The impact of acute stress on the HIV reservoir: a prospective interventional trial

The persistence of latently infected CD4⁺ T cells is the major barrier to cure of people with HIV (PWH) on antiretroviral therapy (ART). While most latently infected cells are transcriptionally silent, some express low levels of cell associated (CA) HIV RNA. In this prospective controlled interventional study, we tested the hypothesis that acute psychological stress could drive HIV transcription in PWH on ART. PWH on suppressive ART underwent the Trier Social Stress Test (TSST) and comparisons were made to a similar period of time without an intervention (control). During the test, physiological markers of acute psychological stress including pre-ejection period and cardiac output changed in all participants, as anticipated. Compared to the control day, the TSST led to a significant increase in CA HIV RNA with no change in the level of cell associated HIV DNA, indicating an increase in HIV transcription in response to stress. Change in HIV transcription was associated with physiological markers of stress but not with changes in immune cells. These data demonstrate that HIV transcription is increased following acute stress and have implications on the impact of stress on the HIV reservoir and the design of cure strategies for PWH.