TY - JOUR
T1 - Impact of early versus deferred antiretroviral therapy on estimated glomerular filtration rate in HIV-positive individuals in the START trial
AU - Achhra, Amit C.
AU - Mocroft, Amanda
AU - Ross, Michael
AU - Ryom-Nielson, Lene
AU - Avihingsanon, Anchalee
AU - Bakowska, Elzbieta
AU - Belloso, Waldo
AU - Clarke, Amanda
AU - Furrer, Hansjakob
AU - Lucas, Gregory M.
AU - Ristola, Matti
AU - Rassool, Mohammed
AU - Ross, Jonathan
AU - Somboonwit, Charurut
AU - Sharma, Shweta
AU - Wyatt, Christina
N1 - Publisher Copyright:
© 2017 Elsevier B.V. and International Society of Chemotherapy
PY - 2017/9
Y1 - 2017/9
N2 - The impact of early ART initiation (versus deferring) on kidney function has not been studied. START was a randomised comparison of immediate versus deferred ART initiation among HIV-positive persons with CD4+ (cells/mm3) counts >500. Serum creatinine and urine dipstick protein were measured at Months 0, 1, 4, 8 and 12, and annually thereafter. The two arms were compared for changes in eGFR (mL/min/1.73 m2, calculated by CKD-EPI equation), over time using longitudinal mixed models. Of 4685 START participants, 4629 (2294 in immediate and 2335 deferred arm) were included. Median baseline CD4+ and eGFR were 651 and 111.5, respectively. ART was initiated in 2271 participants (99.0%) in the immediate and 1127 (48.3%) in the deferred arm, accounting for >94% and >19% of follow-up time, respectively. Overall, 89% started ART using a tenofovir-based regimen. Over 2.1 years median follow-up, mean eGFR was 0.56 (95% CI 0.003–1.11) higher in the immediate versus deferred arm, which was more prominent after adjustment for current tenofovir or bPI use (1.85, 95% CI 1.21–2.50) and in Black participants (30.1% overall) (3.90, 95% CI 2.84–4.97) versus non-Blacks (1.05, 95% CI 0.33–1.77) (P < 0.001 for interaction). Relative risk for proteinuria in the immediate versus deferred arm was 0.74 (95% CI 0.55–1.00) (P = 0.049). In the short-term, immediate ART initiation was associated with a modestly higher eGFR and lower proteinuria risk versus deferring ART (more pronounced in Black participants). Whether this early benefit translates into a lower risk of CKD requires further follow-up.
AB - The impact of early ART initiation (versus deferring) on kidney function has not been studied. START was a randomised comparison of immediate versus deferred ART initiation among HIV-positive persons with CD4+ (cells/mm3) counts >500. Serum creatinine and urine dipstick protein were measured at Months 0, 1, 4, 8 and 12, and annually thereafter. The two arms were compared for changes in eGFR (mL/min/1.73 m2, calculated by CKD-EPI equation), over time using longitudinal mixed models. Of 4685 START participants, 4629 (2294 in immediate and 2335 deferred arm) were included. Median baseline CD4+ and eGFR were 651 and 111.5, respectively. ART was initiated in 2271 participants (99.0%) in the immediate and 1127 (48.3%) in the deferred arm, accounting for >94% and >19% of follow-up time, respectively. Overall, 89% started ART using a tenofovir-based regimen. Over 2.1 years median follow-up, mean eGFR was 0.56 (95% CI 0.003–1.11) higher in the immediate versus deferred arm, which was more prominent after adjustment for current tenofovir or bPI use (1.85, 95% CI 1.21–2.50) and in Black participants (30.1% overall) (3.90, 95% CI 2.84–4.97) versus non-Blacks (1.05, 95% CI 0.33–1.77) (P < 0.001 for interaction). Relative risk for proteinuria in the immediate versus deferred arm was 0.74 (95% CI 0.55–1.00) (P = 0.049). In the short-term, immediate ART initiation was associated with a modestly higher eGFR and lower proteinuria risk versus deferring ART (more pronounced in Black participants). Whether this early benefit translates into a lower risk of CKD requires further follow-up.
KW - CKD
KW - HAART
KW - HIV
KW - Kidney
KW - START
KW - eGFR
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U2 - 10.1016/j.ijantimicag.2017.04.021
DO - 10.1016/j.ijantimicag.2017.04.021
M3 - Article
C2 - 28668686
AN - SCOPUS:85027254683
SN - 0924-8579
VL - 50
SP - 453
EP - 460
JO - International Journal of Antimicrobial Agents
JF - International Journal of Antimicrobial Agents
IS - 3
ER -