Sanjiv M Baxi1, Rebecca Scherzer, Ruth M Greenblatt, Howard Minkoff, Anjali Sharma, Mardge Cohen, Mary A Young, Alison G Abraham, Michael G Shlipak. 1. aDepartment of Medicine, University of California, San Francisco bSchool of Public Health, University of California, Berkeley cGeneral Internal Medicine Division, San Francisco Veterans Affairs Medical Center dDepartment of Clinical Pharmacy eDepartment of Epidemiology and Biostatistics, University of California, San Francisco, California fDivision of Infectious Diseases, State University of New York, Downstate Medical Center, Brooklyn, New York gDepartment of Medicine, Albert Einstein College of Medicine, Bronx, New York hCORE Center/Division of Infectious Diseases, John H. Stroger Jr. Hospital of Cook County, Chicago, Illinois iDepartment of Medicine, Georgetown University Medical Center, Washington DC jDepartment of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.
Abstract
OBJECTIVE: Tenofovir disoproxil fumarate is a commonly used antiretroviral drug, but risk factors for tenofovir (TFV)-associated kidney disease are not fully understood. We used intensive pharmacokinetic studies in a cohort of HIV-infected women on TFV-based therapy to study the relationship between TFV exposure and subsequent kidney function. DESIGN: This is a nested study within the Women's Interagency HIV Study, a multicenter, prospective cohort of HIV-infected women. Participants on TFV-based therapy underwent 24-h intensive pharmacokinetic sampling after witnessed dose. Kidney function was measured over the succeeding 7 years by serum creatinine [estimated glomerular filtration rate calculated by serum creatinine (eGFRcr)]. METHODS: Multivariable linear mixed models evaluated the relationship of baseline TFV area under the-time concentration curves (AUCs) with subsequent changes in kidney function. Covariates included age, diabetes, hypertension, race, BMI, ritonavir use, duration of TFV exposure, current CD4 cell count, and HIV viral load. RESULTS: Of the 105 participants, persons within the highest baseline TFV AUC tertile had significantly lower eGFRcr compared with those in the lowest tertile (mean ± standard error: 80 ± 4.3 vs. 104 ± 2.5 ml/min per 1.73 m, P < 0.0001). By year 7, this difference widened (72 ± 4.9 vs. 105 ± 2.9, P < 0.0001). After multivariable adjustment, TFV AUC in the highest tertile remained associated with lower eGFRcr relative to values in the lowest tertile at both baseline (-15 ml/min per 1.73 m, P = 0.0047) and year 7 (-23 ml/min per 1.73 m, P = 0.0002). CONCLUSION: Through intensive TFV pharmacokinetic sampling, we found a strong association between greater TFV exposure and subsequent decline in kidney function. Variations in TFV drug exposure may partially account for subsequent nephrotoxicity in persons infected with HIV.
OBJECTIVE:Tenofovir disoproxil fumarate is a commonly used antiretroviral drug, but risk factors for tenofovir (TFV)-associated kidney disease are not fully understood. We used intensive pharmacokinetic studies in a cohort of HIV-infectedwomen on TFV-based therapy to study the relationship between TFV exposure and subsequent kidney function. DESIGN: This is a nested study within the Women's Interagency HIV Study, a multicenter, prospective cohort of HIV-infectedwomen. Participants on TFV-based therapy underwent 24-h intensive pharmacokinetic sampling after witnessed dose. Kidney function was measured over the succeeding 7 years by serum creatinine [estimated glomerular filtration rate calculated by serum creatinine (eGFRcr)]. METHODS: Multivariable linear mixed models evaluated the relationship of baseline TFV area under the-time concentration curves (AUCs) with subsequent changes in kidney function. Covariates included age, diabetes, hypertension, race, BMI, ritonavir use, duration of TFV exposure, current CD4 cell count, and HIV viral load. RESULTS: Of the 105 participants, persons within the highest baseline TFV AUC tertile had significantly lower eGFRcr compared with those in the lowest tertile (mean ± standard error: 80 ± 4.3 vs. 104 ± 2.5 ml/min per 1.73 m, P < 0.0001). By year 7, this difference widened (72 ± 4.9 vs. 105 ± 2.9, P < 0.0001). After multivariable adjustment, TFV AUC in the highest tertile remained associated with lower eGFRcr relative to values in the lowest tertile at both baseline (-15 ml/min per 1.73 m, P = 0.0047) and year 7 (-23 ml/min per 1.73 m, P = 0.0002). CONCLUSION: Through intensive TFV pharmacokinetic sampling, we found a strong association between greater TFV exposure and subsequent decline in kidney function. Variations in TFV drug exposure may partially account for subsequent nephrotoxicity in persons infected with HIV.
Authors: Sonia Rodríguez-Nóvoa; Pablo Labarga; Antonio D'avolio; Pablo Barreiro; Marta Albalate; Eugenia Vispo; Carmen Solera; Marco Siccardi; Stefano Bonora; Giovanni Di Perri; Vincent Soriano Journal: AIDS Date: 2010-04-24 Impact factor: 4.177
Authors: Amandine Gagneux-Brunon; Pierre Delanaye; Nicolas Maillard; Anne Fresard; Thierry Basset; Eric Alamartine; Frédéric Lucht; Hans Pottel; Christophe Mariat Journal: AIDS Date: 2013-06-19 Impact factor: 4.177
Authors: S M Baxi; R M Greenblatt; P Bacchetti; M Cohen; J A DeHovitz; K Anastos; S J Gange; M A Young; B E Aouizerat Journal: Pharmacogenomics J Date: 2017-05-02 Impact factor: 3.550
Authors: Sanjiv M Baxi; Rebecca Scherzer; Vasantha Jotwani; Michelle M Estrella; Alison G Abraham; Chirag R Parikh; Michael R Bennett; Mardge H Cohen; Marek J Nowicki; Deborah R Gustafson; Anjali Sharma; Mary A Young; Michael G Shlipak Journal: J Acquir Immune Defic Syndr Date: 2017-04-15 Impact factor: 3.731
Authors: Julie B Dumond; Camden P Bay; Julie A E Nelson; Angel Davalos; Andrew Edmonds; Kristina De Paris; Craig Sykes; Kathryn Anastos; Roopali Sharma; Seble Kassaye; Bani Tamraz; Audrey L French; Stephen Gange; Ighovwerha Ofotokun; Margaret A Fischl; David E Vance; Adaora A Adimora Journal: Antimicrob Agents Chemother Date: 2020-08-20 Impact factor: 5.191
Authors: Jim Aizire; Kristina M Brooks; Mark Mirochnick; Patricia M Flynn; Kevin Butler; Jennifer J Kiser; George K Siberry; Terry Fenton; Mae Cababasay; Mary G Fowler Journal: J Acquir Immune Defic Syndr Date: 2020-02-01 Impact factor: 3.771
Authors: Ahizechukwu C Eke; Kristina M Brooks; Rahel D Gebreyohannes; Jeanne S Sheffield; Kelly E Dooley; Mark Mirochnick Journal: Expert Opin Drug Metab Toxicol Date: 2020-03-17 Impact factor: 4.936
Authors: Giuseppe Lapadula; Davide Paolo Bernasconi; Salvatore Casari; Franco Maggiolo; Roberto Cauda; Massimo Di Pietro; Nicoletta Ladisa; Laura Sighinolfi; Sarah Dal Zoppo; Francesca Sabbatini; Alessandro Soria; Chiara Pezzoli; Annalisa Mondi; Silvia Costarelli; Maria Grazia Valsecchi; Carlo Torti; Andrea Gori Journal: PLoS One Date: 2016-09-15 Impact factor: 3.240
Authors: Jasmine R Marcelin; Melody L Berg; Eugene M Tan; Hatem Amer; Nathan W Cummins; Stacey A Rizza Journal: PLoS One Date: 2016-02-12 Impact factor: 3.240