Impact of Genetic Variants on HIV-1 Infection and Disease Progression.

Apolipoprotein L1 (APOL1) has broad innate immune functions and has been shown to restrict HIV replication by multiple mechanisms. Coding variants in are strongly associated with HIV-associated nephropathy (HIVAN) in persons with untreated HIV infection; however, the mechanism by which variant protein potentiates renal injury in the presence of high viral load is not resolved. Little is known about the association of genotypes with HIV viral load, HIV acquisition, or progression to AIDS. We assessed the role of coding variants on HIV-1 acquisition using the conditional logistic regression test, on viral load using the test or ANOVA, and on progression to AIDS using Cox proportional hazards models among African Americans enrolled in the ALIVE HIV natural history cohort ( = 775). variants were not associated with susceptibility to HIV-1 acquisition by comparing genotype frequencies between HIV-1 positive and exposed or at-risk HIV-1 uninfected groups (recessive model, 12.8 vs. 12.5%, respectively; OR 1.02, 95% CI 0.62-1.70). Similar null results were observed for dominant and additive models. variants were not associated with HIV-1 viral load or with risk of progression to AIDS [Relative hazards (RH) 1.33, 95% CI 0.30-5.89 and 0.96, 95% CI 0.49-1.88, for recessive and additive models, respectively]. In summary, we found no evidence that variants are associated with host susceptibility to HIV-1 acquisition, set-point HIV-1 viral load or time to incident AIDS. These results suggest that APOL1 variants are unlikely to influence HIV infection or progression among individuals of African ancestry.