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.