Opportunities and Challenges in HIV Treatment as Prevention Research: Results from the ANRS 12249 Cluster-Randomized Trial and Associated Population Cohort.

purpose of reviewThe ANRS 12249 treatment as prevention (TasP) trial investigated the impact of a universal test and treat (UTT) approach on reducing HIV incidence in one of the regions of the world most severely affected by the HIV epidemic-KwaZulu-Natal, South Africa. We summarize key findings from this trial as well as recent findings from controlled studies conducted in the linked population cohort quantifying the long-term effects of expanding ART on directly measured HIV incidence (2004-2017). RECENT

findingsThe ANRS TasP trial did not-and could not-demonstrate a reduction in HIV incidence, because the offer of UTT in the intervention communities did not increase ART coverage and population viral suppression compared to the standard of care in the control communities. Ten controlled studies from the linked population cohort-including several quasi-experimental study designs-exploit heterogeneity in ART exposure to show a consistent and substantial impact of expanding provision of ART and population viral suppression on reduction in HIV incidence at the couple, household, community, and population levels. In this setting, all of the evidence from large, population-based studies (inclusive of the ANRS TasP trial) is remarkably coherent and consistent-i.e., higher ART coverage and population viral suppression were repeatedly associated with clear, measurable decreases in HIV incidence. Thus, the expanded provision of ART has plausibly contributed in a major way toward the dramatic 43% decline in population-level HIV incidence in this typical rural African population. The outcome of the ANRS TasP trial constitutes a powerful null finding with important insights for overcoming implementation challenges in the population delivery of ART. This finding does not imply lack of ART effectiveness in blocking onward transmission of HIV nor its inability to reduce HIV incidence. Rather, it demonstrates that large increases in ART coverage over current levels will require health systems innovations to attract people living with HIV in early stages of the disease to participate in HIV treatment. Such innovations and new approaches are required for the true potential of UTT to be realized.