APOL1 Genotype and HIV Infection: 20-Year Outcomes for CKD, Cardiovascular Disease, and Hypertension.

INTRODUCTION: APOL1 variant alleles substantially increase the risk for chronic kidney disease (CKD) in Black individuals, especially in the setting of HIV infection; however, their impact on hypertension and cardiovascular disease (CVD) is unclear. METHODS: Black persons with HIV (n = 1194) followed in the AIDS Clinical Trials Group (ACTG) observational studies A5001 and A5322 were genotyped for APOL1 risk alleles. Cox proportional hazard models were used to assess associations between APOL1 genotype and incident CKD, CVD, and hypertension, and linear mixed effects models were used to examine associations with longitudinal estimated glomerular filtration rate (eGFR) and proteinuria. Plasma HIV-1 viral suppression was evaluated as an effect modifier. RESULTS: APOL1 genotype was associated with CKD, but not with hypertension or CVD, although CVD events were infrequent in this relatively young cohort. Annual rates of eGFR decline and proteinuria were greater among persons with APOL1 risk alleles, including a detrimental effect of 1 APOL1 risk allele, which only became evident in the second decade of follow-up. Sustained HIV-1 viral suppression did not alter the association between incident CKD and APOL1 genotype; however, it was associated with a slower rate of eGFR decline and less proteinuria in participants with at least 1 APOL1 risk allele, including individuals with eGFRs above the CKD threshold throughout follow-up. CONCLUSION: Among treated persons with HIV, APOL1 risk alleles were associated with CKD and eGFR decline, including an effect of 1 APOL1 risk allele which took longer to manifest and was greater in individuals who did not achieve sustained viral suppression. Conversely, no association between APOL1 risk alleles and incident hypertension or CVD was detected.