CD8+T-Cell Responses before and after Structured Treatment Interruption in Ugandan Adults Who Initiated ART with CD4+T Cells <200 Cell/μL: The DART Trial STI Substudy

Abstract

Objective. To better understand attributes of ART-associated HIV-induced T-cell responses that might be therapeutically harnessed.Methods. CD8+T-cell responses were evaluated in some HIV-1 chronically infected participants of the fixed duration STI substudy of the DART trial. Magnitudes, breadths, and functionality of IFN-γ and Perforin responses were compared in STI (n=42) and continuous treatment (CT) (n=46) before and after a single STI cycle when the DART STI trial was stopped early due to inferior clinical outcome in STI participants.Results. STI and CT had comparable magnitudes and breadths of monofunctional CD8+IFNγ+and CD8+Perforin+responses. However, STI was associated with significant decline in breadth of bi-functional (CD8+IFNγ+Perforin+) responses;P=.02, Mann-Whitney test.Conclusions. STI in individuals initiated onto ART at <200 CD4+T-cell counts/μl significantly reduced occurrence of bifunctional CD8+IFNγ+/Perforin+responses. These data add to others that found no evidence to support STI as a strategy to improve HIV-specific immunity during ART.