Title | Factors associated with viral rebound in HIV-1-infected individuals enrolled in a therapeutic HIV-1 gag vaccine trial. |
Publication Type | Journal Article |
Year of Publication | 2011 |
Authors | Li JZ, Brumme ZL, Brumme CJ, Wang H, Spritzler J, Robertson MN, Lederman MM, Carrington M, Walker BD, Schooley RT, Kuritzkes DR |
Corporate Authors | AIDS Clinical Trials Group A5197 Study Team |
Journal | J Infect Dis |
Volume | 203 |
Issue | 7 |
Pagination | 976-83 |
Date Published | 2011 Apr 1 |
ISSN | 1537-6613 |
Keywords | Adenoviridae, 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. |
DOI | 10.1093/infdis/jiq143 |
Alternate Journal | J. Infect. Dis. |
PubMed ID | 21402549 |
PubMed Central ID | PMC3068025 |
Grant List | HHSN261200800001E / / 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 |