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.
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.
Authors: Tahira P Alves; Todd Hulgan; Pingsheng Wu; Timothy R Sterling; Samuel E Stinnette; Peter F Rebeiro; Andrew J Vincz; Marino Bruce; T Alp Ikizler Journal: Clin J Am Soc Nephrol Date: 2010-09-28 Impact factor: 8.237
Authors: Paul E Sax; Camlin Tierney; Ann C Collier; Eric S Daar; Katie Mollan; Chakra Budhathoki; Catherine Godfrey; Nasreen C Jahed; Laurie Myers; David Katzenstein; Awny Farajallah; James F Rooney; Belinda Ha; William C Woodward; Judith Feinberg; Karen Tashima; Robert L Murphy; Margaret A Fischl Journal: J Infect Dis Date: 2011-10-15 Impact factor: 5.226
Authors: E K Déti; R Thiébaut; F Bonnet; S Lawson-Ayayi; M Dupon; D Neau; J L Pellegrin; D Malvy; S Tchamgoué; F Dabis; P Morlat Journal: HIV Med Date: 2009-12-09 Impact factor: 3.180
Authors: Sara Lodi; Andrew Phillips; Roger Logan; Ashley Olson; Dominique Costagliola; Sophie Abgrall; Ard van Sighem; Peter Reiss; José M Miró; Elena Ferrer; Amy Justice; Neel Gandhi; Heiner C Bucher; Hansjakob Furrer; Santiago Moreno; Susana Monge; Giota Touloumi; Nikos Pantazis; Jonathan Sterne; Jessica G Young; Laurence Meyer; Rémonie Seng; Francois Dabis; Marie-Anne Vandehende; Santiago Pérez-Hoyos; Inma Jarrín; Sophie Jose; Caroline Sabin; Miguel A Hernán Journal: Lancet HIV Date: 2015-07-07 Impact factor: 12.767
Authors: Chris T Longenecker; Douglas Kitch; Paul E Sax; Eric S Daar; Camlin Tierney; Samir K Gupta; Grace A McComsey Journal: J Acquir Immune Defic Syndr Date: 2015-06-01 Impact factor: 3.731
Authors: Jason Cheung; Rainer Puhr; Kathy Petoumenos; David A Cooper; Ian Woolley; Manoji Gunathilake; Nigel Raymond; Rick Varma; Catherine C O'Connor; David M Gracey Journal: Nephrology (Carlton) Date: 2018-08 Impact factor: 2.506
Authors: Christina M Wyatt; Douglas Kitch; Samir K Gupta; Camlin Tierney; Eric S Daar; Paul E Sax; Belinda Ha; Kathleen Melbourne; Grace A McComsey Journal: J Acquir Immune Defic Syndr Date: 2014-09-01 Impact factor: 3.731
Authors: Lloyd Mulenga; Patrick Musonda; Albert Mwango; Michael J Vinikoor; Mary-Ann Davies; Aggrey Mweemba; Alexandra Calmy; Jeffrey S Stringer; Olivia Keiser; Benjamin H Chi; Gilles Wandeler Journal: Clin Infect Dis Date: 2014-02-27 Impact factor: 9.079