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

TitleThe size of the expressed HIV reservoir predicts timing of viral rebound after treatment interruption.
Publication TypeJournal Article
Year of Publication2016
AuthorsLi JZ, Etemad B, Ahmed H, Aga E, Bosch RJ, Mellors JW, Kuritzkes DR, Lederman MM, Para M, Gandhi RT
JournalAIDS
Volume30
Issue3
Pagination343-53
Date Published2016 Jan 28
ISSN1473-5571
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 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 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.

DOI10.1097/QAD.0000000000000953
Alternate JournalAIDS
PubMed ID26588174
PubMed Central IDPMC4840470
Grant List5P30AI060354-08 / AI / NIAID NIH HHS / United States
AI100699 / AI / NIAID NIH HHS / United States
AI36219 / AI / NIAID NIH HHS / United States
K08 AI100699 / AI / NIAID NIH HHS / United States
R21 AI114448 / AI / NIAID NIH HHS / United States
UM1 AI068634 / AI / NIAID NIH HHS / United States
UM1 AI068634 / AI / NIAID NIH HHS / United States
UM1 AI068636 / AI / NIAID NIH HHS / United States
UM1 AI068636 / AI / NIAID NIH HHS / United States