Factors associated with viral rebound in HIV-1-infected individuals enrolled in a therapeutic HIV-1 gag vaccine trial.

TitleFactors associated with viral rebound in HIV-1-infected individuals enrolled in a therapeutic HIV-1 gag vaccine trial.
Publication TypeJournal Article
Year of Publication2011
AuthorsLi JZ, Brumme ZL, Brumme CJ, Wang H, Spritzler J, Robertson MN, Lederman MM, Carrington M, Walker BD, Schooley RT, Kuritzkes DR
Corporate AuthorsAIDS Clinical Trials Group A5197 Study Team
JournalJ Infect Dis
Volume203
Issue7
Pagination976-83
Date Published2011 Apr 1
ISSN1537-6613
KeywordsAdenoviridae, AIDS Vaccines, Drug Carriers, gag Gene Products, Human Immunodeficiency Virus, Genetic Vectors, HIV Infections, HIV-1, HLA Antigens, Humans, Immunotherapy, Placebos, Plasma, pol Gene Products, Human Immunodeficiency Virus, RNA, Viral, Treatment Outcome, Vaccination, Viral Load
Abstract

BACKGROUND: Human immunodeficiency virus type 1 (HIV-1) vaccines directed to the cell-mediated immune system could have a role in lowering the plasma HIV-1 RNA set point, which may reduce infectivity and delay disease progression.

METHODS: Randomized, placebo-controlled trial involving HIV-1-infected participants who received a recombinant adenovirus serotype 5 (rAd5) HIV-1 gag vaccine or placebo. Sequence-based HLA typing was performed for all 110 participants who initiated analytic treatment interruption (ATI) to assess the role of HLA types previously associated with HIV prognosis. Plasma HIV-1 gag and pol RNA sequences were obtained during the ATI. Virologic endpoints and HLA groups were compared between treatment arms using the 2-sample rank sum test. A linear regression model was fitted to derive independent correlates of ATI week 16 plasma viral load (w16 PVL).

RESULTS: Vaccinated participants with neutral HLA alleles had lower median w16 PVLs than did vaccinated participants with protective HLA alleles (P = .01) or placebo participants with neutral HLA alleles (P = .02). Factors independently associated with lower w16 PVL included lower pre-antiretroviral therapy PVL, greater Gag sequence divergence from the vaccine sequence, decreased proportion of HLA-associated polymorphisms in Gag, and randomization to the vaccine arm.

CONCLUSIONS: Therapeutic vaccination with a rAd5-HIV gag vaccine was associated with lower ATI week 16 PVL even after controlling for viral and host genetic factors.

CLINICAL TRIALS REGISTRATION: NCT00080106.

DOI10.1093/infdis/jiq143
Alternate JournalJ. Infect. Dis.
PubMed ID21402549
PubMed Central IDPMC3068025
Grant ListHHSN261200800001E / / PHS HHS / United States
K24 RR016482 / RR / NCRR NIH HHS / United States
P30 AI060354 / AI / NIAID NIH HHS / United States
P30 AI60354 / AI / NIAID NIH HHS / United States
T32 AI007387 / AI / NIAID NIH HHS / United States
T32 AI07387 / AI / NIAID NIH HHS / United States
U01 AI068634 / AI / NIAID NIH HHS / United States
U01 AI068636 / AI / NIAID NIH HHS / United States
/ / Canadian Institutes of Health Research / Canada
/ / Intramural NIH HHS / United States