NCT03800394

Pharmacokinetics of Intracellular TFV-DP and FTC-TP in HIV-infected Adolescents

Pharmacokinetics of Anti-tuberculosis and Antiretroviral Drugs in Children

• Status: Completed
• Phase: —
• Study type: Observational
• Enrollment: 52 (actual)
• Sponsor: University of Florida · Academic / Other
• Sex: All
• Age: 10 Years – 19 Years
• Healthy volunteers: Not accepted

Summary

Tenofovir (TFV) disoproxil fumarate (TDF) plus emtricitabine (FTC) or lamivudine (3TC) is the preferred nucleoside backbone of first-line antiretroviral therapy (ART) for adolescents in sub-Saharan Africa. In addition, TDF/FTC is recommended for preexposure prophylaxis (PrEP) for human immunodeficiency virus (HIV) infection in adolescents at substantial risk of acquisition of HIV infection, as well as for hepatitis B virus (HBV) treatment in those with HBV/HIV coinfection. The efficacy TDF and FTC are dependent on intracellular concentrations of the active phosphate anabolites, called TFV diphosphate (TFV-DP) and FTC triphosphate (FTC-TP). However, the intracellular pharmacokinetics of TFV-DP and FTC-TP to examine the adequacy of current dosages in African adolescents has not been previously studied. Thus, examining the pharmacokinetics (PK) of these widely used antiretrovirals in African adolescents is important as ART outcomes remain poor and the recommended dosages of these drugs for children and adolescent were extrapolated from drug approval clinical trials in adult in the United States and Europe.

Detailed description

This study will evaluate the intracellular PK of TFV-DP and FTC-TP in Ghanaian HIV-infected adolescents with and without TB coinfection. As the clinical effects of TDF and FTC are related to the intracellular concentrations of the phosphate anabolites, called TFV-DP and FTC-TP, there is a need to understand the cellular pharmacology of TDF interactions in African HIV-infected adolescents with and without TB, as the study team cannot extrapolate from US patients not on antituberculosis (anti-TB) drugs. This study will enroll HIV-infected adolescents aged 10 to 18 years old with and without TB coinfection who are already established on ART. The study team hypothesize that younger age, adenosine triphosphate (ATP)-binding cassette subfamily C (ABCC) single nucleotide polymorphisms (SNPs) and anti-TB therapy may influence the intracellular TFV-DP and FTC-TP concentrations in adolescents.

Conditions

• Human Immunodeficiency Virus (HIV)
• Tuberculosis
• Coinfection

Interventions

Type	Name	Description
OTHER	Observational PK study	Effect of antituberculosis treatment, age and genetic factors on intracellular TFV-DP and FTC-TP concentrations

Timeline

• Start date: 2019-01-28
• Primary completion: 2024-05-31
• Completion: 2024-07-31
• First posted: 2019-01-11
• Last updated: 2024-08-07

Locations

1 site across 1 country: Ghana