Association between antiretroviral exposure and renal impairment among HIV-positive persons with normal baseline renal function: The D:A:D Study a

Lene Ryom, Amanda Mocroft, Ole Kirk, Signe W. Worm, David A. Kamara, Peter Reiss, Michael Ross, Christoph A. Fux, Philippe Morlat, Olivier Moranne, Colette Smith, Jens D. Lundgren

Research output: Contribution to journalArticle

214 Scopus citations

Abstract

Background. Several antiretroviral agents (ARVs) are associated with chronic renal impairment, but the extent of such adverse events among human immunodeficiency virus (HIV)-positive persons with initially normal renal function is unknown.Methods. D:A:D study participants with an estimated glomerular filtration rate (eGFR) of ≥90 mL/min after 1 January 2004 were followed until they had a confirmed eGFR of ≤70 mL/min (the threshold below which we hypothesized that renal interventions may begin to occur) or ≤60 mL/min (a value indicative of moderately severe chronic kidney disease [CKD]) or until the last eGFR measurement during follow-up. An eGFR was considered confirmed if it was detected at 2 consecutive measurements ≥3 months apart. Predictors and eGFR-related ARV discontinuations were identified using Poisson regression.Results. Of 22 603 persons, 468 (2.1%) experienced a confirmed eGFR of ≤70 mL/min (incidence rate, 4.78 cases/1000 person-years of follow-up [95% confidence interval "CI", 4.35-5.22]) and 131 (0.6%) experienced CKD (incidence rate, 1.33 cases/1000 person-years of follow-up [95% CI, 1.10-1.56]) during a median follow-up duration of 4.5 years (interquartile range [IQR], 2.7-6.1 years). A current eGFR of 60-70 mL/min caused significantly higher rates of discontinuation of tenofovir (adjusted incidence rate ratio [aIRR], 1.72 [95% CI, 1.38-2.14]) but not other ARVs compared with a current eGFR of ≥90 mL/min. Cumulative tenofovir use (aIRR, 1.18/year [95% CI, 1.12-1.25]) and ritonavir-boosted atazanavir use (aIRR, 1.19/year [95% CI, 1.09-1.32]) were independent predictors of a confirmed eGFR of ≤70 but were not significant predictors of CKD whereas ritonavir-boosted lopinavir use was a significant predictor for both end points (aIRR, 1.11/year [95% CI, 1.05-1.17] and 1.22/year [95% CI, 1.16-1.28], respectively). Associations were unaffected by censoring for concomitant ARV use but diminished after discontinuation of these ARVs.Conclusions. Tenofovir, ritonavir-boosted atazanavir, and ritonavir-boosted lopinavir use were independent predictors of chronic renal impairment in HIV-positive persons without preexisting renal impairment. Increased tenofovir discontinuation rates with decreasing eGFR may have prevented further deteriorations. After discontinuation, the ARV-associated incidence rates decreased.

Original languageEnglish (US)
Pages (from-to)1359-1369
Number of pages11
JournalJournal of Infectious Diseases
Volume207
Issue number9
DOIs
StatePublished - May 1 2013

Keywords

  • ART
  • HIV
  • atazanavir
  • chronic kidney disease
  • eGFR
  • lopinavir
  • nephrotoxicity
  • tenofovir

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

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    Ryom, L., Mocroft, A., Kirk, O., Worm, S. W., Kamara, D. A., Reiss, P., Ross, M., Fux, C. A., Morlat, P., Moranne, O., Smith, C., & Lundgren, J. D. (2013). Association between antiretroviral exposure and renal impairment among HIV-positive persons with normal baseline renal function: The D:A:D Study a. Journal of Infectious Diseases, 207(9), 1359-1369. https://doi.org/10.1093/infdis/jit043