The association between APOL1 risk alleles and longitudinal kidney function differs by HIV viral suppression status

Clin Infect Dis. 2015 Feb 15;60(4):646-52. doi: 10.1093/cid/ciu765. Epub 2014 Oct 3.

Abstract

Background: Existing data suggest that human immunodeficiency virus (HIV)-infected African Americans carrying 2 copies of the APOL1 risk alleles have greater risk of kidney disease than noncarriers. We sought to determine whether HIV RNA suppression mitigates APOL1-related kidney function decline among African Americans enrolled in the Multicenter AIDS Cohort Study.

Methods: We genotyped HIV-infected men for the G1 and G2 risk alleles and ancestry informative markers. Mixed-effects models were used to estimate the annual rate of estimated glomerular filtration rate (eGFR) decline, comparing men carrying 2 (high-risk) vs 0-1 risk allele (low-risk). Effect modification by HIV suppression status (defined as HIV type 1 RNA level <400 copies/mL for >90% of follow-up time) was evaluated using interaction terms and stratified analyses.

Results: Of the 333 African American men included in this study, 54 (16%) carried the APOL1 high-risk genotype. Among HIV-infected men with unsuppressed viral loads, those with the high-risk genotype had a 2.42 mL/minute/1.73 m(2) (95% confidence interval [CI], -3.52 to -1.32) faster annual eGFR decline than men with the low-risk genotype. This association was independent of age, comorbid conditions, baseline eGFR, ancestry, and HIV-related factors. In contrast, the rate of decline was similar by APOL1 genotype among men with sustained viral suppression (-0.16 mL/minute/1.73 m(2)/year; 95% CI, -.59 to .27; P for interaction <.001).

Conclusions: Unsuppressed HIV-infected African Americans with the APOL1 high-risk genotype experience an accelerated rate of kidney function decline; HIV suppression with antiretroviral therapy may reduce these deleterious renal effects.

Keywords: HIV; antiretroviral therapy; genetic; kidney disease.

Publication types

  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • African Americans / genetics*
  • Alleles
  • Antiretroviral Therapy, Highly Active
  • Apolipoprotein L1
  • Apolipoproteins / genetics*
  • Cohort Studies
  • Follow-Up Studies
  • Genetic Predisposition to Disease
  • Genotype
  • Glomerular Filtration Rate* / genetics
  • HIV / genetics
  • HIV / physiology*
  • HIV Infections / drug therapy
  • HIV Infections / physiopathology*
  • HIV Infections / virology*
  • Humans
  • Kidney / physiopathology*
  • Lipoproteins, HDL / genetics*
  • Male
  • RNA, Viral / blood
  • Risk Factors
  • Viral Load

Substances

  • APOL1 protein, human
  • Apolipoprotein L1
  • Apolipoproteins
  • Lipoproteins, HDL
  • RNA, Viral