Background Universal testing and treatment (UTT) is a potential strategy to reduce HIV incidence, yet prior trial results are inconsistent. We report results from HPTN 071 (PopART), the largest HIV prevention trial to date. Methods In this community-randomized trial (2013-18), 21 communities in Zambia and South Africa were randomized to Arm A (PopART intervention, universal antiretroviral therapy [ART]), Arm B (PopART intervention, ART per local guidelines), and Arm C (standard-of-care). The PopART intervention included home-based HIV-testing delivered by community workers who supported linkage-to-care, ART adherence, and other services. The primary outcome, HIV incidence between months 12-36, was measured in a Population Cohort (PC) of ~2,000 randomly-sampled adults/community aged 18-44y. Viral suppression (VS, <400 copies HIV RNA/ml) was measured in all HIV-positive PC participants at 24m. Results The PC included 48,301 participants. Baseline HIV prevalence was similar across study arms (21%-22%). Between months 12-36, 553 incident HIV infections were observed over 39,702 person-years (py; 1.4/100py; women: 1.7/100py; men: 0.8/100py). Adjusted rate-ratios were A vs. C: 0.93 (95%CI: 0.74-1.18, p=0.51); B vs. C: 0.70 (95%CI: 0.55-0.88, p=0.006). At 24m, VS was 71.9% in Arm A; 67.5% in Arm B; and 60.2% in Arm C. ART coverage after 36m was 81% in Arm A and 80% in Arm B. Conclusions The PopART intervention with ART per local guidelines reduced HIV incidence by 30%. The lack of effect with universal ART was surprising and inconsistent with VS data. This study provides evidence that UTT can reduce HIV incidence at population level. Trial registration ClinicalTrials.gov NCT01900977

We combined two tuberculosis (TB) genome-wide association studies (GWAS) from Ghana and The Gambia with subsequent replication totalling 11,425 participants. A significant association with disease was observed at SNP rs4331426 located in a gene-poor region on chromosome 18q11.2 (P=6.8×10−9, OR=1.19, 95%CI=1.13-1.27). Our finding shows that GWAS can identify novel loci for infectious causes of mortality even in Africa where levels of linkage disequilibrium are particularly low.

BackgroundEffective interventions to reduce HIV incidence in sub-Saharan Africa are urgently needed. Mathematical modelling and the HIV Prevention Trials Network (HPTN) 052 trial results suggest that universal HIV testing combined with immediate antiretroviral treatment (ART) should substantially reduce incidence and may eliminate HIV as a public health problem. We describe the rationale and design of a trial to evaluate this hypothesis.Methods/DesignA rigorously-designed trial of universal testing and treatment (UTT) interventions is needed because: i) it is unknown whether these interventions can be delivered to scale with adequate uptake; ii) there are many uncertainties in the models such that the population-level impact of these interventions is unknown; and ii) there are potential adverse effects including sexual risk disinhibition, HIV-related stigma, over-burdening of health systems, poor adherence, toxicity, and drug resistance.In the HPTN 071 (PopART) trial, 21 communities in Zambia and South Africa (total population 1.2 m) will be randomly allocated to three arms. Arm A will receive the full PopART combination HIV prevention package including annual home-based HIV testing, promotion of medical male circumcision for HIV-negative men, and offer of immediate ART for those testing HIV-positive; Arm B will receive the full package except that ART initiation will follow current national guidelines; Arm C will receive standard of care. A Population Cohort of 2,500 adults will be randomly selected in each community and followed for 3 years to measure the primary outcome of HIV incidence. Based on model projections, the trial will be well-powered to detect predicted effects on HIV incidence and secondary outcomes.DiscussionTrial results, combined with modelling and cost data, will provide short-term and long-term estimates of cost-effectiveness of UTT interventions. Importantly, the three-arm design will enable assessment of how much could be achieved by optimal delivery of current policies and the costs and benefits of extending this to UTT.Trial registrationClinicalTrials.gov NCT01900977.

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