TY - JOUR
T1 - Association between antiretroviral exposure and renal impairment among HIV-positive persons with normal baseline renal function
T2 - The D:A:D Study a
AU - Ryom, Lene
AU - Mocroft, Amanda
AU - Kirk, Ole
AU - Worm, Signe W.
AU - Kamara, David A.
AU - Reiss, Peter
AU - Ross, Michael
AU - Fux, Christoph A.
AU - Morlat, Philippe
AU - Moranne, Olivier
AU - Smith, Colette
AU - Lundgren, Jens D.
N1 - Funding Information:
Financial support. This work was supported by the Highly Active Antiretroviral Therapy Oversight Committee (HAART-OC), a collaborative committee with representation from academic institutions, the European Agency for the Evaluation of Medicinal Products, the US Food and Drug Administration, the patient community, and all pharmaceutical companies with licensed anti-HIV drugs in the European Union (Abbott Laboratories, Boehringer Ingelheim Pharmaceuticals, Bristol-Myers Squibb, Gilead Sciences, Viiv Healthcare, Merck, Pfizer, F. Hoffman- LaRoche, and Janssen Pharmaceuticals); the Health Insurance Fund Council, Amstelveen, the Netherlands (grant CURE/97-46486 to the ATHENA cohort); and the Agence Nationale de Recherches sur le SIDA (grant Action Coordonnée no. 7, Cohortes, to the Aquitaine Cohort). AHOD is funded as part of the Asia Pacific HIV Observational Database, a program of the Foundation for AIDS Research, amfAR, and is supported in part by the National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH; grant U01-AI069907) and by unconditional grants from Merck Sharp and Dohme, Gilead Sciences, Bristol-Myers Squibb, Boehringer Ingelheim Pharmaceuticals, Roche, Pfizer, GlaxoSmithKline, and Janssen Pharmaceuticals. The Kirby Institute is funded by the Australian Government Department of Health and Ageing and is affiliated with the Faculty of Medicine, the University of New South Wales. The BASS is funded by the Fondo de Investigación Sanitaria (grant FIS 99/0887) and the Fundación para la Investigación y la Prevención del SIDA en Espanã (grant FIPSE 3171/00). The Terry Beirn Community Programs for Clinical Research on AIDS (CPCRA) is funded by the NIAID, NIH (grants 5U01AI042170-10 and 5U01AI046362-03). The EuroSIDA study is funded by the BIOMED 1 (grant CT94-1637) and BIOMED 2 (grant CT97-2713) programs, by the Fifth Framework Program of the European Commission (grant QLK2-2000-00773), and by grants from Bristol-Myers Squibb, GlaxoSmithKline, Boehringer Ingel-heim Pharmaceuticals, and Roche. The ICONA Foundation is funded by unrestricted educational grants from Abbott Laboratories, Bristol-Myers Squibb, Gilead Sciences, GSK, Pfizer, and Janssen Pharmaceutical. The SHCS is funded by the Swiss National Science Foundation.
PY - 2013/5/1
Y1 - 2013/5/1
N2 - 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.
AB - 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.
KW - ART
KW - HIV
KW - atazanavir
KW - chronic kidney disease
KW - eGFR
KW - lopinavir
KW - nephrotoxicity
KW - tenofovir
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U2 - 10.1093/infdis/jit043
DO - 10.1093/infdis/jit043
M3 - Article
C2 - 23382571
AN - SCOPUS:84875971855
SN - 0022-1899
VL - 207
SP - 1359
EP - 1369
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 9
ER -