Pharmacokinetics of Tenofovir Diphosphate, Lamivudine Triphosphate and Emtricitabine Triphosphate in Adolescents With HIV Infection With and Without Tuberculosis Coinfection

Background There is limited data on the cellular pharmacokinetics (PK) of the nucleos(t)ide reverse transcriptase inhibitors (NRTIs) in adolescents with HIV (AWH). We examined the steady-state concentrations of the NRTIs anabolites in dried blood spots (DBS) and peripheral blood mononuclear cells (PBMCs) in AWH and those with tuberculosis (TB) confection on rifampin-containing TB treatment. Methods AWH and TB/HIV coinfection on TB treatment receiving tenofovir (TFV) disoproxil fumarate (TDF) 300 mg/lamivudine (3TC) 300 mg or emtricitabine (FTC) 200 mg daily for at least 8 weeks were enrolled. DBS were collected at the study entry. Following 2 weeks of telephone adherence reminders, DBS sampling was repeated, and 4 PBMC samples were collected between 10 and 20 hours postdose. Concentrations of TFV diphosphate (TFV-DP), 3TC triphosphate and FTC triphosphate in DBS and PBMCs were measured. Adherence based on TFV-DP concentrations in DBS and the anabolites concentrations in DBS and PBMCs were compared by TB coinfection status, and ≤14 versus >14 years old. Results Of 52 participants (46.2% with TB), the median (interquartile range) age 15.0 (14.5-17.0) years, 25 (48.1%) were male. Adherence based on TFV-DP in DBS was not significantly different by TB coinfection status or age group. The concentrations of the anabolites in DBS and PBMCs were similar in AWH and TB/HIV coinfection and ≤14 versus >14 years of age; and median concentrations at the population level were similar to historical values in adults. Conclusions The concentrations of the recommended NRTIs and pharmacokinetics-determined adherence were not significantly different in adolescents with TB or younger age.