HIV-2 infection as a comparative lens for functional HIV-1 remission

Abstract

is not uniform across studies. Some studies report comparable viral RNA levels between HIV-1 and HIV-2 in CD4-matched individuals. In contrast, others find lower per-cell transcriptional output in HIV-2, suggesting that the degree of transcriptional restriction varies with cohort composition, disease stage, and measurement approach. Importantly, neither finding supports a model of uniform proviral silencing. This review examines the molecular biology, immune responses, and reservoir dynamics of HIV-2 infection, weighing evidence that both supports and challenges the view of HIV-2 as an attenuated comparator to HIV-1. The available data suggest that HIV-2 persistence involves regulated viral expression and ongoing, albeit attenuated, immune engagement, rather than transcriptional silence. However, the extent to which immune activation in HIV-2 is quantitatively or qualitatively distinct from that in HIV-1 remains incompletely resolved. HIV-2 does not provide a prescriptive cure blueprint, but it reveals a key biological constraint: ongoing viral transcription can coexist with prolonged immune containment. This finding argues against transcription-only approaches to HIV-1 remission and underscores the need for strategies that combine transcriptional modulation with sustained immune engagement.