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

Leitman, Ellen M.Hurst, JacobMori, MasahikoKublin, JamesNdung'u, ThumbiWalker, BruceCarlson, JonathanGray, Glenda E.Matthews, Philippa C.Frahm, NicoleGoulder, Philip J.R.2016-08-092016Leitman, E. M., J. Hurst, M. Mori, J. Kublin, T. Ndung'u, B. D. Walker, J. Carlson, et al. 2016. “Lower Viral Loads and Slower CD4+ T-Cell Count Decline in MRKAd5 HIV-1 Vaccinees Expressing Disease-Susceptible HLA-B*58:02.” The Journal of Infectious Diseases 214 (3): 379-389. doi:10.1093/infdis/jiw093. http://dx.doi.org/10.1093/infdis/jiw093.0022-1899http://nrs.harvard.edu/urn-3:HUL.InstRepos:27822402Background. HLA strongly influences human immunodeficiency virus type 1 (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. Methods. Viral loads, CD4+ T-cell counts, and enzyme-linked immunospot assay–determined anti-HIV-1 CD8+ T-cell responses for a subset of infected antiretroviral-naive Phambili participants, selected according to sample availability, were analyzed. Results. Among those expressing disease-susceptible HLA-B*58:02, vaccinees had a lower chronic viral set point than placebo recipients (median, 7240 vs 122 500 copies/mL; P = .01), a 0.76 log10 lower longitudinal viremia level (P = .01), and slower progression to a CD4+ T-cell count of <350 cells/mm3 (P = .02). These differences were accompanied by a higher Gag-specific breadth (4.5 vs 1 responses; P = .04) and magnitude (2300 vs 70 spot-forming cells/106 peripheral blood mononuclear cells; P = .06) in vaccinees versus placebo recipients. Conclusions. In addition to the known enhancement of HIV-1 acquisition resulting from the MRKAd5 HIV-1 vaccine, these findings in a nonrandomized subset of enrollees show an HLA-specific vaccine effect on the time to CD4+ T-cell count decline and viremia level after infection and the potential for vaccines to differentially alter disease outcome according to population HLA composition. Clinical Trials Registration. NCT00413725, DOH-27-0207-1539.en-USHLA class IHIV-1 vaccinePhambili trialGag-specific CD8+ T cellsLower Viral Loads and Slower CD4+ T-Cell Count Decline in MRKAd5 HIV-1 Vaccinees Expressing Disease-Susceptible HLA-B*58:02Journal Article2016-08-0910.1093/infdis/jiw093