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The identical viral sequences observed for many years in both the plasma and infected cells of patients on long-term ART are likely due to the proliferation of infected cells both prior to and during treatment. Such cells may also be the source for viral rebound after interrupting ART. Some expanded cell clones carry intact and replication-competent proviruses with a small fraction of the clonal siblings being transcriptionally active and a source for residual viremia on ART.

It also describes how CD4+ T cells that were likely infected with latent proviruses prior to initiating treatment can proliferate before and during ART, providing a renewable source of infected cells despite therapy. This review describes common methods used to obtain and analyze intra-patient HIV sequence data, the accumulation of diversity prior to ART and how it is affected by suppressive ART, the debate on viral replication and evolution in the presence of ART, HIV compartmentalization across various tissues, and mechanisms for the emergence of drug resistance. Characterizing HIV genetic diversity and evolution during antiretroviral therapy (ART) provides insights into the mechanisms that maintain the viral reservoir during ART.