Journal article
Lower viral loads and slower CD4 decline in MRKAd5 HIV-1 vaccinees expressing disease-susceptible HLA-B*58:02
- Abstract:
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Background. 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.
Methods. 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.
Results. 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 CD4andLT;350 cells/mm3 (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/106 PBMC, p=0.06) 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 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.)
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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- Publisher copy:
- 10.1093/infdis/jiw093
Authors
- Publisher:
- Oxford University Press
- Journal:
- Journal of Infectious Diseases More from this journal
- Volume:
- 214
- Issue:
- 3
- Pages:
- 379–389
- Publication date:
- 2016-03-06
- Acceptance date:
- 2016-03-02
- DOI:
- EISSN:
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1537-6613
- ISSN:
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0022-1899
- Keywords:
- Pubs id:
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pubs:614289
- UUID:
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uuid:06e81c55-11a1-42b9-8bf5-594d9fdc2d03
- Local pid:
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pubs:614289
- Source identifiers:
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614289
- Deposit date:
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2016-04-08
- ARK identifier:
Terms of use
- Copyright holder:
- Leitman et al
- Copyright date:
- 2016
- Notes:
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Copyright The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of
America.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License
(http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and
reproduction in any medium, provided the original work is properly cited.
This is the author accepted manuscript following peer review version of the article. The final version is available online from OUP at: https://doi.org/10.1093/infdis/jiw093
- Licence:
- CC Attribution (CC BY)
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