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

Amit C. Achhra, Amanda Mocroft, Michael J. Ross, Lene Ryom-Nielson, Anchalee Avihingsanon, Elzbieta Bakowska, Waldo Belloso, Amanda Clarke, Hansjakob Furrer, Gregory M. Lucas, Matti Ristola, Mohammed Rassool, Jonathan Ross, Charurut Somboonwit, Shweta Sharma, Christina Wyatt

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)453-460
Number of pages8
JournalInternational Journal of Antimicrobial Agents
Volume50
Issue number3
DOIs
StatePublished - Sep 1 2017
Externally publishedYes

Fingerprint

Tenofovir
Glomerular Filtration Rate
HIV
Proteinuria
CD4 Lymphocyte Count
Creatinine
Therapeutics
Urine
Kidney
Serum
Proteins

Keywords

  • CKD
  • eGFR
  • HAART
  • HIV
  • Kidney
  • START

ASJC Scopus subject areas

  • Microbiology (medical)
  • Pharmacology (medical)
  • Infectious Diseases

Cite this

Impact of early versus deferred antiretroviral therapy on estimated glomerular filtration rate in HIV-positive individuals in the START trial. / Achhra, Amit C.; Mocroft, Amanda; Ross, Michael J.; Ryom-Nielson, Lene; Avihingsanon, Anchalee; Bakowska, Elzbieta; Belloso, Waldo; Clarke, Amanda; Furrer, Hansjakob; Lucas, Gregory M.; Ristola, Matti; Rassool, Mohammed; Ross, Jonathan; Somboonwit, Charurut; Sharma, Shweta; Wyatt, Christina.

In: International Journal of Antimicrobial Agents, Vol. 50, No. 3, 01.09.2017, p. 453-460.

Research output: Contribution to journalArticle

Achhra, AC, Mocroft, A, Ross, MJ, Ryom-Nielson, L, Avihingsanon, A, Bakowska, E, Belloso, W, Clarke, A, Furrer, H, Lucas, GM, Ristola, M, Rassool, M, Ross, J, Somboonwit, C, Sharma, S & Wyatt, C 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, vol. 50, no. 3, pp. 453-460. https://doi.org/10.1016/j.ijantimicag.2017.04.021
Achhra, Amit C. ; Mocroft, Amanda ; Ross, Michael J. ; Ryom-Nielson, Lene ; Avihingsanon, Anchalee ; Bakowska, Elzbieta ; Belloso, Waldo ; Clarke, Amanda ; Furrer, Hansjakob ; Lucas, Gregory M. ; Ristola, Matti ; Rassool, Mohammed ; Ross, Jonathan ; Somboonwit, Charurut ; Sharma, Shweta ; Wyatt, Christina. / Impact of early versus deferred antiretroviral therapy on estimated glomerular filtration rate in HIV-positive individuals in the START trial. In: International Journal of Antimicrobial Agents. 2017 ; Vol. 50, No. 3. pp. 453-460.
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