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BackgroundPretreatment HIV drug resistance (PDR) undermines individual treatment success and threatens the achievement of UNAIDS 95-95-95 targets. In many African countries, limited data are available on PDR as detection of recent HIV infection is uncommon and access to resistance testing is limited. We describe the prevalence of PDR among South African women with recent HIV infection from the Evidence for Contraceptive Options and HIV Outcomes (ECHO) Trial.MethodsHIV-uninfected, sexually active women, aged 18-35 years, and seeking contraception were enrolled in the ECHO Trial at sites in South Africa, from 2015 to 2018. HIV testing was done at trial entry and repeated quarterly. We tested stored plasma samples collected at HIV diagnosis from women who seroconverted during follow-up and had a viral load >1000 copies/mL for antiretroviral resistant mutations using a validated laboratory-developed population genotyping assay, which sequences the full protease and reverse transcriptase regions. Mutation profiles were determined using the Stanford Drug Resistance Database.ResultsWe sequenced 275 samples. The median age was 23 years, and majority (98.9%, n = 272) were infected with HIV-1 subtype C. The prevalence of surveillance drug resistance mutations (SDRMs) was 13.5% (n = 37). Nonnucleoside reverse transcriptase inhibitor (NNRTI) mutations were found in 12.4% of women (n = 34). Few women had NRTI (1.8%, n = 5) and protease inhibitor (1.1%, n = 3) mutations. Five women had multiple NRTI and NNRTI SDRMs.ConclusionsThe high levels of PDR, particularly to NNRTIs, strongly support the recent change to the South African national HIV treatment guidelines to transition to a first-line drug regimen that excludes NNRTIs.

Supplemental Digital Content is Available in the Text., Background: HIV-1 risk scoring tools could help target provision of prevention modalities such as pre-exposure prophylaxis. Recent research suggests that risk scores for women aged 18–45 may not predict risk well among young women aged 18–24. We evaluated the predictive performance of age-specific risk scores compared with the existing non–age-specific VOICE risk score, developed for women aged 18–45. Methods: We conducted a secondary analysis of the Evidence for Contraceptive Options and HIV Outcomes Trial to develop and internally validate HIV-1 risk scores for women aged 18–24 and 25–35 in South Africa. Candidate predictors included baseline demographic, clinical, behavioral, and contextual characteristics readily available in clinical settings. The VOICE risk score was applied to women aged 18–35. We evaluated predictive performance of each risk score by area under the receiver operating characteristic curve (AUC). Results: Predictive performance of all risk scores was moderate, with AUC (95% confidence interval) of 0.64 (0.60 to 0.67) among women aged 18–24, 0.68 (0.62 to 0.73) among those aged 25–35, and 0.61 (0.58 to 0.65) for the VOICE risk score applied to women aged 18–35; The AUC was similar in internal validation. Among women aged 18–24, HIV-1 incidence was high even at low risk scores, at 3.9 per 100 person-years (95% confidence interval: 3.2 to 4.7). Conclusions: All risk scores were moderately predictive of HIV-1 acquisition, and age-specific risk scores performed only marginally better than the VOICE non–age-specific risk score. Approaches for targeted pre-exposure prophylaxis provision to women in South Africa may require more extensive data than are currently available to improve prediction.

Few human immunodeficiency virus (HIV)–infected persons can maintain low viral levels without therapeutic intervention. We evaluate predictors of spontaneous control of the viral load (hereafter, “viral control”) in a prospective cohort of African adults shortly after HIV infection. Viral control was defined as ≥2 consecutively measured viral loads (VLs) of ≤10 000 copies/mL after the estimated date of infection, followed by at least 4 subsequent measurements for which the VL in at least 75% was ≤10 000 copies/mL in the absence of ART. Multivariable logistic regression characterized predictors of viral control. Of 590 eligible volunteers, 107 (18.1%) experienced viral control, of whom 25 (4.2%) maintained a VL of 51–2000 copies/mL, and 5 (0.8%) sustained a VL of ≤50 copies/mL. The median ART-free follow-up time was 3.3 years (range, 0.3–9.7 years). Factors independently associated with control were HIV-1 subtype A (reference, subtype C; adjusted odds ratio [aOR], 2.1 [95% confidence interval {CI}, 1.3–3.5]), female sex (reference, male sex; aOR, 1.8 [95% CI, 1.1–2.8]), and having HLA class I variant allele B*57 (reference, not having this allele; aOR, 1.9 [95% CI, 1.0–3.6]) in a multivariable model that also controlled for age at the time of infection and baseline CD4+ T-cell count. We observed strong associations between infecting HIV-1 subtype, HLA type, and sex on viral control in this cohort. HIV-1 subtype is important to consider when testing and designing new therapeutic and prevention technologies, including vaccines., Human immunodeficiency virus type 1 (HIV-1) subtype is important. We show that HIV subtype A is associated with viral control, using subtype C as a reference. Data from this and other studies suggest that HIV-1 subtype should be considered when designing new HIV therapeutic agents, prevention modalities, and vaccines.

IntroductionUnderstanding HIV incidence and risk behaviour among populations being considered for HIV vaccine studies is necessary for the appropriate design of trials.MethodsBetween May 2012 and June 2015, we recruited men aged 18-49 years from urban and peri-urban areas of Rustenburg, a mining town in the North West Province, South Africa. Men who reported HIV-risk behaviour were followed for nine to 12 months to determine HIV incidence and factors associated with condom use.ResultsA total of 400 HIV uninfected men were enrolled; 366 (91.5%) had at least one follow-up visit and were included in the analysis; 47.6% were under 25 years of age. HIV incidence was 1.9 per 100 person-years (95% CI: 0.79-4.56). Among heterosexual men (N = 339), 80.8% reported having vaginal intercourse with multiple partners in the past three months, among whom 74.1% reported inconsistent condom use. Sixty-eight percent reported vaginal intercourse with new female partners, of whom 40.6% reported inconsistent condom use. Over half (55.6%) of men who had sex with men (N = 27) reported anal intercourse with multiple male partners in the past three months, of whom 68.2% reported using condoms inconsistently. Men who had more than two female partners in the last three months (n = 121) were more likely to use condoms inconsistently (aOR 4.31, 95% CI: 1.34-13.8); in contrast, those with more than one new female sex partner (aOR 0.13, 94% CI 0.04-0.44), and whose sexual debut was after 19 years of age (aOR 0.39, 95% CI: 0.15-1.01) were less likely to use condoms inconsistently.ConclusionHIV incidence was low and similar to other studies of heterosexual men in South Africa. To identify men at high risk for HIV for enrolment in prevention trials, future researchers may need to focus on those who report early sexual debut and who report having multiple sexual partners. Men in newer relationships appear to use condoms more frequently.

HIV epidemiology informs prevention trial design and program planning. Nine clinical research centers (CRC) in sub-Saharan Africa conducted HIV observational epidemiology studies in populations at risk for HIV infection as part of an HIV prevention and vaccine trial network. Annual HIV incidence ranged from below 2% to above 10% and varied by CRC and risk group, with rates above 5% observed in Zambian men in an HIV-discordant relationship, Ugandan men from Lake Victoria fishing communities, men who have sex with men, and several cohorts of women. HIV incidence tended to fall after the first three months in the study and over calendar time. Among suspected transmission pairs, 28% of HIV infections were not from the reported partner. Volunteers with high incidence were successfully identified and enrolled into large scale cohort studies. Over a quarter of new cases in couples acquired infection from persons other than the suspected transmitting partner.

INTRODUCTION: Women in HIV prevention trials often must typically agree to avoid pregnancy. Regardless, some become pregnant. Screening tools predicting pregnancy risk could maximize trial safety and efficiency. OBJECTIVES: We assessed incidence and correlates of pregnancy among women at high HIV risk. METHODS: We enrolled sexually-active, HIV-negative women into an observational cohort (2008-2011). At enrollment demographic, contraceptive, reproductive, pregnancy intention and behavioural data were collected. Women reported if one or both partners wanted or intended for the couple to become pregnant. We measured gender role beliefs using a locally validated eight-point index. We tested HIV and pregnancy, and inquired about sexually transmitted infection symptoms (STIs) at enrollment and monthly. HIV testing included behavioural counselling and condom provision, but did not specifically counsel women to avoid pregnancy. Cox proportional hazard modelling evaluated the associations with pregnancy. The multivariate model included the following variables "Recent pregnancy attempts", "Gender Roles Beliefs", "Self-reported STIs" and "Age". RESULTS: We screened 1068 women and excluded (24.6%, 263/1068) who did not report risk behaviour. Non-pregnant, non-sterilized women aged 18-35 (median = 21 years) enrolled (n = 438). Most women reported one partner (74.7%) and a prior live birth (84.6%). Median follow-up time was 6 months (range 0.7-15.5). Pregnancy incidence was 25.1 per 100 women-years (n = 57 pregnancies). Conservative beliefs on gender roles (Adjusted Hazard Ratio (aHR) 1.8; 95% confidence interval [CI] 1.1-2.9), recent pregnancy attempts (aHR 1.9; 95% CI 1.1-3.4) and baseline self-reported STI (aHR 2.5; 95% CI 1.4-4.4) were associated with increased incident pregnancy. Report of no pregnancy intention was associated with lowered pregnancy risk (aHR 0.3; 95% CI 0.1-0.7). CONCLUSIONS: We identified new and confirmed existing factors that can facilitate screening for pregnancy risk.

Background Acute HIV infection (prior to antibody seroconversion) represents a high-risk window for HIV transmission. Development of a test to detect acute infection at the point-of-care is urgent. Methods Volunteers enrolled in a prospective study of HIV incidence in four African cities, Kigali in Rwanda and Ndola, Kitwe and Lusaka in Zambia, were tested regularly for HIV by rapid antibody test and p24 antigen ELISA. Five subgroups of samples were also tested by the Determine Ag/Ab Combo test 1) Antigen positive, antibody negative (acute infection); 2) Antigen positive, antibody positive; 3) Antigen negative, antibody positive; 4) Antigen negative, antibody negative; and 5) Antigen false positive, antibody negative (HIV uninfected). A sixth group included serial dilutions from a p24 antigen-positive control sample. Combo test results were reported as antigen positive, antibody positive, or both. Results Of 34 group 1 samples with VL between 5x105 and >1.5x107 copies/mL (median 3.5x106), 1 (2.9%) was detected by the Combo antigen component, 7 (20.6%) others were positive by the Combo antibody component. No group 2 samples were antigen positive by the Combo test (0/18). Sensitivity of the Combo antigen test was therefore 1.9% (1/52, 95% CI 0.0, 9.9). One false positive Combo antibody result (1/30, 3.3%) was observed in group 4. No false-positive Combo antigen results were observed. The Combo antigen test was positive in group 6 at concentrations of 80 pg/mL, faintly positive at 40 and 20 pg/mL, and negative thereafter. The p24 ELISA antigen test remained positive at 5 pg/mL. Conclusions Although the antibody component of the Combo test detected antibodies to HIV earlier than the comparison antibody tests used, less than 2% of the cases of antigen-positive HIV infection were detected by the Combo antigen component. The development of a rapid point-of-care test to diagnose acute HIV infection remains an urgent goal.

The quest to explain demographic history during the early part of human evolution has been limited because of the scarce paleoanthropological record from the Middle Stone Age. To shed light on the structure of the mitochondrial DNA (mtDNA) phylogeny at the dawn of Homo sapiens, we constructed a matrilineal tree composed of 624 complete mtDNA genomes from sub-Saharan Hg L lineages. We paid particular attention to the Khoi and San (Khoisan) people of South Africa because they are considered to be a unique relic of hunter-gatherer lifestyle and to carry paternal and maternal lineages belonging to the deepest clades known among modern humans. Both the tree phylogeny and coalescence calculations suggest that Khoisan matrilineal ancestry diverged from the rest of the human mtDNA pool 90,000-150,000 years before present (ybp) and that at least five additional, currently extant maternal lineages existed during this period in parallel. Furthermore, we estimate that a minimum of 40 other evolutionarily successful lineages flourished in sub-Saharan Africa during the period of modern human dispersal out of Africa approximately 60,000-70,000 ybp. Only much later, at the beginning of the Late Stone Age, about 40,000 ybp, did introgression of additional lineages occur into the Khoisan mtDNA pool. This process was further accelerated during the recent Bantu expansions. Our results suggest that the early settlement of humans in Africa was already matrilineally structured and involved small, separately evolving isolated populations. S.R. is partially supported by European Union grant MIRG-CT-2007-208019. C.T.S. is supported by The Wellcome Trust. Instituto de Patologia e Imunologia Molecular da Universidade do Porto (IPATIMUP) (L.P.) is supported by Programa Operacional Ciência, Tecnologia e Inovação (POCTI) and Quadro Comunitário de Apoio III.

Background The ability of the Y chromosome to retain a record of its evolution has seen it become an essential tool of molecular anthropology. In the last few years, however, it has also found use in forensic genetics, providing information on the geographic origin of individuals. This has been aided by the development of efficient screening methods and an increased knowledge of geographic distribution. In this study, we describe the development of single base extension assays used to resolve 61 Y chromosome haplogroups, mainly within haplogroups A, B and E, found in Africa. Results Seven multiplex assays, which incorporated 60 Y chromosome markers, were developed. These resolved Y chromosomes to 61 terminal branches of the major African haplogroups A, B and E, while also including a few Eurasian haplogroups found occasionally in African males. Following its validation, the assays were used to screen 683 individuals from Southern Africa, including south eastern Bantu speakers (BAN), Khoe-San (KS) and South African Whites (SAW). Of the 61 haplogroups that the assays collectively resolved, 26 were found in the 683 samples. While haplogroup sharing was common between the BAN and KS, the frequencies of these haplogroups varied appreciably. Both groups showed low levels of assimilation of Eurasian haplogroups and only two individuals in the SAW clearly had Y chromosomes of African ancestry. Conclusions The use of these single base extension assays in screening increased haplogroup resolution and sampling throughput, while saving time and DNA. Their use, together with the screening of short tandem repeat markers would considerably improve resolution, thus refining the geographic ancestry of individuals.