Validation of population-level HIV-1 incidence estimation by cross-sectional incidence assays in the HPTN 071 (PopART) trial

Abstract

Introduction: Cross-sectional incidence testing is used to estimate population-level HIV incidence and measure the impact of prevention interventions. There are limited data evaluating the accuracy of estimates in settings where antiretroviral therapy coverage and levels of viral suppression are high. Understanding cross-sectional incidence estimates in these settings is important as viral suppression can lead to false recent test results. We compared the accuracy of multi-assay algorithms (MAA) for incidence estimation to that observed in the community-randomized HPTN 071 (PopART) trial, where the majority of participants with HIV infection were virally suppressed.

Methods: HIV incidence was assessed during the second year of the study, and included only individuals who were tested for HIV at visits 1 and 2 years after the start of the study (2016-2017). Incidence estimates from three MAAs were compared to the observed incidence between years 1 and 2 (MAA-C: LAg-Avidity <2.8 ODn + BioRad Avidity Index <95% + VL >400 copies/ml; LAg+VL MAA: LAg-Avidity <1.5 ODn + VL >1000 copies/ml; Rapid+VL MAA: Asanté recent rapid result + VL >1000 copies/ml). The mean duration of recent infection (MDRI) used for the three MAAs was 248, 130 and 180 days, respectively.

Results and discussion: The study consisted of: 15,845 HIV-negative individuals; 4406 HIV positive at both visits; and 221 who seroconverted between visits. Viral load (VL) data were available for all HIV-positive participants at the 2-year visit. Sixty four (29%) of the seroconverters and 3227 (72%) prevelant positive participants were virally supressed (<400 copies/ml). Observed HIV incidence was 1.34% (95% CI: 1.17-1.53). Estimates of incidence were similar to observed incidence for MAA-C, 1.26% (95% CI: 1.02-1.51) and the LAg+VL MAA, 1.29 (95% CI: 0.97-1.62). Incidence estimated by the Rapid+VL MAA was significantly lower than observed incidence (0.92%, 95% CI: 0.69-1.15, p<0.01).

Conclusions: MAA-C and the LAg+VL MAA provided accurate point estimates of incidence in this cohort with high levels of viral suppression. The Rapid+VL significantly underestimated incidence, suggesting that the MDRI recommended by the manufacturer is too long or the assay is not accurately detecting enough recent infections.

Keywords: HPTN; PopART; cross-sectional incidence estimation; multi-assay algorithm; sub-Saharan Africa; validation study.

Figure 1

Comparison of cross‐sectional incidence estimates to observed incidence in HPTN 071 (PopART). The figure shows a comparison of annual HIV incidence observed in the HPTN 071 (PopART) trial, and incidence estimated with three multi‐assay algorithms (MAAs). Abbreviations: LAg, limiting antigen avidity assay; MAA‐C, Clade C multi‐assay algorithm; Rapid, Asante rapid LAg test assay; VL, viral load.

Figure 2

Comparison of cross‐sectional incidence estimates to observed incidence in HPTN 071 (PopART) by study arm, country, sex and sex among young persons. The plots show observed incidence and incidence estimates for three multi‐assay algorithms (MAAs). The circles represent observed incidence based on longitudinal follow‐up. The sub‐analyses are presented by study arm (a); country (b); sex (c); and sex among young (aged 18–24) individuals (d); 95% confidence intervals are shown for each point estimate of incidence. Incidence estimates that differ significantly from the observed incidence are noted (* p<0.05; ** p<0.01). Abbreviations: LAg, limiting antigen avidity assay; MAA‐C, Clade C optimized multi‐assay algorithm; Rapid, Asante rapid LAg test assay; VL, viral load.