HLA Class i Alleles Associated with Mortality in Thai Military Recruits with HIV-1 CRF01-AE Infection

In HIV-1-infected patients, variation at the HLA class I locus is associated with disease progression, but few studies have assessed the influence of HLA alleles on HIV-1 CRF01-AE infection, which is dominant in Thailand. We hypothesized that alleles predicted to confer more effective immune responses, such as HLA-B∗46, would protect against disease progression. HLA typing was performed on HIV-1 incident cases surviving until 1998-1999 and HIV-1-negative matched controls from Thai army cohorts enrolled between 1991 and 1995. We assessed associations between class I alleles and disease progression subsequent to HLA typing. Ninety-nine HIV-1-incident cases were followed for a median of 3.7 years after HLA typing; during this time, 58 participants died. Two alleles were associated with mortality: HLA B∗51 was protective (3-year survival B∗51^pos vs. B∗51^neg: 75% vs. 52%; p = 0.034) whereas Cw∗04 was deleterious (3-year survival Cw∗04^pos vs. Cw∗04^neg: 39% vs. 60%; p = 0.027). HLA-B∗46 was not associated with disease progression. Alleles present at different frequencies in HIV-1-incident compared with HIV-1-negative men included HLA-A∗02:03, B∗35, B∗15, and C∗08. 1. In conclusion in this Thai army cohort, HLA-B∗51 was associated with lower mortality, confirming that this allele, which is protective in clade B HIV-1 infection, has a similar effect on HIV CRF01-AE infection. The deleterious effect of HLA-Cw∗04 must be interpreted with caution because it may be in linkage disequilibrium with disease-susceptible HLA-B alleles. We did not find that HLA-B∗46 was protective. These findings may inform vaccine development for areas of the world in which HIV-1 CRF01-AE infection is prevalent.