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A combination strategy for the prevention of human immunodeficiency virus (HIV) is defined as the concurrent implementation of multiple interventions to reduce the incidence of HIV infection.1 Most prevention packages in sub-Saharan Africa include antiretroviral therapy (ART) and medical male circumcision, along with provision of HIV testing and counseling, promotion of condom use, and other behavioral interventions.2 The scale-up of such a combination strategy for HIV prevention has been an intense focus in the field of global health over the past decade.3
Modeling studies indicate that high coverage of ART and male circumcision could substantially reduce the incidence of HIV infection to low-endemic levels,4,5 and could potentially even lead to its elimination.6,7 However, the effectiveness of combination strategies for HIV prevention remains uncertain owing to challenges in increasing coverage of interventions and in accurately measuring changes in the population-level incidence of HIV infection.8,9 Providing evidence of the population-level effectiveness of HIV prevention efforts is critical to understanding whether the current evidence-based interventions are sufficient to mitigate HIV infection and to guide allocation of resources.
Although previous research from South Africa has shown that increasing community ART coverage reduces individual-level risk of HIV infection, declines in the incidence of population-level HIV infection were not shown.10,11 Other research from North America suggests that scale-up of ART has reduced the incidence of HIV infection, but these studies relied on modeled incidence and sentinel surveillance data.9,12–14 The standard empirical method for assessing the incidence of HIV infection is the longitudinal measurement of HIV seroconversions in a population-based cohort.8,9 However, such studies are rare despite the urgency to show relationships between changes in coverage of ART and male circumcision and the incidence of HIV infection over time.4,5,15 To assess the effect of a combination strategy for HIV prevention on the incidence of HIV infection, we analyzed long-term trends in HIV incidence in Rakai, Uganda, on the basis of observed seroconversions and their associations with the scale-up of ART and male circumcision, population-level viral-load suppression, and sexual behaviors. Here, the combination strategy that was assessed included HIV counseling and testing, voluntary medical...