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J Infect Dis. 2016 Aug 1;214(3):379-89. doi: 10.1093/infdis/jiw093. Epub 2016 Mar 6.

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

Author information

1
Department of Paediatrics.
2
Nuffield Department of Medicine, University of Oxford, United Kingdom.
3
HIV-1 Vaccine Trials Network, Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center.
4
Ragon Institute of MGH, MIT, and Harvard, Cambridge, Massachusetts HIV-1 Pathogenesis Programme, Doris Duke Medical Research Institute, University of KwaZulu-Natal KwaZulu-Natal Research Institute for Tuberculosis and HIV-1, University of KwaZulu-Natal, Durban Max Planck Institute for Infection Biology, Berlin, Germany.
5
Ragon Institute of MGH, MIT, and Harvard, Cambridge, Massachusetts HIV-1 Pathogenesis Programme, Doris Duke Medical Research Institute, University of KwaZulu-Natal.
6
eScience Group, Microsoft Research, Redmond, Washington.
7
South African Medical Research Council, Cape Town Perinatal HIV-1 Research Unit, University of the Witwatersrand, Johannesburg, South Africa.
8
HIV-1 Vaccine Trials Network, Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center Department of Global Health, University of Washington, Seattle.
9
Department of Paediatrics HIV-1 Pathogenesis Programme, Doris Duke Medical Research Institute, University of KwaZulu-Natal.

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/mm(3) (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/10(6) 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.

KEYWORDS:

Gag-specific CD8+ T cells; HIV-1 vaccine; HLA class I; Phambili trial

PMID:
26951820
PMCID:
PMC4936641
DOI:
10.1093/infdis/jiw093
[Indexed for MEDLINE]
Free PMC Article

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