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

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 + IFN γ + and CD8 + Perforin + responses. However, STI was associated with significant decline in breadth of bi-functional (CD8 + IFN γ + Perforin + ) responses; P = .02, Mann-Whitney test. Conclusions . STI in individuals initiated onto ART at <200 CD4 + T-cell counts/ μ l significantly reduced occurrence of bifunctional CD8 + IFN γ + /Perforin + responses. These data add to others that found no evidence to support STI as a strategy to improve HIV-specific immunity during ART.