence rates and outcomes in a longitudinal HIV cohort study over a 15-year period. METHODS: We evaluated pregnancies among women ≥ 18 years between 2004 and 2019 in the CAPRISA 002 study. We analysed pregnancy rates following HIV acquisition, CD4 counts and HIV viral load dynamics and pregnancy outcomes. We used linear regression to assess if the mean CD4 and log10 viral load close to delivery increases or decreases linearly across three different timepoints. RESULTS: In total 245 women enrolled into the HIV negative study phase, 225 into the HIV infection phase and 232 in the antiretroviral therapy (ART) phase. Median follow-up time was 2.0 years [Interquartile Range (IQR) 0.8-2.0] during the HIV negative phase, 2.6 years; (IQR) 1.2-4.8] during HIV infection and 3.7 years (IQR 1.8-5.0) on ART, with maximum follow-up time of 2, 10 and 6 years respectively. Overall, 169 pregnancies occurred in 140 women, of which 16 pregnancies were observed during acute or early HIV infection [Incidence Rate (IR) 8.0 per 100 women-years; 95% confidence interval (CI): 4.6-12.9], 48 during established infection [IR 9.3; (CI 6.8-12.3)] and 68 on ART [IR 8.9; (CI: 7.0 - 11.4)]. Birth outcomes from 155/169 (91.7%) pregnancies were 118 (76.1%) full term live births, 17 (10.9%) premature live births, 9 (5.8%) therapeutic/elective miscarriages, 8 (5.1%) spontaneous miscarriages and 3 (1.9%) spontaneous foetal deaths or stillbirths. Six mother-to-child transmission events occurred, with four documented prior to 2008. Over time, mean CD4 count in pregnant women increased from 395 cells/µL (2004-2009) to 543 cells/µL (2010-2014) and to 696 cells/µL (2015-2019), p < 0.001. Conversely, the viral load declined from 4.2 log10 copies/ml to 2.5 log10 copies/ml and to 1.2 log10 copies/ml (p < 0.001) for the corresponding periods. CONCLUSIONS: Pregnancy rates following HIV acquisition were high, emphasising a need for timeous ART provision and contraception counselling in women recently diagnosed with HIV. CD4 count and HIV viral load trajectories reflect improvements in treatment guidance for pregnant women over time.

Determining HIV risk for Adolescent Girls and Young Women (AGYW) in relationships with "Blessers" and age-disparate partners: a cross-sectional survey in four districts in South Africa.

BACKGROUND: HIV incidence among adolescent girls and young women (AGYW) remains high, with their male partners a prominent factor in sustaining these elevated rates. Partnership characteristics remain important metrics for determining HIV risk, with evidence indicating that AGYW engaged in transactional and age-disparate relationships face greater HIV exposure. This study examines the risk posed to AGYW in a relationship with a "Blesser", defined as male who provides his female partner with their material needs or desires in exchange for a sexual relationship, an age-disparate (5 or more years older) partner, and the potential compounded risk of being a relationship with a partner or partners who are considered both a "Blesser" and age-disparate. METHODS: A cross -sectional household based representative sample of AGYW (aged between 12-24 years) were enrolled in the study (n = 18 926) from the districts of City of Johannesburg and Ekurhuleni in the Gauteng province and the Districts of eThekwini and uMgungundlovu in the province of KwaZulu-Natal (KZN) in South Africa between March 13, 2017 to June 22, 2018. Participants completed a structured questionnaire and provided finger-prick blood samples for laboratory measurements. Our analysis used descriptive statistics and multiple binary logistic regressions accounting for survey weights, clustering and stratification. FINDINGS: The median age of the sample was 21 years old (Interquartile range: 19-23) and nearly three quarters (73.7%) were currently attending school. Whilst all relationships exposed AGYW to potential HIV risk, multiple binary logistic regression analysis revealed that AGYW in a relationship with both a Blesser and an age-disparate partner were more likely to be HIV positive (AOR: 3.12, 95% CI: 1.76-5.53, p < 0.001), diagnosed with an STI (AOR: 4.60, 95% CI: 2.99-7.08, p < 0.001), had 2 or more sexual partners in the previous 12 months (AOR: 6.37, 95% CI: 3.85-10.54, p < 0.001), engaged in sexual activity at age 15 or younger (AOR: 3.67, 95% CI: 2.36-5.69, p < 0.001) and more likely to have ever been pregnant (AOR: 2.60, 95% CI: 1.24-5.45, p < 0.05) than those not in a relationship with either a Blesser or age-disparate partner. CONCLUSION: Different relationships present different HIV risk to AGYW. AGYW who had engaged in relationships with both a Blesser and an age-disparate partner were at greater HIV risk when examined against these relationships independent of one another. The data reveals the compounded HIV risk of being in both a transactional and age-disparate relationship.

Viral suppression among pregnant adolescents and women living with HIV in rural KwaZulu-Natal, South Africa: a cross sectional study to assess progress towards UNAIDS indicators and Implications for HIV Epidemic Control.

BACKGROUND: South Africa has made significant progress in scaling up antiretroviral therapy (ART) to achieve the aspirational goal of HIV epidemic control. The aim of this study was to determine the prevalence of HIV, assess progress towards each of the Joint United Nations Programme on HIV/AIDS (UNAIDS) indicators and determine factors associated with achieving viral suppression among pregnant adolescents and women living with HIV in rural KwaZulu-Natal, South Africa. METHODS: Pregnant adolescents and women, 12 years and older seeking antenatal care at six primary health care clinics were enrolled in a cross-sectional study. Following written informed consent, structured questionnaires were administered, and finger-prick blood samples were collected for HIV antibody testing and viral load measurement. Viral suppression was defined as HIV viral load of < 400 copies per mL. RESULTS: Between Dec 2016 and March 2017, among the 546 enrolled participants, data for 545 were analysed. The overall HIV prevalence was 40.2% [95% Confidence Interval (CI) 36.1-44.3]. Age-stratified prevalence increased from 22.1% (95% CI, 15.9-30.0) in the 14-19 year age group to 63.9% (95% CI, 55.1-71.9) among women ≥ 30 years (Χ2 trend P < 0.0001). Of the HIV positive participants, 84.5% (95% CI, 79.0-88.8) knew their HIV positive status, 98.3% (95% CI 95.1-99.4) who knew their status were on ART, and of those on ART, 95.9% (95% CI 91.8-98.0) were virally suppressed. Among all HIV-positives 90.8% (95% CI, 86.3-94.0) had achieved viral suppression, whilst those in the 14-19 year age group were least likely to be virally suppressed at 82.8% (95% CI 65.5-92.4) compared to those in the older age groups. Married women compared to those unmarried were more likely to have achieved viral suppression (PRR) of 1.11 (95% CI 1.05-1.18), P < 0.001. CONCLUSIONS: The proportion of HIV positive pregnant women achieving viral suppression was encouraging though far short of the target towards achieving epidemic control. Importantly, adolescent pregnant women were less likely to know their HIV status and to achieve viral suppression, underscoring the public health implications of sustained risk of HIV transmission. Thus, greater effort and strong social support are essential to improve HIV knowledge of status and care continuum towards the goal to achieving HIV epidemic control. To "fast-track" the response to achieve HIV epidemic control and end the AIDS epidemic, the Joint United Nations Programme on HIV/AIDS (UNAIDS) set ambitious HIV testing and treatment targets for people living with HIV. Meeting these targets through scaling up testing for HIV, initiating and sustaining antiretroviral therapy (ART) to maintain viral suppression provides both therapeutic and preventive benefits with the potential to reduce HIV transmission. Viral suppression among pregnant adolescents and women living with HIV is crucial for the prevention of mother-to-child transmission of HIV including onward transmission to sexual partners. As a public health approach, in South Africa all pregnant women are offered routine HIV testing and immediate initiation of lifelong ART irrespective of CD4 cell count. It is, therefore, important to ascertain progress towards reaching the targets. The proportion of HIV positive pregnant adolescents and women achieving viral suppression was encouraging though far short of the target towards achieving epidemic control. Importantly, pregnant adolescents were less likely to know their HIV status and to achieve viral suppression, underscoring the public health implications of sustained risk of HIV transmission. Thus, greater effort and strong social support are essential to improve HIV knowledge of status and care continuum towards the goal to achieving HIV epidemic control.

Impact of point-of-care testing and treatment of sexually transmitted infections and bacterial vaginosis on genital tract inflammatory cytokines in a cohort of young South African women.

OBJECTIVES: STIs cause inflammation that is detrimental for both HIV risk and reproductive health. We assessed the impact of point-of-care (POC) STI testing, immediate treatment and expedited partner therapy (EPT) on genital tract cytokines among a cohort of young South African women. METHODS: HIV-negative women underwent POC testing for Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG) and Trichomonas vaginalis (TV) by Xpert CT/NG and OSOM TV, and for bacterial vaginosis (BV) by microscopy. Women with STIs and/or BV received immediate treatment, EPT for STIs and retested after 6 and 12 weeks. Concentrations of 48 cytokines were measured in cervicovaginal fluid at each visit using multiplex ELISA technology. The impact of STI treatment on cytokine concentrations was assessed by multivariable linear mixed models and principal component analysis. RESULTS: The study enrolled 251 women with median age of 23 years (IQR 21-27). The prevalence of CT, NG and TV were 14.3%, 4.4% and 4.0%, and 34.3% had BV. Women with STIs or BV at baseline (n=94) had significantly higher concentrations of pro-inflammatory cytokines (interleukin (IL)-1α, IL-1ß, IL-6, tumour necrosis factor (TNF)-α, TNF-ß, IL-18 and macrophage inflammatory factor (MIF)) and chemokines (IL-8, IL-16, macrophage inflammatory protein (MIP)-1α, IFN-α2, monokine induced by gamma interferon (MIG), monocyte chemoattractant protein (MCP)-3, regulated on activation normal T cell expressed and secreted and eotaxin) compared with women without (n=157). STI treatment was strongly associated with reduced concentrations of pro-inflammatory cytokines IL-6 (p=0.004), IL-1ß (p=0.013), TNF-α (p=0.018) and chemokines MIG (p=0.008) and growth-related oncogene (GRO)-α (p=0.025). A lower Nugent score was associated with a reduction in pro-inflammatory cytokines IL-1α (p=0.003), TNF-related apoptosis-inducing ligand (p=0.004), MIF (p=0.010) and IL-18 (p<0.001), but an increase in chemokines MIG (p=0.020), GRO-α (p<0.001), IP-10 (p<0.001), MIP-1ß (p=0.008) and MCP-1 (p=0.005). Principal component analysis showed differences in STI and BV-related inflammatory profiles, but that resolution restored a profile consistent with vaginal health. CONCLUSIONS: A comprehensive STI intervention effectively reduced genital inflammation among young women, thereby improving vaginal health and potentially reducing HIV risk.

A Systematic Review of Randomized Controlled Trials of School Based Interventions on Sexual Risk Behaviors and Sexually Transmitted Infections Among Young Adolescents in Sub-Saharan Africa.

Young adolescents in Sub-Saharan Africa (SSA) are at high risk of involvement in sexual risk behaviors; and curable sexually transmitted infections (STI), herpes simplex virus type 2 (HSV-2), human immunodeficiency virus (HIV) and unintended pregnancies remain persistently high in this population. Evidence based strategies are urgently needed to improve these outcomes. The aim of this systematic review was to synthesize the evidence from randomized controlled trials (RCT) to determine whether school-based interventions promote safe sex behaviors, reduce sexual risk behaviors and risk of curable STIs, HSV-2, HIV and unintended pregnancies among young adolescents aged 9-19 years in SSA. Electronic databases were searched for published studies and manual searches were conducted through reviewing of references of cited literature in the English language up to December 2019. Two independent reviewers screened and abstracted the data. We identified 428 articles and data from nine RCTs (N = 14,426 secondary school students) that fulfilled the selection criteria were analysed. Two studies measured pregnancy as an outcome and showed significant declines in unintended pregnancies. Of the five studies that measured HIV/AIDS related-knowledge, condom-use outcomes (normative beliefs, knowledge, and self-efficacy) and attitudes to HIV testing, four showed significant improvements. Of the six studies that measured sexual debut, four reported moderate but non-significant declines and in two studies sexual debut information was either incomplete or unreliable. One study measured curable STIs and found no significant declines; whilst the second study that measured HSV-2 and HIV, no significant declines were observed. This review highlights the need to undertake well-designed research studies to provide evidence on the impact of interventions on curable STIs, HSV-2 and HIV, critical to improving the health of young adolescents.

Prevalence and Risk Factors for HIV Infection Among Heterosexual Men Recruited from Socializing Venues in Rural KwaZulu-Natal, South Africa.

Young heterosexual men have low uptake of HIV prevention and treatment services and represent an important key population that may require novel strategies. We recruited 1271 heterosexual men, 12 years and older from socializing venues such as "shebeens", transport hubs, "spaza" shops, and community centers in rural KwaZulu-Natal, South Africa. Participants completed a questionnaire and were tested for HIV serostatus. Generalized estimating equations (GEE) with exchangeable covariance structure estimated factors independently associated with prevalent HIV infection. Median age was 25 years [Interquartile range (IQR) 21-29]. HIV prevalence was 15.5% [95% confidence interval (CI) 11.0-21.9] and increased significantly by age. Factors associated with higher odds of HIV infection were being 25 years and older [adjusted odds ratio (aOR) 4.82, 95% CI 3.47-6.69; p < 0.001), not completing high school (aOR 1.60, 95% CI 1.39-1.85; p < 0.001), not using condoms at first sex (aOR 1.43, 95% CI 1.20-1.70; p < 0.001), consuming alcohol (aOR 1.63, 95% CI 1.15-2.31; p = 0.006) or substances (aOR 1.37, 95% CI 1.31-1.44; p < 0.001), and absence of medical circumcision (aOR 2.05, 95% CI 1.71-2.44; p < 0.001). Risk was lower among those testing for HIV in last 12 months (aOR 0.54, 95% CI 0.36-0.80; p = 0.002). Greater effort is needed to implement innovative programs within settings that are easily accessible and where heterosexual men are likely to be.

Poor rates of linkage to HIV care and uptake of treatment after home-based HIV testing among newly diagnosed 15-to-49 year-old men and women in a high HIV prevalence setting in South Africa.

Early antiretroviral therapy (ART) initiation is essential, but linkage to care following community-based services is often poor, and inadequately understood. This study examined factors influencing linkage to care following home-based HIV-testing services (HBHTS) in a hyper-endemic setting in South Africa. HBHTS was offered to participants (N = 10,236) enrolled in the second HIV Incidence Provincial Surveillance System survey (2015-2016), KwaZulu-Natal. Follow-up telephone surveys with 196 of the 313 individuals diagnosed HIV-positive through HBHTS were used to measure linkage to care (i.e., a clinic visit within 12 weeks) and ART-initiation. Among newly diagnosed individuals (N = 183), 55% linked to care, and 21% of those who were ART-eligible started treatment within 12 weeks. Linkage to care was less likely among participants who had doubted their HIV-diagnosis (aOR:0.46, 95%CI: 0.23-0.93) and more likely among participants who had disclosed their HIV-status (aOR:2.31, 95%CI: 1.07-4.97). Reasons for not linking to care included no time (61%), only wanting to start treatment when sick (48%), fear of side-effects (33%), and not believing the HIV-diagnosis (16%). Results indicate that HBHTS needs to be paired with targeted interventions to facilitate early linkage to care. Interventions are required to counter denial of HIV status and facilitate early linkage to care among healthier individuals.

Association of medical male circumcision and sexually transmitted infections in a population-based study using targeted maximum likelihood estimation.

BACKGROUND: Epidemiological theory and many empirical studies support the hypothesis that there is a protective effect of male circumcision against some sexually transmitted infections (STIs). However, there is a paucity of randomized control trials (RCTs) to test this hypothesis in the South African population. Due to the infeasibility of conducting RCTs, estimating marginal or average treatment effects with observational data increases interest. Using targeted maximum likelihood estimation (TMLE), a doubly robust estimation technique, we aim to provide evidence of an association between medical male circumcision (MMC) and two STI outcomes. METHODS: HIV and HSV-2 status were the two primary outcomes for this study. We investigated the associations between MMC and these STI outcomes, using cross-sectional data from the HIV Incidence Provincial Surveillance System (HIPSS) study in KwaZulu-Natal, South Africa. HIV antibodies were tested from the blood samples collected in the study. For HSV-2, serum samples were tested for HSV-2 antibodies via an ELISA-based anti-HSV-2 IgG. We estimated marginal prevalence ratios (PR) using TMLE and compared estimates with those from propensity score full matching (PSFM) and inverse probability of treatment weighting (IPTW). RESULTS: From a total 2850 male participants included in the analytic sample, the overall weighted prevalence of HIV was 32.4% (n = 941) and HSV-2 was 53.2% (n = 1529). TMLE estimates suggest that MMC was associated with 31% lower HIV prevalence (PR: 0.690; 95% CI: 0.614, 0.777) and 21.1% lower HSV-2 prevalence (PR: 0.789; 95% CI: 0.734, 0.848). The propensity score analyses also provided evidence of association of MMC with lower prevalence of HIV and HSV-2. For PSFM: HIV (PR: 0.689; 95% CI: 0.537, 0.885), and HSV-2 (PR: 0.832; 95% CI: 0.709, 0.975). For IPTW: HIV (PR: 0.708; 95% CI: 0.572, 0.875), and HSV-2 (PR: 0.837; 95% CI: 0.738, 0.949). CONCLUSION: Using a TMLE approach, we present further evidence of a protective association of MMC against HIV and HSV-2 in this hyper-endemic South African setting. TMLE has the potential to enhance the evidence base for recommendations that embrace the effect of public health interventions on health or disease outcomes.

Evaluating DREAMS HIV prevention interventions targeting adolescent girls and young women in high HIV prevalence districts in South Africa: protocol for a cross-sectional study.

BACKGROUND: Young women in sub-Saharan Africa remain at the epicentre of the HIV epidemic, with surveillance data indicating persistent high levels of HIV incidence. In South Africa, adolescent girls and young women (AGYW) account for a quarter of all new HIV infections. Determined, Resilient, Empowered, AIDS-free, Mentored and Safe (DREAMS) is a strategy introduced by the United States President's Emergency Plan for AIDS Relief (PEPFAR) aimed at reducing HIV incidence among AGYW in 10 countries in sub-Saharan Africa by 25% in the programme's first year, and by 40% in the second year. This study will assess the change in HIV incidence and reduction in risk associated behaviours that can be attributed to the DREAMS initiative in South Africa, using a population-based cross-sectional survey. METHODS: Data will be collected from a household-based representative sample of AGYW (between the ages 12-24 years) in four high prevalence districts (more than 10% of the population have HIV in these districts) in South Africa in which DREAMS has been implemented. A stratified cluster-based sampling approach will be used to select eligible participants for a cross-sectional survey with 18,500, to be conducted over 2017/2018. A questionnaire will be administered containing questions on sexual risk behaviour, selected academic and developmental milestones, prevalence of gender based violence, whilst examining exposure to DREAMS programmes. Biological samples, including two micro-containers of blood and self-collected vulvovaginal swab samples, are collected in each survey to test for HIV infection, HIV incidence, sexually transmitted infections (STIs) and pregnancy. This study will measure trends in population level HIV incidence using the Limiting antigen (LAg) Avidity Enzyme Immuno-Assay (EIA) and monitor changes in HIV incidence. DISCUSSION: Ending the HIV/AIDS pandemic by 2030 requires the continual monitoring and evaluation of prevention programmes, with the aim of optimising efforts and ensuring the achievement of epidemic control. This study will determine the impact DREAMS interventions have had on HIV incidence among AGYW in a 'real world, non-trial setting'.

Age-disparate partnerships and HSV-2 among adolescent girls and young women in South Africa: implications for HIV infection risk.

OBJECTIVE: There is an urgent need to understand high HIV-infection rates among young women in sub-Saharan Africa. While age-disparate partnerships have been characterised with high-risk sexual behaviours, the mechanisms through which these partnerships may increase HIV-risk are not fully understood. This study assessed the association between age-disparate partnerships and herpes simplex virus type-2 (HSV-2) infection, a factor known to increase HIV-infection risk. METHODS: Cross-sectional face-to-face questionnaire data, and laboratory HSV-2 and HIV antibody data were collected among a representative sample in the 2014/2015 household survey of the HIV Incidence Provincial Surveillance System in KwaZulu-Natal, South Africa. Among 15-24-year-old women who reported having ever had sex (n=1550), the association between age-disparate partnerships (ie, male partner ≥5 years older) and HSV-2 antibody status was assessed using multivariable Poisson regression models with robust variance. Analyses were repeated among HIV-negative women. RESULTS: HSV-2 prevalence was 55% among 15-24-year-old women. Women who reported an age-disparate partnership with their most recent partner were more likely to test HSV-2 positive compared with women with age-similar partners (64% vs 51%; adjusted prevalence ratio (aPR):1.19 (95% CI 1.07 to 1.32, p<0.01)). HSV-2 prevalence was also significantly higher among HIV-negative women who reported age-disparate partnerships (51% vs 40 %; aPR:1.25 (95% CI 1.05 to 1.50, p=0.014)). CONCLUSIONS: Results indicate that age-disparate partnerships are associated with a greater risk of HSV-2 among young women. These findings point towards an additional mechanism through which age-disparate partnerships could increase HIV-infection risk. Importantly, by increasing the HSV-2 risk, age-disparate partnerships have the potential to increase the HIV-infection risk within subsequent partnerships, regardless of the partner age-difference in those relationships.

Impact of HIV testing and treatment services on risky sexual behaviour in the uMgungundlovu District, KwaZulu-Natal, South Africa: a cross-sectional study.

INTRODUCTION: The South African public health system plays an important role in the delivery of HIV testing and treatment services. The health system is also an important conduit for targeted behaviour change communication with the expectation that clients who undergo counselling from health personnel, adopt safer sexual practices. Literature remains mixed on the impact these HIV services have on risky sexual behaviour. This analysis examines the sexual behaviour of clients following the utilisation of HIV testing and treatment services in Kwazulu-Natal, South Africa. METHODS: Data were used from two consecutive cross-sectional household surveys undertaken from June 2014 to June 2015 (2014/2015 survey) and from July 2015 to June 2016 (2015/2016 survey) in the uMgungundlovu District of KwaZulu-Natal, South Africa. Collectively, 20,048 randomly selected individuals aged 15 to 49 years old were interviewed across the two surveys. Utilisation of HIV testing and treatment services were used as independent variables and three sexual risk behaviours were used as dependent variables. Multiple regression models assessed the impact HIV testing and treatment services had on sexual risk behaviour while controlling for socio-demographic characteristics. RESULTS: Having tested for HIV had no association with any of the three sexual risk behaviours. However, receiving an HIV positive diagnosis reduced the likelihood of using condoms inconsistently with the respondents' most recent partner (AOR: 0.64; 95% CI 0.54-0.77). Antiretroviral use was negatively associated with inconsistent condom use (AOR: 0.45; 95% CI 0.35-0.58) and number of sexual partners in the previous year (AOR: 0.61; 95% CI 0.46-0.81). CONCLUSIONS: Results indicate that HIV testing and treatment services and the assumed exposure of clients to behaviour change communication, had a limited effect in reducing risky sexual behaviour. Data suggests that the engagement between health personnel and individuals accessing HIV testing and treatment services does not necessarily translate into the adoption of safer sexual practices, with the exception of individuals testing positive for HIV and those on ARV treatment, who had adopted safer sexual practices.

Tenofovir Gel for the Prevention of Herpes Simplex Virus Type 2 Infection.

BACKGROUND: Globally, herpes simplex virus type 2 (HSV-2) infection is the most common cause of genital ulcer disease. Effective prevention strategies for HSV-2 infection are needed to achieve the goals of the World Health Organization global strategy for the prevention and control of sexually transmitted infections. METHODS: We assessed the effectiveness of pericoital tenofovir gel, an antiviral microbicide, in preventing HSV-2 acquisition in a subgroup of 422 HSV-2-negative women enrolled in the Centre for the AIDS Programme of Research in South Africa (CAPRISA) 004 study, a double-blind, randomized, placebo-controlled trial. Incident HSV-2 cases were identified by evidence of seroconversion on an HSV-2 IgG enzyme-linked immunosorbent assay between study enrollment and exit. A confirmatory analysis was performed by Western blot testing. RESULTS: The HSV-2 incidence rate was 10.2 cases per 100 person-years (95% confidence interval [CI], 6.8 to 14.7) among 202 women assigned to tenofovir gel, as compared with 21.0 cases per 100 person-years (95% CI, 16.0 to 27.2) among 222 women assigned to placebo gel (incidence rate ratio, 0.49; 95% CI, 0.30 to 0.77; P=0.003). The HSV-2 incidence rate among the 25 women with vaginal tenofovir concentrations of 10,000 ng per milliliter or more was 5.7 cases per 100 person-years, as compared with 15.5 cases per 100 person-years among the 103 women with no detectable vaginal tenofovir (incidence rate ratio, 0.37; 95% CI, 0.04 to 1.51; P=0.14). As confirmed by Western blot testing, there were 16 HSV-2 seroconversions among women assigned to tenofovir gel as compared with 36 among those assigned to the placebo gel (incidence rate ratio, 0.45; 95% CI, 0.23 to 0.82; P=0.005). CONCLUSIONS: In this study in South Africa, pericoital application of tenofovir gel reduced HSV-2 acquisition in women. (Funded by the U.S. Agency for International Development and others; ClinicalTrials.gov number, NCT00441298.).

Perceived HIV-related stigma among university students in South Africa: implications for HIV testing.

HIV-related stigma, and particularly perceived stigma, has a negative impact across the HIV care continuum. This study adds to our understanding of stigma by assessing how perceived stigma varies from one context to another and how such differences are associated with the location where individuals would prefer an HIV test. We used self-administered questionnaire data (n = 378) obtained from a convenience sample of students (18 years and older) attending a tertiary education institution in Durban, South Africa. Perceived stigma in the university environment was compared to perceived stigma in the home community environment. Multiple logistic regression analysis tested whether a higher level of perceived stigma in one setting was associated with a preference for HIV testing in the other setting. While levels of symbolic stigma and discrimination were low, a large proportion of the sample perceived that people living with HIV experience some form of stigmatisation in the home community and university environments (47% vs 41%, p = 0.09). A total of 31% reported less perceived stigma in the university environment. Students who perceived less stigma in the university environment were significantly more likely to report a preference for HIV testing at the university clinic rather than at a clinic in their community (aOR: 2.03; p < 0.01). Perceptions common across settings that people living with HIV experience stigmatisation are of great concern, especially for efforts to increase demand for HIV testing among young people. Results suggest that HIV-testing services in environments perceived to be less stigmatising than home communities could provide preferred alternatives for HIV testing.

Placental leptin mRNA expression and serum leptin levels in pre-eclampsia associated with HIV infection.

Leptin, primarily produced by adipocytes, is implicated in the development of pre-eclampsia. This study examines placental leptin production and serum leptin levels in HIV infected and uninfected normotensive and pre-eclamptic pregnancies. Placental leptin production was analysed by RT-PCR and serum leptin levels by ELISA in normotensive (n = 90) and pre-eclamptic (n = 90) pregnancies which were further stratified by HIV status. Placental leptin production was higher in pre-eclampsia compared to normotensive pregnancies irrespective of HIV status (p = .04). Serum leptin was non-significantly raised in HIV uninfected (p = .42) but lower in HIV-infected (p = .03) pre-eclampsia. The latter had lower BMI (p = .007) and triceps skin-fold thickness (p < .001) than the HIV uninfected groups with a significant correlation between serum leptin and triceps skin-fold thickness (p < .001), indicative of less adipose tissue in HIV-infected women with consequently lower serum leptin. Thus, serum leptin levels are not indicative of increased placental production when pre-eclampsia is associated with HIV infection.