Abstract
Apolipoprotein L1 (APOL1) has broad innate immune functions and has been shown to restrict HIV replication in vitro by multiple mechanisms. Coding variants in APOL1 are strongly associated with HIV-associated nephropathy (HIVAN) in persons with untreated HIV infection; however, the mechanism by which APOL1 variant protein potentiates renal injury in the presence of high viral load is not resolved. Little is known about the association of APOL1 genotypes with HIV viral load, HIV acquisition, or progression to AIDS. We assessed the role of APOL1 coding variants on HIV-1 acquisition using the conditional logistic regression test, on viral load using the t-test or ANOVA, and on progression to AIDS using Cox proportional hazards models among African Americans enrolled in the ALIVE HIV natural history cohort (n = 775). APOL1 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. APOL1 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 APOL1 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.
Highlights
Apolipoprotein L1 (APOL1) is a human innate immune factor against African trypanosomes responsible for human African trypanosomiasis [1]
We evaluate the genetic associations between APOL1 variants and HIV type 1 (HIV-1) acquisition, set-point viral load, and rate of progression to AIDS among African Americans enrolled in the ALIVE HIV-1 cohort
Adjusting for sex and age did not affect the results (Table 1). These results suggest that APOL1 risk variants have no impact on host susceptibility to HIV-1 acquisition
Summary
Apolipoprotein L1 (APOL1) is a human innate immune factor against African trypanosomes responsible for human African trypanosomiasis (or sleeping sickness) [1]. Two common APOL1 variants, G1 (rs73885319, p.S342G) and G2 (a 6-bp in-frame deletion removing two amino acids, rs71785313, p.N388_Y389del), extend APOL1 restriction to T.b.rhodesiense, the cause of acute human African trypanosomiasis These variants are found only in individuals with recent African ancestry. The lifetime risk of HIVAN, a form of collapsing focal segmental glomerulosclerosis associated with rapid progression to end-stage renal disease, is ∼10% in African Americans with untreated HIV infection [6, 7]. APOL1 was shown to target HIV-1 Gag for degradation by the endolysosomal pathway and to deplete HIV-1 Vif, which counteracts the APOBEC3G host restriction factor in lysosomes [12] It remains unknown if variant APOL1 affects HIV acquisition, viral replication, or HIV disease progression. We evaluate the genetic associations between APOL1 variants and HIV-1 acquisition, set-point viral load, and rate of progression to AIDS among African Americans enrolled in the ALIVE HIV-1 cohort
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