Population-level Viremia Predicts HIV Incidence across the Universal Test and Treat Studies - Petersen, Maya; Larmarange, Joseph; Wirth, Kathleen E; Skalland, Timothy; Ayles, Helen; Kamya, Moses; Lockman, Shahin; Iwuji, Collins; Dabis, François; Makhema, Joseph; Havlir, Diane; Floyd, Sian; et al.
Improved understanding of the extent to which increased population-level viral suppression will reduce HIV incidence is needed. Using data from four large Universal Test and Treat Trials, we evaluated the relationship between viremia and incidence and its consistency across epidemic contexts. We analyzed data from 105 communities in the PopART (21 communities in South Africa and Zambia, ~ 25,000 adults each), BCPP (30 communities in Botswana, ~3,600 adults each), ANRS 12249 TasP (22 communities in South Africa, ~1,300 adults each) and SEARCH (32 communities in Uganda and Kenya, ~5,000 adults each) studies. Communities ranged from rural to urban and varied in the mobility of their populations and their sex ratio (~30% to 50% male). HIV incidence was measured via repeat testing between 2012-2018. Population viremia – % of all adults (HIV+ or HIV-) with HIV viremia – was estimated at midpoint of follow-up based on HIV prevalence and non-suppression among HIV+, with adjustment for differences between the measurement cohort and underlying population. Community-level regression, adjusted for study, was used to quantify the association between HIV incidence and viremia and to evaluate cross-study heterogeneity. HIV prevalence (measured in 257,929 total persons, PopART: 37,006; BCPP: 12,570; TasP: 20,978; SEARCH: 187,375), ranged from 2% to 40% by community. Non-suppression among HIV+ (measured in 39,928 persons, PopART: 6,233; BCPP: 2,318; TasP: 6,617; SEARCH: 16,209) ranged from 3% to 70%. HIV incidence (measured over 345,844 person-years, PopART: 39,702; BCPP: 8,551; TasP: 26,832; SEARCH: 270,759) ranged from 0.03 to 3.4 per 100PY. Population-level viremia was strongly associated with HIV incidence; pooling across studies, HIV incidence decreased by 0.07/100PY (95% CI: 0.05,0.10, p<0.001) for each 1% absolute decrease in viremia. Incidence was significantly associated with viremia in each study; however, both strength of the incidence-viremia relationship (slope) and projected incidence at 0% viremia (intercept) differed (Figure). Lower population-level HIV viremia was associated with lower HIV incidence in all four Universal Test and Treat Studies, conducted in a wide range of epidemic contexts in sub-Saharan Africa. Differences in external infection rate (due to variation in community size, mobility, and sex ratio) may have contributed to heterogeneity between studies.
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