Population-level viremia predicts HIV incidence at the community level across the Universal Testing and Treatment Trials in eastern and southern Africa

Abstract

Universal HIV testing and treatment (UTT) strategies aim to optimize population-level benefits of antiretroviral treatment. Between 2012 and 2018, four large community randomized trials were conducted in eastern and southern Africa. While their results were broadly consistent showing decreased population-level viremia reduces HIV incidence, it remains unclear how much HIV incidence can be reduced by increasing suppression among people living with HIV (PLHIV). We conducted a pooled analysis across the four UTT trials. Leveraging data from 105 communities in five countries, we evaluated the linear relationship between i) population-level viremia (prevalence of non-suppression-defined as plasma HIV RNA >500 or >400 copies/mL-among all adults, irrespective of HIV status) and HIV incidence; and ii) prevalence of non-suppression among PLHIV and HIV incidence, using parametric g-computation. HIV prevalence, measured in 257 929 persons, varied from 2 to 41% across the communities; prevalence of non-suppression among PLHIV, measured in 31 377 persons, from 3 to 70%; population-level viremia, derived from HIV prevalence and non-suppression, from < 1% to 25%; and HIV incidence, measured over 345 844 person-years (PY), from 0.03/100PY to 3.46/100PY. Decreases in population-level viremia were strongly associated with decreased HIV incidence in all trials (between 0.45/100PY and 1.88/100PY decline in HIV incidence per 10 percentage points decline in viremia). Decreases in non-suppression among PLHIV were also associated with decreased HIV incidence in all trials (between 0.06/100PY and 0.17/100PY decline in HIV incidence per 10 percentage points decline in non-suppression). Our results support both the utility of population-level viremia as a predictor of incidence, and thus a tool for targeting prevention interventions, and the ability of UTT approaches to reduce HIV incidence by increasing viral suppression. Implementation of universal HIV testing approaches, coupled with interventions to leverage linkage to treatment, adapted to local contexts, can reduce HIV acquisition at population level.

Fig 1. Simplified causal diagram (directed acyclic graph) for the effect of prevalence of non-suppression among PLHIV on HIV incidence.

In this causal diagram, the effect of prevalence, and thus of population-level viremia on HIV incidence is confounded. In this graph, the effect of non-suppression on HIV incidence is not confounded beyond trial, but adjustment for prevalence, a strong predictor of incidence, is expected to improve precision of estimates.

Fig 2. Relationship at community-level between population-level viremia (the proportion of all adults in the community, both HIV+ and HIV-, with non-suppressed plasma HIV RNA level) and HIV incidence per 100 person-years, by trial.

Each marker represents a community. Lines are based on community-level linear regression.

Fig 3. Cross-gendered relationship at community-level between population-level viremia (the proportion of all adults in the community, both HIV+ and HIV-, with detectable HIV RNA), and HIV incidence per 100 person-years, by trial.

Each marker represents a community. Lines are based on community-level linear regression. Ya Tsie was excluded from this figure as HIV incidence estimates were not available by sex.

Fig 4. Relationship between community-level prevalence of non-suppression among PLHIV and HIV incidence per 100 person-years, by trial.

Each marker represents a community. Lines are based on parametric g-computation to estimate the parameters of a marginal structural model, with adjustment for prevalence in the initial regression step. Under assumptions, the slope of the line reflects the change in expected counterfactual HIV incidence across all communities in a trial per hypothetical unit change in prevalence of non-suppression.