Review: Influence of ART on HIV genetics

Abstract

Purpose of review: 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.

Recent findings: 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.

Summary: 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.

FIGURE 1

Change in HIV plasma RNA and peripheral blood mononuclear cell DNA over 8 years of treatment with ART. Levels of plasma HIV RNA decline in four phases; the last phase has a slope close to zero [–37]. HIV DNA declines initially on ART, but then achieves a steady state at higher levels than HIV RNA [38^■]. When ART is initiated early after infection, diversity is halted and only one or a few variants remain after a long-term treatment [34^■■,39]. When ART is initiated early after infection, diversity is halted and only one or a few variants remain after long-term treatment [34^■■,39,40^■■,41]. ART, antiretroviral therapy; PBMC, peripheral blood mononuclear cells.