Long-term impact of immediate versus deferred antiretroviral therapy on kidney health in people with HIV

Abstract

People with human immunodeficiency virus (HIV) are at risk for chronic kidney disease (CKD) due to HIV and antiretroviral therapy (ART) nephrotoxicity. Immediate ART initiation reduces mortality and is now the standard of care, but the long-term impact of prolonged ART exposure on CKD is unknown. To evaluate this, the Strategic Timing of Antiretroviral Treatment (START) trial randomized 4,684 ART-naïve adults with CD4 cell count under 500 cells/mm³ to immediate versus deferred ART. We previously reported a small but statistically significantly greater decline in estimated glomerular filtration rate (eGFR) over a median of 2.1 years in participants randomized to deferred versus immediate ART. Here, we compare the incidence of CKD events and changes in eGFR and urine albumin/creatinine ratio (UACR) in participants randomized to immediate versus deferred ART during extended follow-up. Over a median of 9.3 years, eight participants experienced kidney failure or kidney-related death, three in the immediate and five in the deferred ART arms, respectively. Over a median of five years of more comprehensive follow-up, the annual rate of eGFR decline was 1.19 mL/min/1.73m²/year, with no significant difference between treatment arms (difference deferred - immediate arm 0.055; 95% confidence interval -0.106, 0.217 mL/min/1.73m²). Results were similar in models adjusted for baseline covariates associated with CKD, including UACR and APOL1 genotype. Similarly, there was no significant difference between treatment arms in incidence of confirmed UACR 30 mg/g or more (odds ratio 1.13; 95% confidence interval 0.85, 1.51). Thus, our findings provide the most definitive evidence to date in support of the long-term safety of early ART with respect to kidney health.

Keywords: APOL1; albuminuria; chronic kidney disease; glomerular filtration rate; nephrotoxicity.

Figure 1 |. Cumulative exposure to potentially nephrotoxic antiretroviral agents.

ART, antiretroviral therapy; DRV, darunavir; PI, protease inhibitor with or without a pharmacoenhancer; TDF, tenofovir disoproxil fumarate.

Figure 2 |. Change in estimated glomerular filtration rate (eGFR) from baseline by treatment arm.

ART, antiretroviral therapy.

Figure 3 |. Change in log10-transformed UACR from baseline by treatment arm.

CI, confidence interval; UACR, urine albumin:creatinine ratio.