Effect of Universal Testing and Treatment on HIV Incidence - HPTN 071 (PopART)

Abstract

Background: A universal testing and treatment strategy is a potential approach to reduce the incidence of human immunodeficiency virus (HIV) infection, yet previous trial results are inconsistent.

Methods: In the HPTN 071 (PopART) community-randomized trial conducted from 2013 through 2018, we randomly assigned 21 communities in Zambia and South Africa (total population, approximately 1 million) to group A (combination prevention intervention with universal antiretroviral therapy [ART]), group B (the prevention intervention with ART provided according to local guidelines [universal since 2016]), or group C (standard care). The prevention intervention included home-based HIV testing delivered by community workers, who also supported linkage to HIV care and ART adherence. The primary outcome, HIV incidence between months 12 and 36, was measured in a population cohort of approximately 2000 randomly sampled adults (18 to 44 years of age) per community. Viral suppression (<400 copies of HIV RNA per milliliter) was assessed in all HIV-positive participants at 24 months.

Results: The population cohort included 48,301 participants. Baseline HIV prevalence was 21% or 22% in each group. Between months 12 and 36, a total of 553 new HIV infections were observed during 39,702 person-years (1.4 per 100 person-years; women, 1.7; men, 0.8). The adjusted rate ratio for group A as compared with group C was 0.93 (95% confidence interval [CI], 0.74 to 1.18; P = 0.51) and for group B as compared with group C was 0.70 (95% CI, 0.55 to 0.88; P = 0.006). The percentage of HIV-positive participants with viral suppression at 24 months was 71.9% in group A, 67.5% in group B, and 60.2% in group C. The estimated percentage of HIV-positive adults in the community who were receiving ART at 36 months was 81% in group A and 80% in group B.

Conclusions: A combination prevention intervention with ART provided according to local guidelines resulted in a 30% lower incidence of HIV infection than standard care. The lack of effect with universal ART was unanticipated and not consistent with the data on viral suppression. In this trial setting, universal testing and treatment reduced the population-level incidence of HIV infection. (Funded by the National Institute of Allergy and Infectious Diseases and others; HPTN 071 [PopArt] ClinicalTrials.gov number, NCT01900977.).

Figure 1

CONSORT diagram showing enrollment and follow-up of the Population Cohort. HPTN 071 (PopART) included 21 communities that were matched in seven sets of three communities each; the three communities in each triplet were randomized to Study Arms A, B, and C. The purpose of the Population Cohort (PC) was to enrol and follow a representative sample of residents to assess the impact of the PopART intervention on HIV incidence and viral suppression. Participants in the PC were enrolled from randomly selected households in the community; with one member aged 18-44 selected at random for eligibility assessment. The diagram shows the number of participants enrolled at the start of the study (PC0). Additional participants were enrolled in PC12N in communities with fewer than 2000 PC0 participants; additional participants were enrolled in Arms A and C in PC24N to preserve power for this comparison. The status of participants at each survey year (PC12, PC24, PC36) is reported. Individuals who missed yearly follow-up visits were eligible for subsequent annual surveys, individuals who were terminated were not. The percentage retained is the proportion of participants who completed a visit amongst those eligible for the visit.

Figure 2

Estimates of HIV incidence and log ratio-residuals for the seven study triplets. The plots show estimates of HIV incidence (plotted per 100 person-years upper panels) and log ratio-residuals (observed/expected HIV infections adjusted for age, sex and baseline HIV prevalence, lower panels) for Arm A vs. Arm C and Arm B vs. Arm C. Data are shown for the study period included in the primary endpoint analysis (PC12 to PC36). Colored lines represent each of the seven triplets (numbered 1 to 7). For HIV incidence, the size of the colored dot at the end of each line represents the number of events contributing to the incidence estimate for each community. Abbreviations: Z: Zambia; SA: South Africa.

Figure 3

Estimated ART coverage at the end of the study, by age and sex and study arm; estimated from the CHiPs data and extrapolated to total population aged ≥15 years The plot shows estimated ART coverage among the total population aged ≥15 years in Arm A and B communities at the end of the study, by sex, age-group and study arm. Coverage estimates are shown in black solid lines for Arm A and in blue dashed lines for Arm B. Lines for men are shown with a square symbol, and for women with a circle symbol. The UNAIDS 90-90-90 target for ART coverage (81%) is shown in red. The estimated number of HIV-positive men who were resident in the community at the time that CHIPs first visited their household during the third (and last) annual round of intervention, and remained resident in the study community at the end of the study, was 8,388 in Arm A and 8,948 in Arm B, and the estimated number of HIV-positive women was 15,936 in Arm A and 17,586 in Arm B. The estimated number of HIV-positive men on ART was 6,286 in Arm A and 6,378 in Arm B, and the estimated number of HIV-positive women on ART was 13,600 in Arm A and 14,481 in Arm B.