HIV Proviral DNA: Clinical Applications, Drug Resistance, and the HIV Reservoir

Abstract

Abstract: Antiretroviral therapy has rendered HIV a manageable chronic infection, but integrated proviral DNA within long-lived CD4+ memory T cells persists indefinitely and constitutes both a barrier to cure and an archive of the patient’s virologic history. Genotypic resistance testing performed on proviral DNA from peripheral blood mononuclear cells can recover drug resistance mutations no longer detectable in plasma, characterize viral subtype, and provide an estimate of reservoir burden. This narrative review summarizes the biology of the proviral reservoir, compares Sanger and next-generation sequencing platforms, and addresses interpretive pitfalls including APOBEC3-mediated G-to-A hypermutation and the predominance of replication-defective proviruses. The clinical weight of an archived mutation varies by antiretroviral class, tracking inversely with genetic barrier. The CD4/CD8 ratio is discussed as an accessible correlate of reservoir burden and immune dysregulation. Judicious use requires clear articulation of how a result will alter management.