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

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.

Figures

Figure 1.

Association between ATI week 16 virus load endpoint (log10 HIV-1 RNA copies/mL) and the number of amino acid mismatches between vaccine and subject Gag sequences in the vaccine (A) and placebo (B) arms.

Figure 2.

Number of HLA-associated Gag escape mutations (A) and proportion of HLA-associated Gag polymorphic sites showing escape mutations (B) per person by HLA group. The proportion of escape mutations was calculated as the number of HLA-associated polymorphisms in a viral sequence divided by the total number of possible HLA-associated polymorphic sites for each subject.