The size of the expressed HIV reservoir predicts timing of viral rebound after treatment interruption

JZ Li, B Etemad, H Ahmed, E Aga, RJ Bosch… - Aids, 2016 - journals.lww.com
JZ Li, B Etemad, H Ahmed, E Aga, RJ Bosch, JW Mellors, DR Kuritzkes, MM Lederman…
Aids, 2016journals.lww.com
Objectives: Therapies to achieve sustained antiretroviral therapy-free HIV remission will
require validation in analytic treatment interruption (ATI) trials. Identifying biomarkers that
predict time to viral rebound could accelerate the development of such therapeutics. Design:
A pooled analysis of participants from six AIDS Clinical Trials Group ATI studies to identify
predictors of viral rebound. Methods: Cell-associated DNA (CA-DNA) and CA-RNA were
quantified in pre-ATI peripheral blood mononuclear cell samples, and residual plasma …
Abstract
Objectives:
Therapies to achieve sustained antiretroviral therapy-free HIV remission will require validation in analytic treatment interruption (ATI) trials. Identifying biomarkers that predict time to viral rebound could accelerate the development of such therapeutics.
Design:
A pooled analysis of participants from six AIDS Clinical Trials Group ATI studies to identify predictors of viral rebound.
Methods:
Cell-associated DNA (CA-DNA) and CA-RNA were quantified in pre-ATI peripheral blood mononuclear cell samples, and residual plasma viremia was measured using the single-copy assay.
Results:
Participants who initiated antiretroviral therapy (ART) during acute/early HIV infection and those on a non-nucleoside reverse transcriptase inhibitor-containing regimen had significantly delayed viral rebound. Participants who initiated ART during acute/early infection had lower levels of pre-ATI CA-RNA (acute/early vs. chronic-treated: median< 92 vs. 156 HIV-1 RNA copies/10 6 CD4+ cells, P< 0.01). Higher pre-ATI CA-RNA levels were significantly associated with shorter time to viral rebound (≤ 4 vs. 5–8 vs.> 8 weeks: median 182 vs. 107 vs.< 92 HIV-1 RNA copies/10 6 CD4+ cells, Kruskal–Wallis P< 0.01). The proportion of participants with detectable plasma residual viremia prior to ATI was significantly higher among those with shorter time to viral rebound.
Conclusion:
Higher levels of HIV expression while on ART are associated with shorter time to HIV rebound after treatment interruption. Quantification of the active HIV reservoir may provide a biomarker of efficacy for therapies that aim to achieve ART-free HIV remission.
Lippincott Williams & Wilkins