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
View: Text | PDF
Research Article AIDS/HIV Virology

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

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

×

Figure 9

Predictors of disease progression in the absence of treatment.

Options: View larger image (or click on image) Download as PowerPoint
Predictors of disease progression in the absence of treatment. Kaplan-Me...
Kaplan-Meier survival analysis for plasma VL, CA HIV US and MS RNA, total HIV DNA, CD4+ count, and CD4/CD8 ratio, measured at the virological set point (36 weeks after interruption of early ART or randomization), as well as having been treated with early ART or not (n = 56). The composite endpoint of the analysis was either a CD4+ count measurement of less than 350 cells/mm3 or (re)start of ART. Levels of plasma VL, US RNA, MS 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.