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This strategy was broken into two frameworks: I the first i to determine whether broadly protective antibodies could reduce HIV acquisition, that is could a vaccine regimen that elicited high levels of non-neutralizing antibodies be developed that would enhance the protective efficacy beyond that seen in RV144; I and second i , to discern whether neutralizing antibodies could actually prevent acquisition. HIV vaccine development has become a process of stepwise learning of how to make a vaccine that induces an immune response that is markedly better than the human immune response to HIV. Keywords: HIV vaccine; clinical trials; broadly neutralizing antibodies EN HIV vaccine clinical trials broadly neutralizing antibodies 1 3 3 06/05/21 20210501 NES 210501 Since the discovery that a retrovirus, human immunodeficiency virus type one (HIV-1), causes the acquired immune deficiency syndrome (AIDS), more than 77 million people have become infected with HIV and 37 million have died over the last 40 years [1]. Essentially the inability to elicit broadly neutralizing antibodies to HIV to cover its strain diversity has been a major flaw in the HIV vaccine field for the first 30 years of vaccine development. [Extracted from the article]

In the last 15 years, antiretroviral therapy (ART) has been the most globally impactful life-saving development of medical research. Antiretrovirals (ARVs) are used with great success for both the treatment and prevention of HIV infection. Despite these remarkable advances, this epidemic grows relentlessly worldwide. Over 2.1 million new infections occur each year, two-thirds in women and 240,000 in children. The widespread elimination of HIV will require the development of new, more potent prevention tools. Such efforts are imperative on a global scale. However, it must also be recognised that true containment of the epidemic requires the development and widespread implementation of a scientific advancement that has eluded us to date—a highly effective vaccine. Striving for such medical advances is what is required to achieve the end of AIDS. [ABSTRACT FROM AUTHOR]

The article offers information on the objectives of HIV innovation which is to reduce number of persons with HIV infection, as well as the long-term medical and economic burden of the pandemic. Topics discussed include reduction in HIV infection by early detection of HIV and the timely initiation of antiretroviral therapy (ART); information on inability of health care system leading to morbidity and mortality; and positive impact of vaccination over HIV prevention.

In a Perspective, Linda-Gail Bekker and Glenda Gray discuss HIV vaccine development. [ABSTRACT FROM AUTHOR]

Summary: Background: The HVTN 503/Phambili study, which assessed the efficacy of the Merck Ad5 gag/pol/nef subtype B HIV-1 preventive vaccine in South Africa, was stopped when futility criteria in the Step study (assessing the same vaccine in the Americas, Caribbean, and Australia) were met. Here we report long-term follow-up data. Methods: HVTN 503/Phambili was a double-blind, placebo-controlled, randomised trial that recruited HIV-1 uninfected, sexually active adults aged 18–35 years from five sites in South Africa. Eligible participants were randomly assigned (1:1) by computer-generated random numbers to either vaccine or placebo, stratified by site and sex. Cox proportional hazards models were used to estimate HIV-1 infection in the modified intention-to-treat cohort, all of whom were unmasked early in follow-up. The trial is registered with ClinicalTrials.gov, number NCT00413725 and the South African National Health Research Database, number DOH-27-0207-1539. Findings: Between Jan 24, 2007, and Sept 19, 2007, 801 participants (26·7%) of a planned 3000 were randomly assigned (400 to vaccine, 401 to placebo); 216 (27%) received only one injection, 529 (66%) received only two injections, and 56 (7%) received three injections. At a median follow-up of 42 months (IQR 31–42), 63 vaccine recipients (16%) had HIV-1 infection compared with 37 placebo recipients (9%; adjusted HR 1·70, 95% CI 1·13–2·55; p=0·01). Risk for HIV-1 infection did not differ according to the number of vaccinations received, sex, circumcision, or adenovirus type 5 (Ad5) serostatus. Differences in risk behaviour at baseline or during the study, or annualised dropout rate (7·7% [95% CI 6·2–9·5] for vaccine recipients vs 8·8% [7·1–10·7] for placebo recipients; p=0·40) are unlikely explanations for the increased rate of HIV-1 infections seen in vaccine recipients. Interpretation: The increased risk of HIV-1 acquisition in vaccine recipients, irrespective of number of doses received, warrants further investigation to understand the biological mechanism. We caution against further use of the Ad5 vector for HIV vaccines. Funding: National Institute of Allergy and Infectious Diseases, Merck, and South African Medical Research Council. [ABSTRACT FROM AUTHOR]

The Prevention of Mother-to-child Transmission (PMTCT) of HIV program in Zambia has undergone several policy iterations over the past 10 years. This qualitative study aimed to contribute towards addressing this knowledge gap by analysing the evolution and actors' influence during the policy process using the Walt and Gilson policy triangle as our evaluation framework. Document review and key informant interviews with policy makers were undertaken to identify the contextual factors that had shaped the PMTCT policy evolution in Zambia. Overall, the study revealed that over the past decade, at least five PMTCT policy changes have occurred, averaging three years per policy with extensive overlap between policies. This resulted in more than two policies being implemented at a given time. Pressure from the international community and scientific evidence were the main drivers of policy change in Zambia, with local actors being mainly reactive. Among international agencies, UNICEF and WHO were the key actors who had driven the policy changes as they had the power and resources. The rapid changes, negatively impacted the health system, disrupted service delivery, which was unprepared to effectively and efficiently shift from one policy to another. [ABSTRACT FROM AUTHOR]

Summary: Background: The MRKAd5 HIV-1 gag/pol/nef subtype B vaccine was designed to elicit T-cell-mediated immune responses capable of providing complete or partial protection from HIV-1 infection or a decrease in viral load after acquisition. We aim to assess the safety and efficacy of the vaccine in South Africa, where the major circulating clade is subtype C. Methods: We did a phase 2b double-blind, randomised test-of-concept study in sexually active HIV-1 seronegative participants at five sites in South Africa. Randomisation was by a computer-generated random number sequence. The vaccine and placebo were given by intramuscular injection on a 0, 1, 6 month schedule. Our coprimary endpoints were a vaccine-induced reduction in HIV-1 acquisition and viral-load setpoint. These endpoints were assessed independently in the modified intention-to-treat (MITT) cohort with two-tailed significance tests stratified by sex. We assessed immunogenicity by interferon-γ ELISPOT in peripheral-blood mononuclear cells. After the lack of efficacy of the MRKAd5 HIV-1 vaccine in the Step study, enrolment and vaccination in our study was halted, treatment allocations were unmasked, and follow-up continued. This study is registered with the South Africa National Health Research Database, number DOH-27-0207-1539, and ClinicalTrials.gov, number NCT00413725. Findings: 801 of a scheduled 3000 participants, of whom 360 (45%) were women, were randomly assigned to receive either vaccine or placebo. 445 participants (56%) had adenovirus serotype 5 (Ad5) titres greater than 200, and 129 men (29%) were circumcised. 34 MITT participants in the vaccine group were diagnosed with HIV-1 (incidence rate 4·54 per 100 person-years) and 28 in the placebo group (3·70 per 100 person-years). There was no evidence of vaccine efficacy; the hazard ratio adjusted for sex was 1·25 (95% CI 0·76–2·05). Vaccine efficacy did not differ by Ad5 titre, sex, age, herpes simplex virus type 2 status, or circumcision. The geometric mean viral-load setpoint was 20 483 copies per mL (n=33) in the vaccine group and 34 032 copies per mL (n=28) in the placebo group (p=0·39). The vaccine elicited interferon-γ-secreting T cells that recognised both clade B (89%) and C (77%) antigens. Interpretation: The MRKAd5 HIV-1 vaccine did not prevent HIV-1 infection or lower viral-load setpoint; however, stopping our trial early probably compromised our ability to draw conclusions. The high incidence rates noted in South Africa highlight the crucial need for intensified efforts to develop an efficacious vaccine. Funding: The US National Institute of Allergy and Infectious Disease and Merck and Co Inc. [Copyright &y& Elsevier]

In this article, the author discusses the adolescents infected with HIV in South Africa. She states that most of HIV infections are acquired early, while average diagnosis age found to be 11-12 years of age, and decrease survival of HIV infected is due to the lack of access to antiretroviral therapy (ART) and delayed diagnosis. She also mentions that the American Academy of Pediatrics recommends that HIV status should be revealed to adolescents to inform them about their health.

The editorialists' reply to letters written in response to the article "Extended Antiretroviral Prophylaxis to Reduce Breast-Milk HIV-1 Transmission, " by N.I. Kumwenda, D.R. Hoover, L.M. Mofenson, et al. is presented.

The article discusses the effort being taken in the prevention of pediatric HIV infection. It is suggested that there has been an increase to improve the best regimens to drive down infection rates among infants without having to compromise the therapeutic response of antiretroviral therapy in women when patients eventually are prescribed medications for their health. It is suggested that 15 to 69.5 percent of HIV-infected women will develop resistance mutations to nevirapine after a single dose intervention to prevent mother-to-child transmission of HIV.

The article presents an overview of the ways HIV infection should be handled in pregnant women in order to reduce the risk the disease's transmission to newborns. A discussion of factors which affect mother to child transmission of HIV and of the ways pregnancy affects the progression of HIV is presented. The effects HIV virus infections can have on pregnancy and the outcomes of pregnancy are discussed. Guidelines for the clinical management of labour and delivery of children from HIV-positive women that have been issued by the British HIV Association are examined.

The article offers information on the aspirational necessity of human immunodeficiency viruses (HIV) prevention. Topics discussed include a long acting injectable or implantable antiretroviral that provides effective concentrations of effective drugs; mentions the development of an effective HIV vaccine has been a more difficult challenge; and also mentions the role of both neutralizing and non-neutralizing antibodies play in reducing HIV acquisition.

The authors reflect on breast feeding, antiretroviral prophylaxis and the transmission of HIV from mother to child through breast feeding in poor countries. The authors suggest that care givers and mothers in poor countries will continue to select treatment options that best suit their economic and psychological needs. They argue that science will need to adapt and design strategies to meet the needs of patients.

The article reports on the use of combined preventing mother-to-child transmission (PMTCT) with active case in determining for tuberculosis (TB) in Soweto, South Africa. TB is the preeminent manifestation of HIV infection and has become a leading cause of maternal mortality and morbidity in high HIV prevalence settings. The counselling session of the prevention of PMTCT program provides an opportunity to screen HIV-infected pregnant women for TB.

Background: The frequency of pain is reported to be high in people living with HIV, but valid comparisons between people living with HIV and HIV-negative cohorts are rare. We investigated whether HIV infection influenced frequency and characteristics of pain in adults undergoing voluntary testing for HIV. Setting: Participants were recruited from an HIV voluntary counseling and testing center at the Chris Hani Baragwanath Academic Hospital, Soweto, South Africa. Methods: Pain was assessed using the Wisconsin Brief Pain Questionnaire. Depressive and anxiety symptomatology was determined using the Hopkins Symptom checklist-25. We then stratified by HIV status. Results: Data from 535 black South Africans were analyzed: HIVinfected n = 70, HIV-uninfected n = 465. Overall, frequency of any current pain was high with 59% [95% confidence interval (CI): 55 to 63, n: 316/535] of participants reporting pain, with no difference related to HIV status: HIV-infected 50% (95% CI: 37 to 61, n: 35/ 70), HIV-uninfected 60% (95% CI: 56 to 65, n: 281/465). Pain intensity and number of pain sites were similar between the groups as were symptoms of anxiety and depression: mean Hopkins Symptom Checklist-25 1.72 (95% CI: 1.57 to 1.87) HIV-infected participants and 1.68 (95% CI: 1.63 to 1.73) HIV-uninfected participants. Univariate analysis showed female sex and greater depressive and anxiety symptomatology associated with pain. In a multivariable modeling, only depressive and anxiety symptomatology was retained in the model. Conclusion: The high frequency of pain found in both HIVinfected and HIV-uninfected individuals presenting at a voluntary counseling and testing center was more likely to be associated with depression and anxiety, than with the presence or absence of HIV. [ABSTRACT FROM AUTHOR]

Introduction: Reliable and timely laboratory results are crucial for monitoring the Prevention of the Mother-to-Child Transmission (PMTCT) cascade, particularly to enable early HIV diagnosis and early intervention. We sought to explore whether and how laboratory services have been prepared to absorb new testing requirements following PMTCT Test-and-Treat policy changes in three districts of Zambia. Method: We employed in-depth interviews and thematic data analysis, informed by the health system dynamic framework. Twenty-Six health workers were purposively selected and a document review of laboratory services in the context of PMTCT was undertaken. All face-to-face interviews were conducted in three local government areas in the Copperbelt Province (one urban and two rural) between February 2019 and July 2020. We extracted notes and markings from the transcripts for coding. Different codes were sorted into potential themes and the data extracted were put within the identified themes. Trustworthiness was confirmed by keeping records of all data field notes, transcripts, and reflexive journals. Results: The findings revealed that the health system inputs (infrastructure and supplies, human resources, knowledge, and information and finance) and service delivery were unequal between the rural and urban sites, and this affected the ability of health facilities to apply the new testing requirements, especially, in the rural-based health facilities. The major barriers identified include gaps in the capacity of the existing laboratory system to perform crucial PMTCT clinical and surveillance functions in a coordinated manner and insufficient skilled human resources to absorb the increased testing demands. The centralized laboratory system for HIV testing of mothers and exposed neonates meant facilities had to send specimens to other facilities and districts which resulted in high turnaround time and hence delayed HIV diagnosis. Conclusion: New guidelines implemented without sufficient capacitation of health system laboratory capacity severely limited the effectiveness of PMTCT program implementation. This study documented the areas relating to health system inputs and laboratory service delivery where greater support to enable the absorption of the new testing requirements is needed. [ABSTRACT FROM AUTHOR]

Introduction: In South Africa, the rate of HIV in the sex worker (SW) population is exceedingly high, but critical gaps exist in our understanding of SWs and the factors that make them vulnerable to HIV. This study aimed to estimate HIV prevalence among female sex workers (FSWs) in Soweto, South Africa, and to describe their sexual behavior and other factors associated with HIV infection. Methods: A cross-sectional, respondent-driven sampling (RDS) recruitment methodology was used to enroll 508 FSWs based in Soweto. Data were collected using a survey instrument, followed by two HIV rapid tests. Raw and RDS adjusted data were analyzed using a chi-squared test of association and multivariate logistic regression to show factors associated with HIV infection. Findings: HIV prevalence among FSWs was 53.6% (95% CI 47.5–59.9). FSWs were almost exclusively based in taverns (85.6%) and hostels (52.0%). Less than a quarter (24.4%) were under 25 years of age. Non-partner violence was reported by 55.5%, 59.6% of whom were HIV-infected. Advancing age, incomplete secondary schooling, migrancy and multiple clients increased the likelihood of HIV acquisition: >30 years of age was associated with a 4.9 times (95% CI 2.6–9.3) increased likelihood of HIV; incomplete secondary schooling almost tripled the likelihood (AOR 2.8, 95% CI 1.6–5.0); being born outside of the Gauteng province increased the likelihood of HIV 2.3 times (95% CI 1.3–4.0); and having more than five clients per day almost doubled the likelihood (AOR 1.9, 95% CI 1.1–3.2). Conclusion: Our findings highlight the extreme vulnerability of FSWs to HIV. Advancing age, limited education and multiple clients were risk factors associated with HIV, strongly driven by a combination of structural, biological and behavioral determinants. Evidence suggests that interventions need to be carefully tailored to the varying profiles of SW populations across South Africa. Soweto could be considered a microcosm of South Africa in terms of the epidemic of violence and HIV experienced by the SW population, which is influenced by factors often beyond an individual level of control. While describing a hitherto largely undocumented population of FSWs, our findings confirm the urgent need to scale up innovative HIV prevention and treatment programs for this population. [ABSTRACT FROM AUTHOR]

Background: Some mother-to-child transmission (MTCT) studies suggest that allelic variations of Fc gamma receptors (FcγR) play a role in infant HIV-1 acquisition, but findings are inconsistent. To address the limitations of previous studies, the present study investigates the association between perinatal HIV-1 transmission and FcγR variability in three cohorts of South African infants born to women living with HIV-1. Methods: This nested case-control study combines FCGR genotypic data from three perinatal cohorts at two hospitals in Johannesburg, South Africa. Children with perinatally-acquired HIV-1 (cases, n = 395) were compared to HIV-1-exposed uninfected children (controls, n = 312). All study participants were black South Africans and received nevirapine for prevention of MTCT. Functional variants were genotyped using a multiplex ligation-dependent probe amplification assay, and their representation compared between groups using logistic regression analyses. Results: FCGR3A gene duplication associated with HIV-1 acquisition (OR = 10.27; 95% CI 2.00–52.65; P = 0.005) as did the FcγRIIb-232TT genotype even after adjusting for FCGR3A copy number and FCGR3B genotype (AOR = 1.72; 95%CI 1.07–2.76; P = 0.024). The association between FcγRIIb-232TT genotype and HIV-1 acquisition was further strengthened (AOR = 2.28; 95%CI 1.11–4.69; P = 0.024) if adjusted separately for FCGR2C c.134-96C>T. Homozygous FcγRIIIb-HNA1a did not significantly associate with HIV-1 acquisition in a univariate model (OR = 1.42; 95%CI 0.94–2.16; P = 0.098) but attained significance after adjustment for FCGR3A copy number and FCGR2B genotype (AOR = 1.55; 95%CI 1.01–2.38; P = 0.044). Both FcγRIIb-232TT (AOR = 1.83; 95%CI 1.13–2.97; P = 0.014) and homozygous FcγRIIIb-HNA1a (AOR = 1.66; 95%CI 1.07–2.57; P = 0.025) retained significance when birthweight and breastfeeding were added to the model. The common FCGR2A and FCGR3A polymorphisms did not associate with HIV-1 acquisition. Conclusions: Collectively, our findings suggest that the FcγRIIb-232TT genotype exerts a controlling influence on infant susceptibility to HIV-1 infection. We also show a role for less studied variants–FCGR3A duplication and homozygous HNA1a. These findings provide additional insight into a role for FcγRs in HIV-1 infection in children. [ABSTRACT FROM AUTHOR]

Background: Accumulating data suggest that immune effector functions mediated through the Fc portion of HIV-1-specific immunoglobulin G (IgG) are a key component of HIV-1 protective immunity, affecting both disease progression and HIV-1 acquisition. Through studying Fc gamma receptor (Fc?R) variants known to alter IgG Fc-mediated immune responses, we indirectly assessed the role of Fc?R-mediated effector functions in modulating perinatal HIV-1 transmission risk. In this study, genotypic data from 79 HIV-1 infected mothers and 78 HIV-1 infected infants (transmitting cases) were compared to 234 HIV-1 infected mothers and 235 HIV-1 exposed-uninfected infants (non-transmitting controls). Associations, unadjusted and adjusted for multiple comparisons, were assessed for overall transmission and according to mode of transmission—intrapartum (n = 31), in utero (n = 20), in utero-enriched (n = 48). Results: The maternal FcγRIIIa-158V allele that confers enhanced antibody binding affinity and antibody-dependent cellular cytotoxicity capacity significantly associated with reduced HIV-1 transmission [odds ratio (OR) 0.47, 95 % confidence interval (CI) 0.28-0.79, P = 0.004; PBonf > 0.05]. In particular, the FcγRIIIa-158V allele was underrepresented in the in utero transmitting group (P = 0.048; PBonf > 0.05) and in utero-enriched transmitting groups (P = 0.0001; PBonf < 0.01). In both mother and infant, possession of an FcγRIIIb-HNA1b allotype that reduces neutrophil-mediated effector functions associated with increased transmission (OR 1.87, 95 % CI 1.08-3.21, P = 0.025; PBonf > 0.05) and acquisition (OR 1.91, 95 % CI 1.11-3.30, P = 0.020; PBonf > 0.05), respectively. Conversely, the infant FcγRIIIb-HNA1a∣1a genotype was significantly protective of perinatal HIV-1 acquisition (OR 0.42, 95 % CI 0.18-0.96, P = 0.040; PBonf > 0.05). Conclusions: The findings of this study suggest a potential role for FcγR-mediated effector functions in perinatal HIV-1 transmission. However, future studies are required to validate the findings of this study, in particular associations that did not retain significance after adjustment for multiple comparisons. [ABSTRACT FROM AUTHOR]

We report a 23% asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) Omicron carriage rate in participants being enrolled into a clinical trial in South Africa, 15-fold higher than in trials before Omicron. We also found lower CD4 + T-cell counts in persons with human immunodeficiency virus (HIV) strongly correlated with increased odds of being SARS-CoV-2 polymerase chain reaction (PCR) positive. [ABSTRACT FROM AUTHOR]

A 14-bp insertion/deletion (indel) within the 3′ untranslated region (3′UTR) that affects HLA-G expression has been associated with HIV-1 mother-to-child transmission (MTCT). However, other 3′UTR single nucleotide polymorphisms (SNPs) that influence HLA-G mRNA stability have been described but not analysed in the context of MTCT, and little is known about the role of HLA-G alleles. We examined HLA-G alleles and 3′UTR SNPs, including the 14-bp indel, in 216 mother–infant pairs from Johannesburg, South Africa. Mother–infant pairs were classified as HIV-1 non-transmitting (NT, n = 144) or HIV-1 transmitting (TR, n = 72) with either intrapartum (IP, n = 29) or in utero (IU, n = 19) infected infants. We found HLA-G allele, G ∗ 01:01:02 (in strong linkage disequilibrium with the 14-bp insertion) and +3187G SNP were significantly over-represented in IU-TR mothers compared to NT mothers ( P = 0.036, OR = 2.26; P = 0.011, OR = 2.96, respectively). These findings suggest that maternal HLA-G alleles and/or SNPs that might alter expression of HLA-G potentially influence IU HIV-1 MTCT. [ABSTRACT FROM AUTHOR]

Zambia is focusing on attaining HIV epidemic control by 2021, including eliminating Mother to Child Transmission (eMTCT) of HIV. However, there is little evidence to understand frontline healthcare workers' experience with the policy changes and the readiness of different health system elements to contribute to this goal. To understand frontline healthcare workers' experience of preventing mother-to-child transmission (PMTCT) of human immunodeficiency (HIV) policy changes and to explore the health system readiness to respond to rapid changes in PMTCT policy by using the health system dynamic framework. We conducted a qualitative study in which 35 frontline healthcare workers were selected and interviewed using a snowball sampling technique. All transcripts were analysed through thematic content analysis and deductive coding. Themes were derived and presented according to the health system dynamics framework. Among the ten elements of the health system dynamics framework, service delivery, context, and resources (i.e. infrastructure and supplies, knowledge and information, human resource, and finance) were critical in implementing the continuously evolving PMTCT policies. Furthermore, due to the fragmented primary health care platform in Zambia, non-governmental organisations (NGOs) were instrumental in ensuring that the PMTCT programme met the demand and requirements of the general population. Frontline healthcare workers who participated in the study described inequity in access to ART services due to the service delivery model employed in the selected study sites. The study highlights challenges when policies are implemented without consideration for the readiness, context, and capacity in which the policy is implemented. We offer lessons that can inform implementation of universal health coverage of antiretroviral therapy (ART), a strategy many countries have adopted, despite weak health systems. [ABSTRACT FROM AUTHOR]

A cornerstone of HIV prevention clinical trials is providing a combination prevention package to all trial participants. The elements included in that standard of care (SoC) package evolve as new prevention modalities are developed. Pre-exposure prophylaxis (PrEP) was recommended by the World Health Organization for persons at high risk of acquiring HIV, but not all countries immediately adopted those recommendations. The South African Medical Research Council (SAMRC) convened a summit to discuss issues relating to SoC and PrEP in HIV prevention clinical trials taking place in lower- to middle-income countries (LMIC). Policymakers, regulators, ethicists, experts in law, researchers, representatives of advocacy groups, and the HIV Vaccine Trials Network (HVTN) presented a framework within which SoC principles could be articulated. A group of subject matter experts presented on the regulatory, ethical, scientific, and historic framework of SoC in clinical trials, focusing on PrEP in South Africa. Summit participants discussed how and when to include new HIV treatment and prevention practices into existing clinical guidelines and trial protocols, as well as the opportunities for and challenges to scaling up interventions. The summit addressed challenges to PrEP provision, such as inconsistent efficacy amongst different populations and various biological, virological, and immunological explanations for this heterogeneity. Advocates and community members propagated the urgent need for accessible interventions that could avert HIV infection. The meeting recommended supporting access to PrEP in HIV prevention trials by (1) developing PrEP access plans for HIV vaccine trials, (2) creating a PrEP fund that would supply PrEP to sites conducting HIV prevention trials via a central procurement mechanism, and (3) supporting the safety monitoring of PrEP. This report summarizes the presentations and discussions from the summit in order to highlight the importance of SoC in HIV prevention clinical trials. [ABSTRACT FROM AUTHOR]

Background: HIV prevention trials are increasingly being conducted in sub-Saharan Africa. Women at risk for HIV are also at risk of pregnancy. To maximize safety, women agree to avoid pregnancy during trials, yet pregnancies occur. Using data from the HVTN 503/"Phambili" vaccine trial, we report pregnancy incidence during and after the vaccination period and identify factors, measured at screening, associated with incident pregnancy. Methods: To enrol in the trial, women agreed and were supported to avoid pregnancy until 1 month after their third and final vaccination ("vaccination period"), corresponding to the first 7 months of follow-up. Unsterilized women, pooled across study arms, were analyzed. Poisson regression compared pregnancy rates during and after the vaccination period. Cox proportional hazards regression identified associations with first pregnancy. Results: Among 352 women (median age 23 yrs; median follow-up 1.5 yrs), pregnancy incidence was 9.6/100 women-years overall and 6.8/100 w-yrs and 11.3/100 w-yrs during and after the vaccination period, respectively [Rate Ratio = 0.60 (0.32-1.14), p = 0.10]. In multivariable analysis, pregnancy was reduced among women who: enrolled at sites providing contraception on-site [HR = 0.43, 95% CI (0.22-0.86)]; entered the trial as injectable contraceptive users [HR = 0.37 (0.21-0.67)] or as consistent condom users (trend) [HR = 0.54 (0.28-1.04)]. Compared with women with a single partner of HIV-unknown status, pregnancy rates were increased among women with: a single partner whose status was HIV-negative [HR = 2.34(1.16-4.73)] and; 2 partners both of HIV-unknown status [HR = 4.42(1.59-12.29)]. Women with 2 more of these risk factors: marijuana use, heavy drinking, or use of either during sex, had increased pregnancy incidence [HR = 2.66 (1.24-5.72)]. Conclusions: It is possible to screen South African women for pregnancy risk at trial entry. Providing injectable contraception for free on-site and supporting consistent condom use may reduce incident pregnancy. Screening should determine the substance use, partnering, and HIV status of both members of the couple for both pregnancy and HIV prevention. [ABSTRACT FROM AUTHOR]

The article reports on the hypothesis that single-dose nevirapine (NVP) reduces immune activation, which in turn reduces the likelihood of transmission of mother-to-child transmission of HIV-1. Concentrations of cord and maternal blood plasma immune activation markers and neopterin in newborns whose mothers received NVP were compared. A biological explanation is presented for why HIV-1 infected infants exposed perinatally to antiretroviral drugs might experience hastened disease progression.

Some authors argue that there are no predictors of adherence to medication, while others proffer indicators of likely adherence. These contextual factors are wide-ranging and may be Interdependent. There are few studies of adherence in resource-poor settings. Of these, many were linked to particular trials whose conditions were highly controlled. For instance, the number of participants in the trial was small, the participants were strictly selected and they were offered much adherence support. These conditions will largely fall away with wider access to antiretroviral drugs (ARVs) such as South Africa is undertaking. Poor adherence remains one of the challenges to scaling-up access to ARVs, and, as such, the likely barriers to adherence need to be understood and countered. This study explores contextual factors -- such as disclosure, preparation for treatment, treatment meaning and treatment acceptance -- as aspects of lifestyle that can bear on adherence. Those who had disclosed were largely supported at household level, and after initial problems with adherence, participants adjusted and were able to include ARM treatment in their daily repertoire. Although the anticipation of stigma remains an obstacle to wide disclosure, antiretroviral therapy offers new hope and has the potential to impact on stigma. [ABSTRACT FROM AUTHOR]

Compares the antiviral efficacy and safety between GW433908 and Nelfinavir in antiretroviral therapy-naive HIV-1-infected patients. Performance of an international, multi-center, randomized, open-label study in antiretroviral therapy-naive HIV-infected adults; Clinical developments for the treatment of HIV; Background of abacavir and lamivudine.

Objective: A screening centre in Soweto, South Africa (SA), investigated high-risk human papillomavirus (HR-HPV), HIV, cervical cancer risk amongst women. Methods: This cross-sectional study (June 2018-March 2019) describes screening results (Roche Linear Array HPV test and Pap smear liquid based cytology) and history of screening (known HIV status, antiretroviral therapy [ART] use, previous Pap smears). Data were stratified by age group (18–29, 30+ years), HIV status, Pap smear results and tested for statistical significance. Results: Of 280 women, 20.4% were HIV-positive, 18.2% had abnormal Pap smears, 41.8% had HR-HPV. Of older women, 48.2% (n = 78/162) had never had a Pap smear. Of younger women, 89.0% (n = 105/118) never had a Pap smear, but had significantly more low-grade squamous intraepithelial lesions (LSIL) and other HR-HPV infection than older women (12.7%[n = 15/118] vs 4.9%[n = 8/162], p = 0.0193; and 49.2%[n = 58/118] vs 29.0%[n = 47/162], p = 0.0006; respectively). HIV-positive women had more abnormal cytology results and infection with other HR-HPV types or co-infection with other HR-HPV type(s)/HPV-16 compared to HIV-negative women (35.1%[n = 20/57] vs 13.9%[n = 31/223], p = 0.0002; 56.1%[n = 32/57] vs 32.7%[n = 73/223], p = 0.001; and 12.3%[n = 7/57] vs 4.9%[n = 11/223], p = 0.044; respectively). Of 57 HIV-positive women, 45.6% (n = 26) already knew their HIV status; of which 69.2% were on ART and 34.6% never had a Pap smear. Conclusion: South African women have high rates of HIV, Pap smear abnormalities and HR-HPV, with low cervical cancer screening coverage. SA cervical cancer screening policy excludes (undiagnosed) HIV-positive and HIV-negative women <30 years, both populations found to have high prevalence of HR-HPV. HPV-based primary screening from 25 years could improve outcomes. [ABSTRACT FROM AUTHOR]

The ubiquity of cellular phone (cellphone) use in young people's daily lives has emerged as a priority area of concern for youth mental health. This study measured the prevalence of depression and its association with high cellphone use among youth in Soweto and Durban, South Africa. We analysed cross-sectional, baseline survey data among youth aged 16–24 who participated in a dual-site cohort study, 'AYAZAZI', conducted from 2014 to 2017. The primary outcome was depression using the 10-item Center for Epidemiologic Studies Depression Scale, with a score of ≥ 10 indicating probable depression. Cellphone use was measured via self-reported average number of hours of active use, with 'high cellphone use' defined as daily usage of ≥ 8. Multivariable logistic regression models assessed the independent relationship between high cellphone use and probable depression, adjusting for potential confounders. Of 425 participants with a median age of 19 years (IQR = 18–21), 59.5% were young women. Overall, 43.3% had probable depression, with a higher prevalence among women (49.0% vs. 34.9%, P =.004). Nearly all (94.6%) owned a cellphone. About one-third (29.5%) reported spending ≥ 8 hours per day using their cellphone (39.3% of women vs. 14.9% of men, P <.001). In the overall adjusted model, youth reporting high daily cellphone use had higher odds of probable depression (aOR: 1.83, 95% CI: 1.16–2.90). In gender-stratified models, high daily cellphone use was associated with probable depression among women (aOR: 2.51, 95% CI: 1.47–4.31), but not among men (aOR: 0.87, 95% CI: 0.35–2.16). Among a cohort of South African youth, we found a high prevalence of probable depression and high cellphone use (30%). The findings indicate a need for intersectoral initiatives focused on meaningful mental health support for South African youth to support positive growth and development. [ABSTRACT FROM AUTHOR]

Background: Despite multiple available HIV prevention methods, the HIV epidemic continues to affect South Africa the most. We sought to understand willingness to use actual and hypothetical HIV prevention methods among participants enrolled in a preventative HIV vaccine efficacy trial in Soweto, South Africa.Methods: We conducted a qualitative study with 38 self-reporting HIV-uninfected and consenting 18-35 year olds participating in the HVTN 702 vaccine efficacy trial in Soweto. Using a semi-structured interview guide, five focus group discussions (FGDs) were held, stratified by age, gender and sexual orientation. The FGDs were composed of: (i) 10 heterosexual women aged 18-24 years; (ii) 9 heterosexual and bisexual women aged 25-35 years; (iii & iv) heterosexual men aged 25-35 years with 7 in both groups; and (v) 5 men aged 18-35 years who have sex with men. FGDs were audio-recorded, transcribed verbatim, translated into English and analysed using thematic analysis.Results: We present five main themes: (i) long-lasting methods are preferable; (ii) condoms are well-known but not preferred for use; (iii) administration route of HIV prevention method is a consideration for the user; (iv) ideal HIV prevention methods should blend into the lifestyle of the user; and the perception that (v) visible prevention methods indicate sexual indiscretion.Conclusions: The participants' candour about barriers to condom and daily oral pre-exposure prophylaxis (PrEP) use, and expressed preferences for long-lasting, discreet, lifestyle-friendly methods reveal a gap in the biomedical prevention market aiming to reduce sexually acquired HIV in South Africa. Product developers should consider long-acting injectable formulations, such as vaccines, passive antibodies and chemoprophylaxis, for HIV prevention technologies. Future innovations in HIV prevention products may need to address the desire for the method to blend easily into lifestyles, such as food-medication formulations. [ABSTRACT FROM AUTHOR]

New HIV infections continue relentlessly in southern Africa, demonstrating the need for a vaccine to prevent HIV subtype C. In South Africa, the country with the highest number of new infections annually, HIV vaccine research has been ongoing since 2003 with collaborative public-private-philanthropic partnerships. So far, 21 clinical trials have been conducted in South Africa, investigating seven viral vectors, three DNA plasmids, four envelope proteins, five adjuvants and three monoclonal antibodies. Active vaccine candidates have spanned subtypes A, B, C, E and multi-subtype mosaic sequences. All were well tolerated. Four concepts were investigated for efficacy: rAd5-gag/pol/nef showed increased HIV acquisition in males, subtype C ALVAC/gp120/MF59 showed no preventative efficacy, and the trials for the VRC01 monoclonal antibody and Ad26.Mos4.HIV/subtype C gp140/ aluminum phosphate are ongoing. Future trials are planned with DNA/viral vector plus protein combinations in concert with pre-exposure prophylaxis, and sequential immunization studies with transmitted/founder HIV envelope to induce broadly neutralizing antibodies. Finally, passive immunization trials are underway to build on the experience with VRC01, including single and combination antibody trials with an antibody derived from a subtype-C-infected South African donor. Future consideration should be given to the evaluation of novel strategies, for example, inactivated-whole-virus vaccines. [ABSTRACT FROM AUTHOR]

Introduction: South Africa is the HIV epidemic epicentre; however, non-communicable diseases (NCDs) will be the most common cause of death by 2030. To improve identification and initiation of care for HIV and NCDs, we assessed proportion of clients referred and linked to care (LTC) for abnormal/positive screening results and time to LTC and treatment initiation from a HIV Testing Services (HTS) Centre before and after integrated testing for NCDs with optional peer-navigated linkage to care. Materials and methods: This two-phase prospective study was conducted at an adult HTS Centre in Soweto, South Africa. Phase 1 (February-June 2018) utilised standard of care (SOC) HTS services (blood pressure [BP], HIV rapid diagnostic testing (RDT), sexually transmitted infections [STI]/Tuberculosis [TB] symptom screening) with passive referral for abnormal/positive results. Phase 2 (June 2018-March 2019) further integrated blood glucose/cholesterol/chlamydia RDT, with optional peer-navigated referral. Enrolled referred clients completed telephonic follow-up surveys confirming LTC/treatment initiation ≤3 months post-screening. Socio-demographics, screening results, time to LTC/treatment initiation, peer-navigated referral uptake were reported. Analysis included Fisher's exact, chi-squared, Kruskal Wallis, and Student's T-tests. Thematic analysis was conducted for open-ended survey responses. Results: Of all 320 referrals, 40.0% were HIV-infections, 11.9% STIs, 6.6% TB, and 28.8% high/low BP. Of Phase 2-only referrals, 29.4% were for glucose and 23.5% cholesterol. Integrated NCD-HTS had significantly more clients LTC for HIV (76.7%[n = 66/86] vs 52.4%[n = 22/42], p = 0.0052) and within a shorter average time (6–8 days [Interquartile range (IQR):1–18.5] vs 8–13 days [IQR:2–32]) as compared to SOC HTS. Integrated NCD-HTS clients initiated HIV/STIs/BP treatment on average more quickly as compared to SOC HTS (5 days for STIs [IQR:1–21], 8 days for HIV/BP [IQR:5–17 and 2–13, respectively] vs 10 days for STIs [IQR: 4–32], 19.5 days for HIV [IQR:6.5–26.5], 8 days for BP [IQR:2–29)]. Participants chose passive over active referral (89.1% vs 10.9%; p<0.0001). Participants rejecting peer-navigated referral preferred to go alone (55.7% [n = 39/70]). Non-LTC was due to being busy (41.1% [n = 39/95]) and not being ready/refusing treatment (31.6% [n = 30/95]). Normalised results assessed at referral clinic (49.7% [n = 98/196]), prescribed lifestyle modification/monitoring (30.9% [n = 61/196]), and poor clinic flow/congestion and/or further testing required (10.7% [n = 21/196]) were associated with non-treatment initiation. Conclusion: Same-day treatment initiation is not achieved across diseases, despite peer-navigated referral. There are psychosocial and health systems barriers at entry to care/treatment initiation. Additional research may identify best strategies for rapid treatment initiation. [ABSTRACT FROM AUTHOR]

Efficacious HIV-1 vaccination requires elicitation of long-lived antibody responses. However, our understanding of how different vaccine types elicit durable antibody responses is lacking. To assess the impact of vaccine type on antibody responses, we measured IgG isotypes against four consensus HIV antigens from 2 weeks to 10 years post HIV-1 vaccination and used mixed effects models to estimate half-life of responses in four human clinical trials. Compared to protein-boosted regimens, half-lives of gp120-specific antibodies were longer but peak magnitudes were lower in Modified Vaccinia Ankara (MVA)-boosted regimens. Furthermore, gp120-specific B cell transcriptomics from MVA-boosted and protein-boosted vaccines revealed a distinct signature at a peak (2 weeks after last vaccination) including CD19, CD40, and FCRL2-5 activation along with increased B cell receptor signaling. Additional analysis revealed contributions of RIG-I-like receptor pathway and genes such as SMAD5 and IL-32 to antibody durability. Thus, this study provides novel insights into vaccine induced antibody durability and B-cell receptor signaling. [ABSTRACT FROM AUTHOR]

The public sector delivery of male circumcision in the only public sector hospital in Soweto, South Africa was examined to gauge local capacity to deliver this procedure as an intervention for prevention of HIV acquisition. During the period from July 1998 to March 2006, approximately 360 procedures were performed per annum. Striking seasonal variations and the relatively few procedures performed may create challenges for program planning, if male circumcision is increased to a level required to have an impact on the incidence of HIV among this population. [ABSTRACT FROM AUTHOR]

Limited information on the prevalence and risk factors for chronic pain is available for developing countries. Therefore, we investigated the prevalence of chronic pain and the association between this pain and various personal and sociodemographic factors by including questions in the South Africa Demographic and Household Survey 2016. The survey was conducted by face-to-face interviews with a nationally representative sample of the adult population (ages 15 and older, n = 10,336). Chronic pain was defined as pain or discomfort that had been experienced all the time or on and off for 3 months or more. The prevalence of chronic pain was 18.3% (95% confidence interval [CI]: 17.0-19.7). Women were more likely than were men to have chronic pain (men = 15.8% [95% CI: 13.9-17.8]; woman = 20.1% [95% CI: 18.4-21.8]), and the prevalence of chronic pain increased from 11.3% (95% CI: 9.6-13.3) for the age range 15 to 24 years to 34.4% (95% CI: 30.6-38.4) for the age range over 65 years. The body sites affected most frequently were the limbs (43.6% [95% CI: 40.4-46.9]), followed by the back (30.5% [95% CI: 27.7-33.6]). This article presents the prevalence of chronic pain in the general population of a middle-income African country. These data give much needed insights into the burden of, and risk factors for, chronic pain in low-resource settings, and identify priority groups for intervention. [ABSTRACT FROM AUTHOR]

Background: While HIV Testing Services (HTS) have increased, many South Africans have not been tested. Non-communicable diseases (NCDs) are the top cause of death worldwide. Integrated NCD-HTS could be a strategy to control both epidemics. Healthcare service strategies depends partially on positive user experience. We investigated client satisfaction of services and clinic flow time of an integrated NCD-HTS clinic.Methods: This prospective, cross-sectional study evaluated HTS client satisfaction with an HTS clinic at two phases. Phase 1 (February-June 2018) utilised standard HTS services: counsellor-led height/weight/blood pressure measurements, HIV rapid testing, and symptoms screening for sexually transmitted infections/Tuberculosis. Phase 2 (June 2018-March 2019) further integrated counsellor-led obesity screening (body mass index/abdominal circumference measurements), rapid cholesterol/glucose testing; and nurse-led Chlamydia and human papilloma virus (HPV)/cervical cancer screening. Socio-demographics, proportion of repeat clients, clinic flow time, and client survey data (open/closed-ended questions using five-point Likert scale) are reported. Fisher's exact test, chi-square analysis, and Kruskal Wallis test conducted comparisons. Multiple linear regression determined predictors associated with clinic time. Content thematic analysis was conducted for free response data.Results: Two hundred eighty-four and three hundred thirty-three participants were from Phase 1 and 2, respectively (N = 617). Phase 1 participants were significantly older (median age 36.5 (28.0-43.0) years vs. 31.0 (25.0-40.0) years; p = 0.0003), divorced/widowed (6.7%, [n = 19/282] vs. 2.4%, [n = 8/332]; p = 0.0091); had tertiary education (27.9%, [n = 79/283] vs. 20.1%, [n = 67/333]; p = 0.0234); and less female (53.9%, [n = 153/284] vs 67.6%, [n = 225/333]; p = 0.0005), compared to Phase 2. Phase 2 had 10.2% repeat clients (n = 34/333), and 97.9% (n = 320/327) were 'very satisfied' with integrated NCD-HTS, despite standard HTS having significantly shorter median time for counsellor-led HTS (36.5, interquartile range [IQR]: 31.0-45.0 vs. 41.5, IQR: 35.0-51.0; p < 0.0001). Phase 2 associations with longer clinic time were clients living together/married (est = 6.548; p = 0.0467), more tests conducted (est = 3.922; p < 0.0001), higher overall satisfaction score (est = 1.210; p = 0.0201). Those who matriculated experienced less clinic time (est = - 7.250; p = 0.0253).Conclusions: It is possible to integrate counsellor-led NCD rapid testing into standard HTS within historical HTS timeframes, yielding client satisfaction. Rapid cholesterol/glucose testing should be integrated into standard HTS. Research is required on the impact of cervical cancer/HPV screenings to HTS clinic flow to determine if it could be scaled up within the public sector. [ABSTRACT FROM AUTHOR]

Background: The HIV epidemiology in South Africa reveals stark age and gender disparities, with young women being the most vulnerable to HIV acquisition in 2017. Evaluation of HIV exposure is a challenge in HIV prevention research. Intermittent in-clinic interviewer-administered risk behaviour assessments are utilised but may be limited by social desirability and recall biases. We piloted a mobile phone application for daily self-report of sexual risk behaviour in fifty 18–25 year old women at risk of HIV infection enrolled in HIV Vaccine Trials Network 915 (HVTN 915) in Soweto, South Africa. Through a mixed-methods investigation, we explored barriers and facilitators to completing daily mobile phone surveys among HVTN 915 study participants and staff. Methods: We analysed quantitative data on barriers and facilitators to mobile phone study completion collected during the larger HVTN 915 study as well as two post-study focus group discussions (FGDs) with fifteen former participants with a median age of 24 years (IQR 23–25) and six individual in-depth interviews (IDIs) with HVTN 915 staff. FGDs and IDIs utilised semi-structured interview guides, were audio-recorded, transcribed verbatim and translated to English. After coding, thematic analysis was performed. Results: The main facilitator for daily mobile phone survey completion assessed across 336 follow-up visits for 49 participants was the daily short message system (SMS) reminders (93%, 312/336). Across 336 visits, 31/49 (63%) retained participants reported barriers to completion of daily mobile phone surveys: forgetting (20%, 12/49), being too busy (19%, 11/49) and the survey being an inconvenience (15%, 9/49). Five main themes were identified during the coding of IDIs and FGDs: (1) facilitators of mobile phone survey completion, such as daily SMS reminders and follow up calls for non-completers; (2) barriers to mobile phone survey completion, including partner, time-related and technical barriers; (3) power of incentives; (4) response bias in providing sensitive information, and (5) recommendations for future mobile phone based interventions. Conclusion: Despite our enthusiasm to use innovation to optimise sexual risk assessments, technical and practical solutions are required to improve implementation. We recommend further engagement with participants to optimise this approach and to further understand social desirability bias and study incentives in sexual risk reporting. [ABSTRACT FROM AUTHOR]

In the RV144 trial, vaccine-induced V1V2 IgG correlated with decreased HIV-1 risk. We investigated circulating antibody specificities in two phase 1 poxvirus prime-protein boost clinical trials conducted in South Africa: HVTN 097 (subtype B/E) and HVTN 100 (subtype C). With cross-subtype peptide microarrays and multiplex binding assays, we probed the magnitude and breadth of circulating antibody responses to linear variable loop 2 (V2) and conformational V1V2 specificities. Antibodies targeting the linear V2 epitope, a correlate of decreased HIV-1 risk in RV144, were elicited up to 100% and 61% in HVTN 097 and HVTN 100, respectively. Despite higher magnitude of envelope-specific responses in HVTN 100 compared to HVTN 097 (p's < 0.001), the magnitude and positivity for V2 linear epitope and V1V2 proteins were significantly lower in HVTN 100 compared to HVTN 097. Meanwhile, responses to other major linear epitopes including the variable 3 (V3) and constant 5 (C5) epitopes were higher in HVTN 100 compared to HVTN 097. Our data reveal substantial differences in the circulating antibody specificities induced by vaccination in these two canarypox prime-protein boost trials. Our findings suggest that the choice of viral sequences in prime-boost vaccine regimens, and potentially adjuvants and immunogen dose, influence the elicitation of V2-specific antibodies. [ABSTRACT FROM AUTHOR]

Background: South Africa has the highest number of people living with HIV (PLWH) and one of the largest antiretroviral therapy (ART) programs globally. High rates of substance use comorbidity exist, including speculation of recreational ART use (i.e., mixing ART with other illicit drugs). Recreational ART use may affect viral load among PLWH due to ART nonadherence and/or viral resistance; however, prior quantitative research has not examined rates of recreational ART use, nor associations with HIV treatment outcomes longitudinally.Methods: Data were drawn from a prospective, observational cohort study (n = 500) of ART-eligible adults recruited from two HIV voluntary counseling and testing centers in Cape Town, and Johannesburg, South Africa. Multiple logistic regression models assessed recreational ART use as a predictor of ART initiation over six months and viral load suppression over nine months, above and beyond other substance use (binge drinking and illicit drug use).Results: Approximately 5% (n = 24) reported recreational ART use, which was less frequent in Cape Town compared to Johannesburg (AOR = 0.025; 95%CI: 0.003-0.19; p < 0.001). Recreational ART use was not significantly associated with ART initiation or viral suppression. Other substance use, but not recreational ART use, was significantly associated with lower odds of ART initiation (AOR = 0.54; 95%CI: 0.33-0.87; p = .01) and viral suppression (AOR = 0.47; 95%CI: 0.25-0.89; p = .02).Conclusions: Recreational ART use was infrequent and not uniquely associated with ART initiation or viral suppression. Findings suggest that comorbid use of other substances is ultimately what may make recreational ART use problematic for ongoing engagement in care and viral suppression. [ABSTRACT FROM AUTHOR]

Background: Vaginal practices (VP) may adversely affect normal vaginal flora and mucosal integrity, and increase acquisition risk of HIV and other genital tract infections. Objective: The aim of this study was to describe self-reported VP, changes in the reported number of VP over time and factors associated with VP in a cohort of young Sowetan women enrolled in the HVTN 915 observational study. Method: We longitudinally assessed self-reported VP in 50 young women at risk of HIV acquisition aged 18–25 years in a prospective study over 3 months in Soweto, South Africa. Interviewer-administered HIV behavioural risk questionnaires were completed. No intervention to reduce VP was specified per protocol, but clinicians provided education at their discretion. The generalised estimating equation with inverse probability weights assessed VP over time. Results: The mean age at screening was 22 years; women reported multiple sexual partnerships with a mean of one main and 2 casual partners in the last 30 days. Consistent condom use was 2% (n = 1), 25% (n = 12) and 43% (n = 3) with main, casual and new partners, respectively. Commonly reported VP included washing the vagina with water (44%) and using fingers (48%). VP decreased significantly over time (p < 0.001). Women who used condoms inconsistently or whose last sex was with a casual partner were 3 times more likely to report VP (p = 0.001). Conclusion: Despite the high incidence of HIV in our setting, VP are still common and are associated with other behavioural risks for HIV. Further study is needed to assess whether clinician education may reduce VP and therefore should be included in HIV risk reduction counselling. [ABSTRACT FROM AUTHOR]

Background: Sex workers in South Africa are exposed to high levels of violence, yet little is known about their mental health needs. This study aims to understanding the prevalence of depression and post-traumatic stress disorder (PTSD) and their risk factors amongst female sex worker (FSWs) in Soweto, South Africa. Methods: A cross-sectional, respondent-driven sampling (RDS) survey enrolled 508 FSWs. Raw and RDS adjusted data were analyzed using a chi-squared test of association and multinomial regression for risk factors associated with depression and PTSD. Findings: Symptoms of severe depression were prevalent amongst 68.7%, PTSD was 39.6%, and 32.7% suffered from comorbid PTSD and depression. Experiencing ≥3 kinds of violence increased the likelihood of comorbidity (RRR4.11, 95% CI 1.52–11.12,p = 0.005). Internalised stigma increased the likelihood of one mental health condition (RRR1.25, 95% CI 1.10–1.42,p = 0.001), higher self-esteem was associated with independent (RRR1.14, 95% CI 1.05–1.25,p = 0.002) and comorbid conditions (RRR1.17, 95% CI 1.07–1.27,p = 0.001). Conclusion: Our findings highlight the sizable burden of treatable mental health conditions among FSWs in Soweto. This was driven by multiple exposures to violence, sex work related discrimination and overall moderate levels of self-esteem masking defence mechanisms. This suggests the urgent need to design and integrate services geared to the mental health needs for this population. [ABSTRACT FROM AUTHOR]

Background: HIV drug resistance (HIVDR) poses a threat to future antiretroviral therapy success. Monitoring HIVDR patterns is of particular importance in populations such as sex workers (SWs), where documented HIV prevalence is between 34–89%, and in countries with limited therapeutic options. Currently in South Africa, there is a dearth in evidence and no ongoing surveillance of HIVDR amongst sex work populations. This study aims to describe the prevalence of HIVDR amongst a sample of female sex workers (FSWs) from Soweto, South Africa. Methodology: A cross-sectional, respondent driven sampling (RDS) recruitment methodology was used to enrol FSWs based in Soweto. Participants were tested for HIV and undertook a survey that included HIV knowledge and treatment status. Whole blood specimens were collected from HIV positive FSWs to measure for CD4 counts, viral load (VL) and perform HIVDR genotyping. Frequencies were determined for categorical variables and medians and interquartile ranges (IQR) for the continuous. Results: Of the 508 enrolled participants, 55% (n = 280) were HIV positive and of median age 32 (IQR: 20–51) years. Among the HIV positive, 51.8% (132/269) were defined as virologically suppressed (VL < 400 copies/ml). Of the 119 individuals with unsuppressed viral loads who were successfully genotyped for resistance testing 37.8% (45/119) had detectable drug resistance. In this group, HIVDR mutations were found amongst 73.7% (14/19) of individuals on treatment, 27.4% (26/95) of individuals who were treatment naïve, and 100% (5/5) of defaulters. One phylogenetic cluster was found amongst treatment naïve FSWs. The K103N mutation was detected most commonly in 68.9% (31/45) individuals with HIVDR mutations, with 20/26 (76.9%) of treatment naïve FSW with detectable resistance having this mutation. The M184V mutation was found in both FSWs on treatment (12/14, 85.7%) and those defaulting (1/5, 20.0%). Discussion: More than one third (45/119) of the genotyped sample had HIVDR, with resistance to the NNRTI class being the most common. Almost half of HIV positive FSWs had unsuppressed viral loads, increasing the likelihood for onward transmission of HIV. Disturbingly, more than 1:4 treatment naïve women with unsuppressed viral loads had HIVDR suggesting that possible sexual transmission of drug resistance is occurring in this high-risk population. Given the high burden of HIVDR in a population with a high background prevalence of HIV, it is imperative that routine monitoring of HIVDR be implemented. Understanding transmission dynamics of HIVDR in FSW and its impact on treatment success should be urgently elucidated. [ABSTRACT FROM AUTHOR]

Alcohol and other drug use is prevalent among peri-urban, South African adolescents. We identified correlates of alcohol and other drug use by gender among adolescents (age = 16–18 years; N = 822) in peri-urban Johannesburg. Interviewer-administered surveys assessed sexual activity, alcohol and other drug use, and relevant psychosocial factors. In separate logistic regression models of alcohol and other drug use stratified by gender, violence exposure and sexual activity were associated with alcohol use for both males and females. For females only, depressive symptoms were associated with drug use. For males only, being older and sexually active were associated with drug use. Substance use interventions for South African adolescents should consider psychological health, sexual health, and tailoring by gender. [ABSTRACT FROM AUTHOR]

Introduction: The current World Health Organization guideline for first line antiretroviral therapy (ART) in HIV-infected children recommends the use of abacavir and lamivudine as nucleoside backbones and no longer includes stavudine. We compared treatment outcomes with abacavir (ABC) versus stavudine (d4T) in a cohort of HIV-1 infected children 6 and 12 months after antiretroviral therapy was initiated. Methods: This was a retrospective case-cohort study, using programmatic data from children enrolled in the Paediatric Wellness Programme at the Perinatal HIV Research Unit in Soweto, South Africa between 2005 and 2013. Children on abacavir/stavudine who had initiated ART at age <3 years with a regimen including lamivudine and lopinavir/ritonavir and had at least one 6 or 12 month viral load result were eligible. All ABC cases identified were matched for age at ART initiation and gender to eligible d4T controls (1:2). Outcomes analysed at 6 and 12 months post ART initiation included virological failure, mortality, immunological failure and anthropometry. Chi-square tests compared categorical measures while Kruskal-Wallis compared continuous measures. Results: We identified 57 eligible ABC cases and selected 114 matched d4T controls. Overall, 57% were females and 89% started treatment at age <1year. The median age at ART initiation was 3.11 (IQR: 1.98–6.05) months. There was no difference in the proportion of children virologically suppressed between the groups at 6 (ABC 54.5% vs. d4T 67.0%, p = 0.125) and 12 (ABC 66.7% vs. d4T 71.6%, p = 0.53) months post ART-initiation. The proportion of children with adherence levels >90% for ABC and d4T were similar too (95% in ABC vs. 86% in d4T, p = 0.10). The proportion of children who died over 12 months was 3.5% in the ABC and 7.9% in the d4T group (p = 0.27). Similarly, the anthropometric measures were comparable. Conclusions: It is reassuring that in the short term, in this group of patients, the treatment outcomes were similar. [ABSTRACT FROM AUTHOR]

Background: HLA strongly influences human immunodeficiency virus type 1 (HIV-1) disease progression. A major contributory mechanism is via the particular HLA-presented HIV-1 epitopes that are recognized by CD8(+) T-cells. Different populations vary considerably in the HLA alleles expressed. We investigated the HLA-specific impact of the MRKAd5 HIV-1 Gag/Pol/Nef vaccine in a subset of the infected Phambili cohort in whom the disease-susceptible HLA-B*58:02 is highly prevalent.Methods: Viral loads, CD4(+) T-cell counts, and enzyme-linked immunospot assay-determined anti-HIV-1 CD8(+) T-cell responses for a subset of infected antiretroviral-naive Phambili participants, selected according to sample availability, were analyzed.Results: Among those expressing disease-susceptible HLA-B*58:02, vaccinees had a lower chronic viral set point than placebo recipients (median, 7240 vs 122 500 copies/mL; P = .01), a 0.76 log10 lower longitudinal viremia level (P = .01), and slower progression to a CD4(+) T-cell count of <350 cells/mm(3) (P = .02). These differences were accompanied by a higher Gag-specific breadth (4.5 vs 1 responses; P = .04) and magnitude (2300 vs 70 spot-forming cells/10(6) peripheral blood mononuclear cells; P = .06) in vaccinees versus placebo recipients.Conclusions: In addition to the known enhancement of HIV-1 acquisition resulting from the MRKAd5 HIV-1 vaccine, these findings in a nonrandomized subset of enrollees show an HLA-specific vaccine effect on the time to CD4(+) T-cell count decline and viremia level after infection and the potential for vaccines to differentially alter disease outcome according to population HLA composition.Clinical Trials Registration: NCT00413725, DOH-27-0207-1539. [ABSTRACT FROM AUTHOR]

The development of biomedical interventions to reduce acquisition of HIV-1 infection remains a global priority, however their potential effectiveness is challenged by very high HIV-1 envelope diversity. Two large prophylactic trials in high incidence, clade C epidemic regions in southern Africa are imminent; passive administration of the monoclonal antibody VRC01, and active immunization with a clade C modified RV144-like vaccines. We have created a large representative panel of C clade viruses to enable assessment of antibody responses to vaccines and natural infection in Southern Africa, and we investigated the genotypic and neutralization properties of recently transmitted clade C viruses to determine how viral diversity impacted antibody recognition. We further explore the implications of these findings for the potential effectiveness of these trials. A panel of 200 HIV-1 Envelope pseudoviruses was constructed from clade C viruses collected within the first 100 days following infection. Viruses collected pre-seroconversion were significantly more resistant to serum neutralization compared to post-seroconversion viruses (p = 0.001). Over 13 years of the study as the epidemic matured, HIV-1 diversified (p = 0.0009) and became more neutralization resistant to monoclonal antibodies VRC01, PG9 and 4E10. When tested at therapeutic levels (10ug/ml), VRC01 only neutralized 80% of viruses in the panel, although it did exhibit potent neutralization activity against sensitive viruses (IC50 titres of 0.42 μg/ml). The Gp120 amino acid similarity between the clade C panel and candidate C-clade vaccine protein boosts (Ce1086 and TV1) was 77%, which is 8% more distant than between CRF01_AE viruses and the RV144 CRF01_AE immunogen. Furthermore, two vaccine signature sites, K169 in V2 and I307 in V3, associated with reduced infection risk in RV144, occurred less frequently in clade C panel viruses than in CRF01_AE viruses from Thailand. Increased resistance of pre-seroconversion viruses and evidence of antigenic drift highlights the value of using panels of very recently transmitted viruses and suggests that interventions may need to be modified over time to track the changing epidemic. Furthermore, high divergence such as that observed in the older clade C epidemic in southern Africa may impact vaccine efficacy, although the correlates of infection risk are yet to be defined in the clade C setting. Findings from this study of acute/early clade C viruses will aid vaccine development, and enable identification of new broad and potent antibodies to combat the HIV-1 C-clade epidemic in southern Africa. [ABSTRACT FROM AUTHOR]

Background. The efficacy of condoms for protection against transmission of herpes simplex virus type 2 (HSV-2) has been examined in a variety of populations with different effect measures. Often the efficacy has been assessed as change in hazard of transmission with consistent vs inconsistent use, independent of the number of acts. Condom efficacy has not previously measured on a per-act basis. Methods. We examined the per-act HSV-2 transmission rates with and without condom use among 911 African HSV-2 and human immunodeficiency virus type 1 (HIV-1) serodiscordant couples followed for an average of 18 months in an HIV prevention study. Infectivity models were used to associate the log10 probability of HSV-2 transmission over monthly risk periods with reported numbers of protected and unprotected sex acts. Condom efficacy was computed as the proportionate reduction in transmission risk for protected relative to unprotected sex acts. Results. Transmission of HSV-2 occurred in 68 couples, including 17 with susceptible women and 51 with susceptible men. The highest rate of transmission was from men to women: 28.5 transmissions per 1000 unprotected sex acts. We found that condoms were differentially protective against HSV-2 transmission by sex; condom use reduced per-act risk of transmission from men to women by 96% (P < .001) and marginally from women to men by 65% (P = .060). Conclusions. Condoms are recommended as an effective preventive method for heterosexual transmission of HSV-2. [ABSTRACT FROM AUTHOR]