title: Common clinical conditions - age, low BMI, ritonavir use, mild renal impairment - affect tenofovir pharmacokinetics in a large cohort of HIV-infected women.
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.
  
  
  METHODS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: 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.
authors.forename: Sanjiv M
authors.initials: SM
authors.lastname: Baxi
authors.forename: Ruth M
authors.initials: RM
authors.lastname: Greenblatt
authors.forename: Peter
authors.initials: P
authors.lastname: Bacchetti
authors.forename: Rebecca
authors.initials: R
authors.lastname: Scherzer
authors.forename: Howard
authors.initials: H
authors.lastname: Minkoff
authors.forename: Yong
authors.initials: Y
authors.lastname: Huang
authors.forename: Kathryn
authors.initials: K
authors.lastname: Anastos
authors.forename: Mardge
authors.initials: M
authors.lastname: Cohen
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Gange
authors.forename: Mary
authors.initials: M
authors.lastname: Young
authors.forename: Michael G
authors.initials: MG
authors.lastname: Shlipak
authors.forename: Monica
authors.initials: M
authors.lastname: Gandhi
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D000328:Adult; D000367:Age Factors; D019380:Anti-HIV Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D015992:Body Mass Index; D015331:Cohort Studies; D005260:Female; D005919:Glomerular Filtration Rate; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D008875:Middle Aged; D063065:Organophosphonates / Q000493:pharmacokinetics* / Q000627:therapeutic use; D011446:Prospective Studies; D051437:Renal Insufficiency; D019438:Ritonavir / Q000627:therapeutic use; D000068698:Tenofovir; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents; D063065:Organophosphonates; D000068698:Tenofovir; D000225:Adenine; D019438:Ritonavir