P24.12
Background: The mechanisms of viral control in HIV-1 infected long-term non-progressors (LTNP) may be informative in vaccine design or other biomedical interventional strategies. Host HLA class I alleles restrict virus-specific CD8+ T cells and have been shown to play a key role in HIV control. In this study, we characterized HLA class I profiles and CD8+ T cell responses in LTNP women from Kigali, Rwanda to explore immunological basis of viral control.
Methods: Twenty-one females recruited with HIV-1 infection in the late 1980s in Kigali, Rwanda were longitudinally followed. Nineteen of these women remain therapy naïve, not meeting the national guidelines for combination antiretroviral therapy, and were classified as LTNP. Viral loads, CD4 counts and HLA typing were performed by standard methods. HIV-specific CD8+ T cells were enumerated by IFN-γ ELISPOT assays using PBMC and overlapping consensus clade A peptides spanning the entire proteome. Confirmatory ELISpot assays were performed.
Results: The median viral load for this cohort was 4,098 copies/ml (IQR 442.5-33,015) and the median absolute CD4 count was 498 (IQR 382-688) cells/μl. 42.8% of the women possessed protective HLA alleles (i.e. HLA-B*57/B58:01 and HLA-B*81:01). 95.2% of the women made Gag-specific CD8+ T cell responses. The median magnitude of Gag responses for this cohort was 3,767 spots and the median breadth was 20 peptides. Gag responses dominated the cumulative magnitude at (36.9%), followed by Pol (24.5%), Env (17.8%), Vif/Vpu/Tat/Rev (11.6%) and Nef (8.9%).
Conclusions: The high frequency of protective HLA class I alleles and high breadth of Gag CD8+ T cell responses in this cohort suggest an important role for host immunogenetics in mediating viral control and LTNP status. Further characterization of immune-mediated mechanisms of viral control in this cohort are warranted.
