@article{cd74439593f245198d405f6427df7996,
title = "Cumulative and current exposure to potentially nephrotoxic antiretrovirals and development of chronic kidney disease in HIV-positive individuals with a normal baseline estimated glomerular filtration rate: A prospective international cohort study",
abstract = "Background: Whether or not the association between some antiretrovirals used in HIV infection and chronic kidney disease is cumulative is a controversial topic, especially in patients with initially normal renal function. In this study, we aimed to investigate the association between duration of exposure to antiretrovirals and the development of chronic kidney disease in people with initially normal renal function, as measured by estimated glomerular filtration rate (eGFR). Methods: In this prospective international cohort study, HIV-positive adult participants (aged ≥16 years) from the D:A:D study (based in Europe, the USA, and Australia) with first eGFR greater than 90 mL/min per 1·73 m2 were followed from baseline (first eGFR measurement after Jan 1, 2004) until the occurrence of one of the following: chronic kidney disease; last eGFR measurement; Feb 1, 2014; or final visit plus 6 months (whichever occurred first). Chronic kidney disease was defined as confirmed (>3 months apart) eGFR lower than 60 mL/min per 1·73 m2. The primary outcome was the occurrence of chronic kidney disease. Poisson regression was used to estimate the incidence rate of chronic kidney disease associated with cumulative exposure to tenofovir disoproxil fumarate, ritonavir-boosted atazanavir, ritonavir-boosted lopinavir, other ritonavir-boosted protease inhibitors, or abacavir. Findings: Between Jan 1, 2004, and July 26, 2013, 23905 eligible individuals from the D:A:D study were included. Participants had a median baseline eGFR of 110 mL/min per 1·73 m2 (IQR 100-125), a median age of 39 years (33-45), and median CD4 cell count of 441 cells per mm3 (294-628). During a median follow-up of 7·2 years (IQR 5·1-8·9), 285 (1%) of 23905 people developed chronic kidney disease (incidence 1·76 per 1000 person-years of follow-up [95% CI 1·56-1·97]). After adjustment, we recorded a significant increase in chronic kidney disease associated with each additional year of exposure to tenofovir disoproxil fumarate (adjusted incidence rate ratio 1·14 [95% CI 1·10-1·19], p<0·0001), ritonavir-boosted atazanavir (1·20 [1·13-1·26], p<0·0001), and ritonavir-boosted lopinavir (1·11 [1·06-1·16], p<0·0001), but not other ritonavir-boosted protease inhibitors or abacavir. Interpretation: In people with normal renal function, the annual incidence of chronic kidney disease increased for up to 6 years of exposure to tenofovir disoproxil fumarate, ritonavir-boosted atazanavir, or ritonavir-boosted lopinavir therapy. Although the absolute number of new cases of chronic kidney disease was modest, treatment with these antiretrovirals might result in an increasing and cumulative risk of chronic kidney disease. Patients on potentially nephrotoxic antiretrovirals or at high risk of chronic kidney disease should be closely monitored. Funding: The Highly Active Antiretroviral Therapy Oversight Committee. {\textcopyright} 2016 Elsevier Ltd.",
keywords = "abacavir, antiretrovirus agent, atazanavir, creatinine, indinavir, lopinavir, proteinase inhibitor, ritonavir, tenofovir disoproxil, anti human immunodeficiency virus agent, tenofovir, acquired immune deficiency syndrome, adolescent, adult, Article, cardiovascular disease, CD4 lymphocyte count, chronic kidney disease, creatinine clearance, diabetes mellitus, dust exposure, female, follow up, glomerulus filtration rate, hepatitis B, human, Human immunodeficiency virus infected patient, Human immunodeficiency virus infection, hypertension, major clinical study, male, nephrotoxicity, priority journal, sensitivity analysis, urolithiasis, virus load, Australia, clinical trial, complication, drug effects, Europe, HIV Infections, middle aged, pathophysiology, prospective study, Renal Insufficiency, Chronic, United States, young adult, Adolescent, Adult, Anti-HIV Agents, Atazanavir Sulfate, Female, Glomerular Filtration Rate, Humans, Male, Middle Aged, Prospective Studies, Tenofovir, Young Adult",
author = "A. Mocroft and J.D. Lundgren and M. Ross and C.A. Fux and P. Reiss and O. Moranne and P. Morlat and A.D. Monforte and O. Kirk and L. Ryom and Ferran Torres",
note = "Cited By :123 Export Date: 17 February 2022 Correspondence Address: Mocroft, A.; Department of Infection and Population Health, Rowland Hill Street, United Kingdom; email: a.mocroft@ucl.ac.uk Chemicals/CAS: abacavir, 136470-78-5, 188062-50-2; atazanavir, 198904-31-3; creatinine, 19230-81-0, 60-27-5; indinavir, 150378-17-9, 157810-81-6, 180683-37-8; lopinavir, 192725-17-0; proteinase inhibitor, 37205-61-1; ritonavir, 155213-67-5; tenofovir disoproxil, 202138-50-9; tenofovir, 147127-19-3, 147127-20-6; Anti-HIV Agents; Atazanavir Sulfate; Tenofovir Funding details: Merck Funding details: Gilead Sciences Funding details: Janssen Biotech Funding details: Janssen Pharmaceuticals Funding details: Food and Drug Administration, FDA Funding details: Seventh Framework Programme, FP7, 260694 Funding text 1: AM has received speaker fees, travel support, or honoraria from Gilead, Pfizer, Merck, BMS, BI, and Wragge LLC. CAF has received personal fees from Gilead, AbbVie, Janssen, and ViiV, outside the submitted work. OM has received honoraria, speaker fees, travel support, or honoraria from Gilead. PR has received grants from Gilead Sciences, ViiV Healthcare, Janssen, Bristol-Myers Squibb, and Merck, and personal fees, travel support and/or honoraria from Gilead Science, Janssen, and ViiV Healthcare, outside the submitted work. PM has received personal fees and non-financial support from ViiV Healthcare, Gilead, and BMS, and personal fees from Janssen and MSD, outside the submitted work. Ad'AM has received personal fees from AbbVie, Janssen, MSD, and ViiV Healthcare, and grants and personal fees from BMS and Gilead, outside the submitted work. The other authors declare no competing interests. Funding text 2: The content of this report is solely the responsibility of the authors and does not necessarily represent the official views of the funders of the D:A:D study. The D:A:D study was supported by the Highly Active Antiretroviral Therapy Oversight Committee, the European Agency for the Evaluation of Medicinal Products, the US Food and Drug Administration, the patient community, and the following pharmaceutical companies with licensed anti-HIV drugs in the European Union: AbbVie, Bristol-Myers Squibb, Gilead Sciences Inc, ViiV Healthcare, Merck & Co Inc, and Janssen Pharmaceuticals. Full funding acknowledgments are in the appendix . References: Mocroft, A., Vella, S., Benfield, T.L., Changing patterns of mortality across Europe in patients infected with HIV-1. 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year = "2016",
month = jan,
doi = "10.1016/S2352-3018(15)00211-8",
language = "English",
volume = "3",
pages = "e23--e32",
journal = "The Lancet HIV",
issn = "2352-3018",
publisher = "Elsevier Limited",
number = "1",
}