Summary Background The incidence of HIV infection in young women in Africa is very high. We did a large-scale community-wide phylogenetic study to examine the underlying HIV transmission dynamics and the source and consequences of high rates of HIV infection in young women in South Africa. Methods We did a cross-sectional household survey of randomly selected individuals aged 15–49 years in two neighbouring subdistricts (one urban and one rural) with a high burden of HIV infection in KwaZulu-Natal, South Africa. Participants completed structured questionnaires that captured general demographic, socioeconomic, psychosocial, and behavioural data. Peripheral blood samples were obtained for HIV antibody testing. Samples with HIV RNA viral load greater than 1000 copies per mL were selected for genotyping. We constructed a phylogenetic tree to identify clusters of linked infections (defined as two or more sequences with bootstrap or posterior support ≥90% and genetic distance ≤4.5%). Findings From June 11, 2014, to June 22, 2015, we enrolled 9812 participants, 3969 of whom tested HIV positive. HIV prevalence (weighted) was 59.8% in 2835 women aged 25–40 years, 40.3% in 1548 men aged 25–40 years, 22.3% in 2224 women younger than 25 years, and 7.6% in 1472 men younger than 25 years. HIV genotyping was done in 1589 individuals with a viral load of more than 1000 copies per mL. In 90 transmission clusters, 123 women were linked to 103 men. Of 60 possible phylogenetically linked pairings with the 43 women younger than 25 years, 18 (30.0%) probable male partners were younger than 25 years, 37 (61.7%) were aged 25–40 years, and five (8.3%) were aged 41–49 years: mean age difference 8.7 years (95% CI 6.8–10.6; p<0.0001). For the 92 possible phylogenetically linked pairings with the 56 women aged 25–40 years, the age difference dropped to 1.1 years (95% CI –0.6 to 2.8; p=0.111). 16 (39.0%) of 41 probable male partners linked to women younger than 25 years were also linked to women aged 25–40 years. Of 79 men (mean age 31.5 years) linked to women younger than 40 years, 62 (78.5%) were unaware of their HIV-positive status, 76 (96.2%) were not on antiretroviral therapy, and 29 (36.7%) had viral loads of more than 50 000 copies per mL. Interpretation Sexual partnering between young women and older men, who might have acquired HIV from women of similar age, is a key feature of the sexual networks driving transmission. Expansion of treatment and combination prevention strategies that include interventions to address age-disparate sexual partnering is crucial to reducing HIV incidence and enabling Africa to reach the goal of ending AIDS as a public health threat. Funding President’s Emergency Program for AIDS Relief, US Centers for Disease Control and Prevention, South African Medical Research Council, and MAC AIDS Fund.

Centers for Disease Control and Prevention and the US Presidents Emergency Plan for AIDS Relief (PEPFAR).

The President's Emergency Plan for AIDS Relief through the Centers for Disease Control and Prevention.

Background South Africa has the largest public antiretroviral therapy (ART) programme in the world. We assessed temporal trends in pretreatment HIV-1 drug resistance (PDR) in ART-naïve adults from South Africa. Methods We included datasets from studies conducted between 2000 and 2016, with HIV-1 pol sequences from more than ten ART-naïve adults. We analysed sequences for the presence of 101 drug resistance mutations. We pooled sequences by sampling year and performed a sequence-level analysis using a generalized linear mixed model, including the dataset as a random effect. Findings We identified 38 datasets, and retrieved 6880 HIV-1 pol sequences for analysis. The pooled annual prevalence of PDR remained below 5% until 2009, then increased to a peak of 11·9% (95% confidence interval (CI) 9·2-15·0) in 2015. The pooled annual prevalence of non-nucleoside reverse-transcriptase inhibitor (NNRTI) PDR remained below 5% until 2011, then increased to 10.0% (95% CI 8.4–11.8) by 2014. Between 2000 and 2016, there was a 1.18-fold (95% CI 1.13–1.23) annual increase in NNRTI PDR (p < 0.001), and a 1.10-fold (95% CI 1.05–1.16) annual increase in nucleoside reverse-transcriptase inhibitor PDR (p = 0.001). Interpretation Increasing PDR in South Africa presents a threat to the efforts to end the HIV/AIDS epidemic. These findings support the recent decision to modify the standard first-line ART regimen, but also highlights the need for broader public health action to prevent the further emergence and transmission of drug-resistant HIV. Source of Funding This research project was funded by the South African Medical Research Council (MRC) with funds from National Treasury under its Economic Competitiveness and Support Package. Disclaimer The contents of this publication are solely the responsibility of the authors and do not necessarily represent the official views of CDC.

Introduction: We describe the overall accuracy and performance of a serial rapid HIV testing algorithm used in community-based HIV testing in the context of a population-based household survey conducted in two sub-districts of uMgungundlovu district, KwaZulu-Natal, South Africa, against reference fourth-generation HIV-1/2 antibody and p24 antigen combination immunoassays. We discuss implications of the findings on rapid HIV testing programmes. Methods: Cross-sectional design: Following enrolment into the survey, questionnaires were administered to eligible and consenting participants in order to obtain demographic and HIV-related data. Peripheral blood samples were collected for HIV-related testing. Participants were offered community-based HIV testing in the home by trained field workers using a serial algorithm with two rapid diagnostic tests (RDTs) in series. In the laboratory, reference HIV testing was conducted using two fourth-generation immunoassays with all positives in the confirmatory test considered true positives. Accuracy, sensitivity, specificity, positive predictive value, negative predictive value and false-positive and false-negative rates were determined. Results: Of 10,236 individuals enrolled in the survey, 3740 were tested in the home (median age 24 years (interquartile range 19–31 years), 42.1% males and HIV positivity on RDT algorithm 8.0%). From those tested, 3729 (99.7%) had a definitive RDT result as well as a laboratory immunoassay result. The overall accuracy of the RDT when compared to the fourth-generation immunoassays was 98.8% (95% confidence interval (CI) 98.5–99.2). The sensitivity, specificity, positive predictive value and negative predictive value were 91.1% (95% CI 87.5–93.7), 99.9% (95% CI 99.8–100), 99.3% (95% CI 97.4–99.8) and 99.1% (95% CI 98.8–99.4) respectively. The false-positive and false-negative rates were 0.06% (95% CI 0.01–0.24) and 8.9% (95% CI 6.3–12.53). Compared to true positives, false negatives were more likely to be recently infected on limited antigen avidity assay and to report antiretroviral therapy (ART) use. Conclusions: The overall accuracy of the RDT algorithm was high. However, there were few false positives, and the sensitivity was lower than expected with high false negatives, despite implementation of quality assurance measures. False negatives were associated with recent (early) infection and ART exposure. The RDT algorithm was able to correctly identify the majority of HIV infections in community-based HIV testing. Messaging on the potential for false positives and false negatives should be included in these programmes.