AUTHOR=An Ping , Kirk Gregory D. , Limou Sophie , Binns-Roemer Elizabeth , Kopp Jeffrey B. , Winkler Cheryl A. 

TITLE=Impact of APOL1 Genetic Variants on HIV-1 Infection and Disease Progression

JOURNAL=Frontiers in Immunology

VOLUME=10

YEAR=2019

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2019.00053

DOI=10.3389/fimmu.2019.00053

ISSN=1664-3224

ABSTRACT=<p>Apolipoprotein L1 (APOL1) has broad innate immune functions and has been shown to restrict HIV replication <italic>in vitro</italic> by multiple mechanisms. Coding variants in <italic>APOL1</italic> are strongly associated with HIV-associated nephropathy (HIVAN) in persons with untreated HIV infection; however, the mechanism by which <italic>APOL1</italic> variant protein potentiates renal injury in the presence of high viral load is not resolved. Little is known about the association of <italic>APOL1</italic> genotypes with HIV viral load, HIV acquisition, or progression to AIDS. We assessed the role of <italic>APOL1</italic> coding variants on HIV-1 acquisition using the conditional logistic regression test, on viral load using the <italic>t-</italic>test or ANOVA, and on progression to AIDS using Cox proportional hazards models among African Americans enrolled in the ALIVE HIV natural history cohort (<italic>n</italic> = 775). <italic>APOL1</italic> 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. <italic>APOL1</italic> 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 <italic>APOL1</italic> 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.</p>