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Cell-associated HIV-1 RNA predicts viral rebound and disease progression after discontinuation of temporary early ART
Alexander O. Pasternak, … , Jan M. Prins, Ben Berkhout
Alexander O. Pasternak, … , Jan M. Prins, Ben Berkhout
Published February 25, 2020
Citation Information: JCI Insight. 2020;5(6):e134196. https://doi.org/10.1172/jci.insight.134196.
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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 6

Predictors of magnitude of viral rebound after interruption of early ART.

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Predictors of magnitude of viral rebound after interruption of early ART...
(A and B) Coefficient plots of variables measured (A) at early ART interruption (n = 51) or (B and C) at the start of early ART (baseline) (n = 43). Effect sizes and 95% CIs for the associations of the variables with plasma VL at the virological set point were calculated by fitting univariable and multivariable generalized linear models. For baseline, 2 models are shown, including either US RNA and total HIV-1 DNA separately (model I, B) or the US RNA/total DNA ratio as a single variable (model II, C). US RNA/total DNA ratio was calculated taking into account that 106 PBMCs contain 1 μg of total RNA (74). (D) The final multivariable model. Units of measurement of total HIV-1 DNA are log10 copies/106 PBMCs and of US are log10 copies/μg total RNA. Significant associations are marked in red.

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