ObjectivesHuman immunodeficiency virus type 2 (HIV-2) progression to disease is significantly slower than that of human immunodeficiency virus type 1 (HIV-1). Genetic determinants for susceptibility to disease progression were hypothesized to play a more significant role in this infection compared with HIV-1. We sought to identify common human lymphocyte antigen (HLA) alleles in the Senegalese population and to compare HLA profiles between HIV-2–infected individuals with low and high risk for disease progression.Study Design/MethodsWe conducted a case–control study investigating possible associations between MHC class I genes and the risk of disease progression in HIV-2–infected individuals. The MHC class I genotype was molecularly defined using polymerase chain reaction with sequence specific primers (PCR-SSP) in 62 female sex workers from the Dakar, Senegal cohort. Lack of antibodies to the HIV-2 antigen p26 has been previously shown to predict disease progression and was used in this study as a surrogate marker. Twenty-one cases were identified lacking antibodies to p26, therefore at a higher risk of disease progression, and were compared with 41 p26 antibody-positive, randomly selected controls.ResultsStatistical analysis showed that HLA B35 was significantly associated with lack of p26 antibodies, and higher risk of disease progression (p< 0.05). The same association was found for the self-defined class I haplotypes B35-Cw4 and A23-Cw7 (p< 0.05). The HLA B53 allele was associated with slower disease progression; however, this association was not statistically significant. We observed a trend whereby heterozygotes were at lower risk for HIV-2 disease progression, as previously reported in HIV-1 disease.ConclusionsIn this West African population, a distinct profile of HLA class I alleles was observed, and many of these appear to influence disease progression in HIV-2 infection.