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 - Funding Information:
Funding: This work was supported by the National Institutes of Health (NIH), National Institute of Allergy and Infectious Diseases [UM1 AI 068641, UM1-AI120197]; the Department of Bioethics at the NIH Clinical Center; the National Cancer Institute; the National Heart, Lung, and Blood Institute; the National Institute of Mental Health; the National Institute of Neurological Disorders and Stroke; and the National Institute of Arthritis and Musculoskeletal Disorders. Financial support for START was also provided by the French Agence Nationale de Recherches sur le SIDA et les Hépatites Virales (ANRS); the Federal Ministry of Education and Research; the European AIDS Treatment Network (NEAT); the National Health and Medical Research Council; and the Medical Research Council and National Institute for Health Research. Six pharmaceutical companies (AbbVie, Inc., Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline/ViiV Healthcare, Janssen Scientific Affairs, LLC, and Merck Sharp and Dohme Corp.) donate antiretroviral drugs to START. The authors were also supported by the National Institute of Diabetes and Digestive and Kidney Diseases [R01 DK100272, P01 DK056492 and R01 DK112258 to CW] and the National Institute on Drug Abuse [K24 DA035684, R01 DA026770 to GML].
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 -