دورية أكاديمية
Lower viral loads and slower CD4 decline in MRKAd5 HIV-1 vaccinees expressing disease-susceptible HLA-B*58:02
| العنوان: | Lower viral loads and slower CD4 decline in MRKAd5 HIV-1 vaccinees expressing disease-susceptible HLA-B*58:02 |
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| المؤلفون: | Leitman, E, Hurst, J, Mori, M, Kublin, J, Ndung'u, T, Walker, B, Carlson, J, Gray, G, Matthews, P, Frahm, N, Goulder, P |
| بيانات النشر: | Oxford University Press |
| سنة النشر: | 2016 |
| المجموعة: | Oxford University Research Archive (ORA) |
| الوصف: | 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.) |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | unknown |
| العلاقة: | https://ora.ox.ac.uk/objects/uuid:06e81c55-11a1-42b9-8bf5-594d9fdc2d03Test; https://doi.org/10.1093/infdis/jiw093Test |
| DOI: | 10.1093/infdis/jiw093 |
| الإتاحة: | https://doi.org/10.1093/infdis/jiw093Test https://ora.ox.ac.uk/objects/uuid:06e81c55-11a1-42b9-8bf5-594d9fdc2d03Test |
| حقوق: | info:eu-repo/semantics/openAccess ; CC Attribution (CC BY) |
| رقم الانضمام: | edsbas.C3D39E71 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1093/infdis/jiw093 |
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