HIV-1 diversity among young women in rural South Africa: HPTN 068

Background South Africa has one of the highest rates of HIV-1 (HIV) infection world-wide, with the highest rates among young women. We analyzed the molecular epidemiology and evolutionary history of HIV in young women attending high school in rural South Africa. Methods Samples were obtained from the HPTN 068 randomized controlled trial, which evaluated the effect of cash transfers for school attendance on HIV incidence in women aged 13–20 years (Mpumalanga province, 2011–2015). Plasma samples from HIV-infected participants were analyzed using the ViroSeq HIV-1 Genotyping assay. Phylogenetic analysis was performed using 200 pol gene study sequences and 2,294 subtype C reference sequences from South Africa. Transmission clusters were identified using Cluster Picker and HIV-TRACE, and were characterized using demographic and other epidemiological data. Phylodynamic analyses were performed using the BEAST software. Results The study enrolled 2,533 young women who were followed through their expected high school graduation date (main study); some participants had a post-study assessment (follow-up study). Two-hundred-twelve of 2,533 enrolled young women had HIV infection. HIV pol sequences were obtained for 94% (n = 201/212) of the HIV-infected participants. All but one of the sequences were HIV-1 subtype C; the non-C subtype sequence was excluded from further analysis. Median pairwise genetic distance between the subtype C sequences was 6.4% (IQR: 5.6–7.2). Overall, 26% of study sequences fell into 21 phylogenetic clusters with 2–6 women per cluster. Thirteen (62%) clusters included women who were HIV-infected at enrollment. Clustering was not associated with study arm, demographic or other epidemiological factors. The estimated date of origin of HIV subtype C in the study population was 1958 (95% highest posterior density [HPD]: 1931–1980), and the median estimated substitution rate among study pol sequences was 1.98x10-3 (95% HPD: 1.15x10-3–2.81x10-3) per site per year. Conclusions Phylogenetic analysis suggests that multiple HIV subtype C sublineages circulate among school age girls in South Africa. There were no substantive differences in the molecular epidemiology of HIV between control and intervention arms in the HPTN 068 trial

Natural control of HIV infection in young women in South Africa: HPTN 068

Background: Some individuals control HIV replication without antiretroviral (ARV) therapy. Objective: To analyze viral suppression in young women in rural South Africa enrolled in a trial evaluating a behavioral intervention for HIV prevention. Methods: Plasma samples were obtained from women ages 13–24 (81 infected at enrollment, 164 seroconverters). ARV testing was performed using an assay that detects 20 ARV drugs. Women were classified as viremic controllers if they were virally suppressed for ≥12 months with no ARV drug use. Results: Samples from 216/245 (88.2%) women had no ARV drugs detected at their first HIV-positive visit. Thirty-four (15.7%) of the 216 women had a viral load <2,000 copies/mL. Fifteen of the 34 women were followed for ≥12 months; 12 were virally suppressed with no ARV drugs detected during follow-up. These women were classified as viremic controllers (overall: 12/216=5.6%). The median CD4 cell count at the first HIV-positive visit was higher among the 12 controllers than among the 204 women who were not using ARV drugs (759 vs. 549 cells/mm 3 , p=0.02). Some women had a viral load <40 copies/mL at a single study visit, but none were classified as elite controllers (viral load <40 copies/mL for ≥12 months with no ARV drug use). Conclusions: In this cohort, 5.6% of women who were not using ARV drugs had sustained viral suppression. This represents a minimum estimate of the frequency of viremic controllers in this cohort, since some women were not followed long enough to meet the criteria for classification