Analytical treatment interruption: detection of an increase in the latent, inducible HIV-1 reservoir more than a decade after viral resuppression

Abstract

AbstractAnalytical treatment interruption (ATI) studies are increasingly being performed to evaluate the efficacy of putative strategies towards HIV-1 reservoir elimination or antiretroviral therapy (ART)-free viral control. A limited number of studies have evaluated the impact of ATI on the HIV-1 reservoir in individuals on suppressive ART. Available data suggests that ATIs have transient impact on the HIV-1 reservoir, mostly measured by levels of total or integrated HIV-1 DNA, in peripheral blood cells prior to ATI and shortly after ART-mediated viral re-suppression. The long-term impact of intervention ATI studies on the latent, inducible HIV-1 reservoir remains uncertain. We report the first clinical study demonstrating an increase in the latent, inducible HIV-1 reservoir, measured by expression of tat/rev multiply spliced RNA, in nine individuals, despite more than a decade of re-suppressive ART, after undergoing an immune intervention ATI conducted in 2006-2009. Our findings challenge the status quo on ATI risk of viral reservoir reseeding and the long-term outcomes thereof.