Determination of HIV status and identification of incident HIV infections in a large, community‐randomized trial: HPTN 071 (PopART)

Abstract

Introduction The HPTN 071 (PopART) trial evaluated the impact of an HIV combination prevention package that included “universal testing and treatment” on HIV incidence in 21 communities in Zambia and South Africa during 2013‐2018. The primary study endpoint was based on the results of laboratory‐based HIV testing for> 48,000 participants who were followed for up to three years. This report evaluated the performance of HIV assays and algorithms used to determine HIV status and identify incident HIV infections in HPTN 071, and assessed the impact of errors on HIV incidence estimates. Methods HIV status was determined using a streamlined, algorithmic approach. A single HIV screening test was performed at centralized laboratories in Zambia and South Africa (all participants, all visits). Additional testing was performed at the HPTN Laboratory Center using antigen/antibody screening tests, a discriminatory test and an HIV RNA test. This testing was performed to investigate cases with discordant test results and confirm incident HIV infections. Results HIV testing identified 978 seroconverter cases. This included 28 cases where the participant had acute HIV infection at the first HIV‐positive visit. Investigations of cases with discordant test results identified cases where there was a participant or sample error (mixups). Seroreverter cases (errors where status changed from HIV infected to HIV uninfected, 0.4% of all cases) were excluded from the primary endpoint analysis. Statistical analysis demonstrated that exclusion of those cases improved the accuracy of HIV incidence estimates. Conclusions This report demonstrates that the streamlined, algorithmic approach effectively identified HIV infections in this large cluster‐randomized trial. Longitudinal HIV testing (all participants, all visits) and quality control testing provided useful data on the frequency of errors and provided more accurate data for HIV incidence estimates.

Evaluation of multi-assay algorithms for cross-sectional HIV incidence estimation in settings with universal antiretroviral treatment

“…Participants had up to four annual study visits (PC0, PC12, PC24, and PC36). The samples used in this report were collected 2 years after the start of the trial (at PC24; sample collection 2016–2017) from participants who were living with HIV at the PC24 visit and had known HIV status one year earlier (at PC12) [ 27 ]. Participants who had acute HIV infection at either visit were excluded from analysis.…”

Evaluation of multi-assay algorithms for identifying individuals with recent HIV infection: HPTN 071 (PopART)

“…Most HIV infections in the study countries are HIV subtype C. Samples were collected from participants in the PC at annual visits, referred to as PC0, PC12, PC24, and PC36. HIV status was determined for PC participants at each study visit at the HPTN Laboratory Center [ 34 ]. This report is based on analysis of samples collected at the PC24 visit.…”

HIV drug resistance in a community‐randomized trial of universal testing and treatment: HPTN 071 (PopART)

“…In HPTN 071, key study outcomes were assessed in a population cohort that included a random sample of >48,000 adults aged 18-44 (one per household), reflecting the general adult population. Participants were recruited over the first 2 years of the study and were followed for up to 3 years at annual study visits (at baseline and at the 1-, 2-and 3-year surveys; File S1); HIV testing was performed at each annual visit [12]. Samples analysed in this report were obtained in the 2year survey from PLHIV in the population cohort (collection dates: August 2016-July 2017).…”

“…At the 2‐year survey, the mean community proportion of PLHIV who were virally suppressed (viral load <400 copies/ml) was 71.9% in Arm A, 67.5% in Arm B and 60.2% in Arm C [ 11 ]. The percentage of seroconverters who were virally suppressed at their first HIV‐positive visit increased during the course of the study (25% at 1 year, 30% at 2 years and 33% at 3 years) [ 12 ], suggesting an increase in access to early ART over time.…”