Abstract
Background. 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.
Highlights
HLA strongly influences human immunodeficiency virus type 1 (HIV-1) disease progression
HLA class I alleles are an important predictor of disease course in human immunodeficiency virus type 1 (HIV-1) infection [1]
In sub-Saharan Africa, HLA-B*57, HLA-B*58:01, and HLAB*81:01 are protective against disease progression, while HLA-B*18:01 and HLA-B*58:02 are associated with rapid progression [2,3,4]
Summary
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. 380 JID 2016:214 (1 August) Leitman et al for whom HLA types, peripheral blood mononuclear cell (PBMC), viral load, and CD4+ T-cell count data were available, compose the focus of this report (Table 1). For the remaining 40 individuals, no PBMC were available to assess CD8+ T-cell responses, and only selected viral load and CD4+ T-cell count data were included in additional analyses; material for HLA typing was available for 25 participants. Subjects were categorized as having protective HLA-B expression (HLA-B*57:02/57:03/58:01/ 81:01); disease-susceptible HLA-B expression (HLA-B*18:01/ 58:02), and neither protective nor disease-susceptible HLA-B expression (eg, HLA-B*42:01/44:03) [2, 3]. All participants provided written informed consent; ethics committee at each clinical site and the University of Oxford approved the study
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