Relationship of HIV reservoir characteristics with immune status and viral rebound kinetics in an HIV therapeutic vaccine study.

TitleRelationship of HIV reservoir characteristics with immune status and viral rebound kinetics in an HIV therapeutic vaccine study.
Publication TypeJournal Article
Year of Publication2014
AuthorsLi JZ, Heisey A, Ahmed H, Wang H, Zheng L, Carrington M, Wrin T, Schooley RT, Lederman MM, Kuritzkes DR
Corporate AuthorsACTG A5197 Study Team
JournalAIDS
Volume28
Issue18
Pagination2649-57
Date Published2014 Nov 28
ISSN1473-5571
KeywordsAIDS Vaccines, CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, Cytokines, DNA, Viral, HIV Infections, HIV-1, Humans, Leukocytes, Mononuclear, Placebos, Retrospective Studies, RNA, Viral, Viral Load, Viremia
Abstract

OBJECTIVES: The objective of this study is to evaluate the impact of therapeutic HIV vaccination on the HIV reservoir and assess the relationship of the viral reservoir with HIV-specific immune status and viral rebound kinetics.

DESIGN: A retrospective analysis of ACTG A5197, a randomized, placebo-controlled trial of a therapeutic rAd5 HIV-1 gag vaccine.

METHODS: Participants received vaccine/placebo at weeks 0, 4 and 26 prior to a 16-week analytic treatment interruption (ATI) at week 38. Cell-associated HIV-1 RNA and DNA (CA-RNA and CA-DNA) and HIV-1 residual viremia were quantified at weeks 0, 8 and 38. HIV-specific CD4(+)/CD8(+) activity was assessed by an intracellular cytokine staining assay.

RESULTS: At study entry, CA-RNA and CA-DNA levels were correlated inversely with the numbers of HIV-specific CD4(+) interferon-γ producing cells (CA-RNA: r = -0.23, P = 0.03 and CA-DNA: r = -0.28, P < 0.01, N = 93). Therapeutic HIV vaccination induced HIV-specific CD4(+) activity, but did not significantly affect levels of CA-RNA or CA-DNA. Vaccine recipients with undetectable residual viremia at week 8 had higher frequencies of HIV-specific CD4(+) and CD8(+) interferon-γ producing cells (undetectable versus detectable residual viremia: 277 versus 161 CD4(+) cells/10(6) lymphocytes, P = 0.03 and 1326 versus 669 CD8(+) cells/10 lymphocytes, P = 0.04). Pre-ATI CA-RNA and CA-DNA were associated with post-ATI plasma HIV set point (CA-RNA: r = 0.51, P < 0.01 and CA-DNA: r = 0.47, P < 0.01).

CONCLUSION: Vaccine-induced T-cell responses were associated with a modest transient effect on residual viremia, but more potent immune responses and/or combination treatment with latency-reversing agents are needed to reduce the HIV reservoir. HIV reservoir measures may act as biomarkers of post-ATI viral rebound kinetics.

CLINICAL TRIALS REGISTRATION: NCT00080106.

DOI10.1097/QAD.0000000000000478
Alternate JournalAIDS
PubMed ID25254301
PubMed Central IDPMC4267919
Grant List5P30AI060354-08 / AI / NIAID NIH HHS / United States
P30 AI060354 / AI / NIAID NIH HHS / United States
UL1 TR000042 / TR / NCATS 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
UM1 AI106701 / AI / NIAID NIH HHS / United States