Possession of HLA Class II DRB1*1303 Associates with Reduced Viral Loads in Chronic HIV-1 Clade C and B Infection

Background.The HLA class II molecules play a central role in the generation of human immunodeficiency virus (HIV)–specific CD4+ T-helper cells, which are critical for the induction of cytotoxic CD8+ T cell responses. However, little is known about the impact of HLA class II alleles on HIV disease progression. Methods.In this study we investigated the effect of HLA class II alleles on HIV disease outcome and HIV-specific T cell responses in a cohort of 426 antiretroviral therapy–naive, HIV-1 clade C–infected, predominantly female black South Africans. Results.The HLA class II allele DRB1*1303 was independently associated with lower plasma viral loads in this population (P = .02), an association that was confirmed in a second cohort of 1436 untreated, HIV-1 clade B–infected, male European Americans, suggesting that DRB1*1303-mediated protection is independent of ethnicity, sex, and viral clade. Interestingly, DRB1*1303 carriage was not associated with an increased frequency of interferon (IFN) γ–positive HIV-specific CD4+ T cell responses. Conclusions.These data demonstrate the independent effect of an HLA class II allele, DRB1*1303, on HIV disease progression, in the absence of increased IFN-γ–positive HIV-specific CD4+ T cell frequencies, suggesting that the protective activity of DRB1*1303 may be mediated via an alternative mechanism.