Review

Abstract

HIV genetic diversity poses major challenges for the prevention, control, and cure of infection. Characterizing the diversity and evolution of HIV populations within the host provides insights into the mechanisms of HIV persistence during antiretroviral therapy (ART). This review describes the HIV diversity within patients, how it is affected by suppressive ART, and makes a case for early treatment after HIV infection. HIV evolution is effectively halted by ART. However, cells that were infected prior to initiating therapy can proliferate to very high numbers both before and during treatment. Such clonal expansions result in the persistence of integrated proviruses despite therapy. These expanding proviruses have been shown to be a source for residual viremia during ART, and they may be a source for viral rebound after interrupting ART. Plasma HIV RNA shows no evidence for evolution during ART, suggesting that HIV persistence is not driven by low-level, ongoing replication. The emergence of identical viral sequences observed in both HIV RNA and DNA is likely due to proliferation of infected cells. Early treatment restricts the viral population and reduces the number of variants that must be targeted for future therapeutic strategies.