Abstract
AIMS: Demographics and kidney function contribute to variability in lamivudine and tenofovir drug concentrations. The aim was to assess, for the first time, the pharmacokinetic variability of lamivudine and tenofovir in Papua New Guinean (PNG) HIV/AIDS patients. METHODS: For 121 PNG HIV/AIDS patients receiving combination antiretroviral therapy (300 mg lamivudine, 300 mg tenofovir disoproxil fumarate, 600 mg efavirenz, single tablet once daily), age, body weight, sex and serum creatinine concentrations data were recorded. Plasma lamivudine and tenofovir concentrations were simultaneously quantified by liquid chromatography-tandem mass spectrometry. Univariate and multivariate linear regression analyses were performed to assess the association of demographic covariates and kidney function with plasma lamivudine and tenofovir concentrations. RESULTS: Excluding 9 patients with plasma lamivudine and tenofovir concentrations below the lower limits of quantitation, median (range) plasma lamivudine and tenofovir concentrations were 188 (15.5-1099) and 64.4 (15-251) ng/mL, respectively, and were highly correlated (Spearman ρ = 0.75, P < 2.2 × 10(-16)). Twenty-seven percent of patients had plasma tenofovir concentrations below the therapeutic range. Less than 5% of the interindividual variability in concentrations was explained by age, body weight and sex. In 29 patients with serum creatinine data collected within 4 days of plasma for lamivudine and tenofovir concentrations, there were no significant associations between estimated glomerular filtration rate or creatinine clearance and tenofovir (P > .8) or lamivudine (P > .4) concentrations. CONCLUSION: A specific, precise and accurate method was validated for the simultaneous quantitation of tenofovir and lamivudine in human plasma and was successfully applied to PNG HIV/AIDS patients to reveal large and correlated interpatient variability in tenofovir and lamivudine exposure.