Common clinical conditions age, low BMI, ritonavir use, mild renal impairment affect tenofovir pharmacokinetics in a large cohort of HIV-infected women

Baxi, Sanjiv M.a; Greenblatt, Ruth M.a,b,c; Bacchetti, Peterc; Scherzer, Rebeccaa; Minkoff, Howardd; Huang, Yonge; Anastos, Kathrynf; Cohen, Mardgeg; Gange, Stephen J.h; Young, Maryi; Shlipak, Michael G.a,j; Gandhi, Monicaa

AIDS:
doi: 10.1097/QAD.0000000000000033
Clinical Science
Abstract

Objective: Tenofovir is used commonly in HIV treatment and prevention settings, but factors that correlate with tenofovir exposure in real-world settings are unknown.

Design: Intensive pharmacokinetic studies of tenofovir in a large, diverse cohort of HIV-infected women over 24 h at steady state were performed and factors that influenced exposure [assessed by areas under the concentration–time curves (AUCs)] identified.

Methods: HIV-infected women (n = 101) on tenofovir-based therapy underwent intensive 24-h pharmacokinetic sampling. Data on race/ethnicity, age, exogenous steroid use, menstrual cycle phase, concomitant medications, recreational drugs and/or tobacco, hepatic and renal function, weight, and BMI were collected. Multivariable models using forward stepwise selection identified factors associated with effects on AUC. Glomerular filtration rates (GFRs) prior to starting tenofovir were estimated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation using both creatinine and cystatin-C measures.

Results: The median (range) of tenofovir AUCs was 3350 (1031–13 911) ng × h/ml. Higher AUCs were associated with concomitant ritonavir use (1.33-fold increase, P = 0.002), increasing age (1.21-fold increase per decade, P = 0.0007), and decreasing BMI (1.04-fold increase per 10% decrease in BMI). When GFR was calculated using cystatin-C measures, mild renal insufficiency prior to tenofovir initiation was associated with higher subsequent exposure (1.35-fold increase when pre-tenofovir GFR <70 ml/min, P = 0.0075).

Conclusion: Concomitant ritonavir use, increasing age, decreasing BMI, and lower GFR prior to tenofovir initiation as estimated by cystatin C were all associated with elevated tenofovir exposure in a diverse cohort of HIV-infected women. Clinicians treating HIV-infected women should be aware of common clinical conditions that affect tenofovir exposure when prescribing this medication.

Author Information

aDepartment of Medicine

bDepartment of Clinical Pharmacy

cDepartment of Epidemiology and Biostatistics, University of California San Francisco (UCSF), San Francisco, California

dDepartment of Medicine, SUNY Downstate Medical Center, Brooklyn, New York

eDepartment of Bioengineering and Therapeutic Sciences, University of California San Francisco (UCSF), San Francisco, California

fDepartment of Medicine, Albert Einstein University, Bronx, New York

gDepartment of Medicine, Stroger Hospital and Rush University, Chicago, Illinois

hDepartment of Medicine, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland

iDepartment of Medicine, Georgetown University Medical Center, Washington DC

jSection of General Internal Medicine, San Francisco Veterans Affairs Medical Center, San Francisco, California, USA.

Correspondence to Monica Gandhi, MD, MPH, Professor of Medicine, Division of HIV/AIDS, UCSF, 405 Irving Street, 2nd floor, San Francisco, CA 94122, USA. Tel: +1 415 502 6285; fax: +1 415 476 8528; e-mail: monica.gandhi@ucsf.edu

Received 24 June, 2013

Revised 13 August, 2013

Accepted 14 August, 2013

© 2014 Lippincott Williams & Wilkins, Inc.