Lower Viral Loads and Slower CD4+ T-Cell Count Decline in MRKAd5 HIV-1 Vaccinees Expressing Disease-Susceptible HLA-B*58:02

Ellen M. Leitman, Jacob Hurst, Masahiko Mori, James Kublin, Thumbi Ndung'u, Bruce D. Walker, Jonathan Carlson, Glenda E. Gray, Philippa C. Matthews, Nicole Frahm, Philip J.R. Goulder

 HLA strongly influences HIV-1 disease progression. A major contributory mechanism is via the particular HLA-presented HIV-1 epitopes that are recognized by CD8+ T-cells. Different populations vary considerably in the HLA alleles expressed. We investigated the HLA-specific impact of the MRKAd5 HIV-1 Gag/Pol/Nef vaccine in a subset of the infected Phambili cohort in whom the disease-susceptible HLA-B*58:02 is highly prevalent.  Viral loads, CD4 counts and ELISPOT anti-HIV-1 CD8+ T-cell responses for a subset of infected ART-naïve Phambili participants, selected according to sample availability, were analyzed.  Among those expressing disease-susceptible HLA-B*58:02, vaccinees had a lower chronic viral setpoint than placebo-recipients (median 7,240 versus 122,500 copies/ml, p=0.01), a 0.76log10 lower longitudinal viremia (p=0.01), and slower progression to CD4<350 cells/mm(3) (p=0.02). These differences were accompanied by higher Gag-specific breadth (4.5 versus 1 responses, p=0.04) and magnitude (2,300 versus 70 SFC/10(6) PBMC, p=0.06) in vaccinees versus placebo-recipients.  In addition to the known enhancement of HIV-1 acquisition resulting from the MRKAd5 HIV-1 vaccine, these findings in a non-randomized subset of enrolees show an HLA-specific vaccine effect on time to CD4 decline and viremia post-infection and the potential for vaccines to differentially alter disease outcome according to population HLA composition. (Registration: NCT00413725, DOH-27-0207-1539.).