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Lower Viral Loads and Slower CD4+ T-Cell Count Decline in MRKAd5 HIV-1 Vaccinees Expressing Disease-Susceptible HLA-B*58:02.
- Source :
-
The Journal of infectious diseases [J Infect Dis] 2016 Aug 01; Vol. 214 (3), pp. 379-89. Date of Electronic Publication: 2016 Mar 06. - Publication Year :
- 2016
-
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.<br />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.<br />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.<br />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.<br />Clinical Trials Registration: NCT00413725, DOH-27-0207-1539.<br /> (© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America.)
- Subjects :
- Adult
Alleles
CD4 Lymphocyte Count
Enzyme-Linked Immunospot Assay
Female
Humans
Male
Placebos administration & dosage
SAIDS Vaccines administration & dosage
Young Adult
CD4-Positive T-Lymphocytes immunology
CD8-Positive T-Lymphocytes immunology
HIV Infections prevention & control
HIV Infections virology
HLA-B Antigens genetics
SAIDS Vaccines immunology
Viral Load
Subjects
Details
- Language :
- English
- ISSN :
- 1537-6613
- Volume :
- 214
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- The Journal of infectious diseases
- Publication Type :
- Academic Journal
- Accession number :
- 26951820
- Full Text :
- https://doi.org/10.1093/infdis/jiw093