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Impact of early versus deferred antiretroviral therapy on estimated glomerular filtration rate in HIV-positive individuals in the START trial

Achhra, AC; Mocroft, A; Ross, M; Ryom-Nielson, L; Avihingsanon, A; Bakowska, E; Belloso, W; ... INSIGHT START Study Group, .; + view all (2017) Impact of early versus deferred antiretroviral therapy on estimated glomerular filtration rate in HIV-positive individuals in the START trial. International Journal of Antimicrobial Agents , 50 (3) pp. 453-460. 10.1016/j.ijantimicag.2017.04.021. Green open access

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Abstract

BACKGROUND: Both untreated HIV infection and antiretroviral therapy (ART) have been associated with worsening kidney function. The impact of earlier ART initiation on kidney function has not been studied. METHODS: The START trial was a randomized comparison of immediate versus deferred ART initiation among HIV+ persons with CD4+ counts >500 cells/mm(3). Serum creatinine and urine dipstick protein were measured at baseline, months 1, 4, 8, 12, and annually thereafter. We compared the two arms for changes in estimated glomerular filtration rate (eGFR, using the CKD-EPI equation) over time using longitudinal mixed models. FINDINGS: Of 4685 START participants, 4629 (n=2294 in immediate and 2335 in deferred arm) individuals were included. Median baseline CD4 and eGFR were 651 cells/mm(3) and 111⋅5 mL/min/1⋅73m(2). ART was initiated in 2271 participants (99%) in the immediate and 1127 participants (48%) in the deferred arm, accounting for over 94% and 19% of follow-up time, respectively. Overall, 89% started ART using a tenofovir-based regimen. Over a median follow-up of 2⋅1 years, the mean eGFR was 0⋅56 (95% CI: 0⋅003-1⋅11) mL/min/1⋅73m(2) higher in the immediate arm than the deferred arm. This difference was more prominent after adjustment for current use of tenofovir or boosted-protease inhibitors (1⋅85, 95% CI: 1⋅21-2⋅50), and was more prominent in participants of black race (30% overall) (3⋅90, 95% CI: 2⋅84-4⋅97) compared to non-black (1⋅05, 95% CI: 0⋅33-1⋅77) (p<0⋅001 for interaction). Relative risk for proteinuria in the immediate vs. deferred arm was 0⋅74 (95% CI: 0⋅55-1⋅00), P=0⋅049. The incidence of chronic kidney disease as defined by eGFR < 60 or dipstick proteinuria was low, and there was no significant difference between treatment arms (incidence rate ratio 0.79, 95% CI 0.59-1.05). CONCLUSION: In the short-term, immediate ART initiation was associated with a modestly higher eGFR and lower risk of proteinuria as opposed to deferring ART- a difference more pronounced in those with black race. Whether this early benefit translates into a lower risk of chronic kidney disease requires further follow-up.

Type: Article
Title: Impact of early versus deferred antiretroviral therapy on estimated glomerular filtration rate in HIV-positive individuals in the START trial
Location: Netherlands
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.ijantimicag.2017.04.021
Publisher version: http://doi.org/10.1016/j.ijantimicag.2017.04.021
Language: English
Additional information: © 2017 Elsevier B.V. and International Society of Chemotherapy. All rights reserved. This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: CKD, HAART, HIV, START, eGFR, kidney, renal function
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute for Global Health
URI: https://discovery.ucl.ac.uk/id/eprint/1564944
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