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

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 24h 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 (1031-13911) ngxh/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 <70ml/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.