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Cell-associated HIV-1 RNA predicts viral rebound and disease progression after discontinuation of temporary early ART
Alexander O. Pasternak, Marlous L. Grijsen, Ferdinand W. Wit, Margreet Bakker, Suzanne Jurriaans, Jan M. Prins, Ben Berkhout
Alexander O. Pasternak, Marlous L. Grijsen, Ferdinand W. Wit, Margreet Bakker, Suzanne Jurriaans, Jan M. Prins, Ben Berkhout
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Research Article AIDS/HIV Virology

Cell-associated HIV-1 RNA predicts viral rebound and disease progression after discontinuation of temporary early ART

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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.

Authors

Alexander O. Pasternak, Marlous L. Grijsen, Ferdinand W. Wit, Margreet Bakker, Suzanne Jurriaans, Jan M. Prins, Ben Berkhout

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Figure 7

On-ART predictors of time to viral rebound after interruption of early ART.

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On-ART predictors of time to viral rebound after interruption of early A...
Kaplan-Meier survival analysis for CA HIV US RNA, total HIV DNA, CD4+ count, and CD4/CD8 ratio, measured at the latest time point available before interruption of early ART, as well as detectability of CA HIV MS RNA at any time point on early ART, and time on early ART (60 or 24 weeks) (n = 51). The endpoint of the analysis was viral rebound to more than 50 or more than 400 copies/mL. Levels of US RNA, total HIV DNA, CD4+ count, and CD4/CD8 ratio were stratified into “high” and “low” strata based on median values. HRs and 95% CIs were calculated using Mantel-Haenszel method. P values were calculated using log-rank tests. det, detectable; ud, undetectable.

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