Abstract
Plasma viral load (VL) and CD4+ T cell count are widely used as biomarkers of HIV type 1 (HIV-1) replication, pathogenesis, and response to antiretroviral therapy (ART). However, the clinical potential of cell-associated (CA) HIV-1 molecular markers is much less understood. Here, we measured CA HIV-1 RNA and DNA in HIV-infected individuals treated with temporary ART initiated during primary HIV-1 infection. We demonstrate substantial predictive value of CA RNA for (a) the virological and immunological response to early ART, (b) the magnitude and time to viral rebound after discontinuation of early ART, and (c) disease progression in the absence of treatment. Remarkably, when adjusted for CA RNA, plasma VL no longer appeared as an independent predictor of any clinical endpoint in this cohort. The potential of CA RNA as an HIV-1 clinical marker, in particular as a predictive biomarker of virological control after stopping ART, should be explored in the context of HIV-1 curative interventions.
Highlights
Combination antiretroviral therapy (ART) can successfully manage but is unable to cure HIV type 1 (HIV-1) infection [1]
We have demonstrated substantial predictive value of CA HIV-1 RNA for (a) the virological and immunological response to early ART, (b) the magnitude of and time to viral rebound after early ART discontinuation, and (c) the subsequent disease progression in the absence of treatment
While US RNA was predictive of virological endpoints, such as time to virological suppression on ART, as well as the magnitude of and time to viral rebound after TI, multiply spliced (MS) RNA was not predictive of these endpoints
Summary
Combination antiretroviral therapy (ART) can successfully manage but is unable to cure HIV type 1 (HIV-1) infection [1]. Cell-associated (CA) HIV-1 RNA has been demonstrated to predict ART failure and to correlate with adherence to therapy in virologically suppressed individuals [2, 3], indicating that this marker could be of use in clinical care of individuals on otherwise-suppressive ART because it is more sensitive than plasma VL for associations with certain clinical endpoints. Pre-ART plasma VL, CD4+ T cell count, and total HIV-1 DNA have been shown to predict the rates of virological suppression on ART [4,5,6]. No study has directly compared plasma VL and CA HIV-1 RNA for the prediction of the rate of CD4+ T cell decline in the setting of untreated HIV-1 infection
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