Apoliproprotein-1 ( APOL1 ) Risk Variants and Associated Kidney Phenotypes in an Adult HIV Cohort in Nigeria

Background: HIV-positive adults are at risk for various kidney diseases, and apolipoprotein 1 (APOL1) high-risk genotypes increase this risk. This study aimed to determine the prevalence and ethnic distribution of APOL1 risk genotypes among a cohort of HIV-positive Nigerian adults and to explore the relationship between APOL1 risk variant status and albuminuria and estimated glomerular filtration rate (eGFR). Methods: We conducted a cross-sectional study among 2458 persons living with HIV who attended an HIV clinic in northern Nigeria and had received antiretroviral therapy (ART) for a minimum of six months. We collected two urine samples 4-8 weeks apart to measure albumin excretion, and blood samples to measure eGFR and determine APOL1 genotype. Findings: The frequency of the APOL1 high-risk (HR) genotype was 6·2%, which varied by ethnic group: Hausa/Fulani (2%), Igbo (49·1%), and Yoruba (14·5%). The prevalence of microalbuminuria (urine/albumin creatinine ratio [uACR] 30 – 300 mg/g) was 37%, and the prevalence of macroalbuminuria (uACR > 300 mg/g) was 3%. The odds of microalbuminuria and macroalbuminuria were higher for participants with the APOL1 HR genotype compared to those carrying the low-risk (LR) genotype (aOR = 1·97, 95% confidence interval [CI] 1·38-2·82; aOR = 4·01, 95% CI 1·98-8·12; respectively). APOL1 HR genotype participants were also at higher risk of having both eGFR 300 mg/g (aOR = 5·85, 95% CI 1·66-20·62). Interpretation: We found a high proportion of HIV-positive, ART-experienced, and largely virologically suppressed adults had microalbuminuria. Although the high-risk APOL1 genotype was less prevalent than expected, it was strongly associated with albuminuria. Future investigations are needed to determine the etiology of the high rate of microalbuminuria in this population within the context of controlled HIV infection and to determine long-term kidney outcomes. Trial Registration: The study was registered with clinicaltrials.gov (NCT03201939) and the Pan African Clinical Trials Registry (PACTR201711002808414). Funding Statement: This work is supported by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the National Institutes of Health (NIH), U01 DK112271. Declaration of Interests: The authors declare that they have no competing interests. Ethics Approval Statement: The study was approved by the Institutional Review Board of Vanderbilt University Medical Center (FW5756) and the Ethics Committee of AKTH (FWA00026225).