TY - JOUR
T1 - Long-term impact of immediate versus deferred antiretroviral therapy on kidney health in people with HIV
AU - INSIGHT START Study Group
AU - Pelchen-Matthews, Annegret
AU - Mocroft, Amanda
AU - Ryom, Lene
AU - Ross, Michael J.
AU - Sharma, Shweta
AU - Coca, Steven
AU - Achhra, Amit
AU - Cornell, Elaine
AU - Tracy, Russell
AU - Phillips, Andrew
AU - Alonso, Marta Montero
AU - Toulomi, Giota
AU - Agan, Brian K.
AU - Medland, Nicholas
AU - Wyatt, Christina M.
N1 - Publisher Copyright:
© 2024 International Society of Nephrology
PY - 2024/7
Y1 - 2024/7
N2 - 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.
AB - 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.
KW - APOL1
KW - albuminuria
KW - chronic kidney disease
KW - glomerular filtration rate
KW - nephrotoxicity
UR - http://www.scopus.com/inward/record.url?scp=85193423447&partnerID=8YFLogxK
U2 - 10.1016/j.kint.2024.04.010
DO - 10.1016/j.kint.2024.04.010
M3 - Article
C2 - 38697479
AN - SCOPUS:85193423447
SN - 0085-2538
VL - 106
SP - 136
EP - 144
JO - Kidney International
JF - Kidney International
IS - 1
ER -