Skip to main content
OpenTrials
Completed

NCT Number: NCT03800394

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

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.

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Human Immunodeficiency Virus (HIV) Acquired Immunodeficiency Syndrome Actinomycetales Infections Bacterial Infections Bacterial Infections and Mycoses Blood-Borne Infections Coinfection Communicable Diseases Genital Diseases Gram-Positive Bacterial Infections HIV Infections Immune System Diseases Immunologic Deficiency Syndromes Infections Lentivirus Infections Mycobacterium Infections RNA Virus Infections Retroviridae Infections Sexually Transmitted Diseases Sexually Transmitted Diseases, Viral Slow Virus Diseases Tuberculosis Urogenital Diseases Virus Diseases

Age range

10 year–19 year

Sex eligibility

All sexes

Study type

Observational

Primary location

Kwame Nkrumah University of Science and Technology

Kumasi, Ghana

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • HIV-infected adolescents aged 10 to 19 years old who are stable on antiretroviral regimen containing TDF/FTC (300/200 mg daily) for at least 8 weeks.

Exclusion criteria

  • Unable to obtain informed signed consent from parent(s) or legal guardian.
  • Pregnant or breast feeding.
  • Require therapy for other opportunistic infections other than tuberculosis (TB).

Treatment and study plan

Observational PK study

Other

Effect of antituberculosis treatment, age and genetic factors on intracellular TFV-DP and FTC-TP concentrations

Primary outcomes

  1. Average concentration (Cav) of intracellular TFV-DP and FTC-TP in Ghanaian HIV-infected adolescents.

    Time frame: After at least 8 weeks of HIV therapy.

    Mean and median Cav of intracellular TFV-DP and FTC-TP in Ghanaian HIV-infected adolescents.

  2. Area under the time-concentration curve 0-24 hours (AUC0-24h) of intracellular TFV-DP and FTC-TP in Ghanaian HIV-infected adolescents.

    Time frame: After at least 8 weeks of HIV therapy.

    Mean and median AUC0-24h of intracellular TFV-DP and FTC-TP in Ghanaian HIV-infected adolescents.

  3. Cav of TFV-DP and FTC-TP PK in HIV-infected adolescents with and without TB coinfection.

    Time frame: After at least 8 weeks of HIV therapy.

    Geometric mean intracellular TFV-DP and FTC-TP Cav in adolescents with TB/HIV coinfection compared to those only HIV infection.

  4. AUC0-24h of TFV-DP and FTC-TP PK in HIV-infected adolescents with and without TB coinfection.

    Time frame: After at least 8 weeks of HIV therapy.

    Geometric mean of intracellular TFV-DP and FTC-TP AUC0-24h in adolescents with TB/HIV coinfection compared to those with only HIV infection.

Secondary outcomes

  1. Effect of age on TFV-DP and FTC-TP Cav.

    Time frame: After at least 8 weeks of HIV therapy.

    Geometric mean of intracellular TFV-DP and FTC-TP Cav in adolescents aged 10 - 14 years old compared to that in adolescents aged 15 - 19 years old.

  2. Effect of age on TFV-DP and FTC-TP AUC0-24h .

    Time frame: After at least 8 weeks of HIV therapy.

    Geometric mean of intracellular TFV-DP and FTC-TP AUC0-24h in adolescents aged 10 - 14 years old compared to that in adolescents aged 15 - 19 years old.

  3. Intracellular TFV-DP and FTC-TP Cav in adolescents compared to that in historical adult controls.

    Time frame: After at least 8 weeks of HIV therapy.

    Geometric mean of intracellular TFV-DP and FTC-TP Cav in Ghanaian HIV-infected adolescent compared to published values in adults treated with similar dosage.

  4. Intracellular TFV-DP and FTC-TP AUC0-24h in adolescents compared to that in historical adult controls.

    Time frame: After at least 8 weeks of HIV therapy.

    Geometric mean of intracellular TFV-DP and FTC-TP AUC0-24h in Ghanaian HIV-infected adolescent compared to published values in adults treated with similar dosage.

  5. Relationship between Adenosine triphosphate (ATP)-binding cassette subfamily C, member 2 (ABCC2), member 4 (ABCC4) and member 10 (ABCC10) SNPs and TFV-DP and FTC-TP AUC0-24h.

    Time frame: After at least 8 weeks of HIV therapy.

    Relationship between ABCC2, ABCC4 and ABCC10 SNPs and intracellular TFV-DP and FTC-TP AUC0-24h.

  6. Prevalence and covariates of intracellular TFV-DP Cav < 95 fmol/106 cells in adolescents.

    Time frame: After at least 8 weeks of HIV therapy.

    Proportion of Ghanaian adolescents and factors associated with intracellular TFV-DP average concentration < 95 fmol/106 cells.

Sponsors and collaborators

Lead sponsor

University of Florida

Other

Collaborators

  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Registry information

Official study title

Pharmacokinetics of Anti-tuberculosis and Antiretroviral Drugs in Children

Important dates

Study start
2019
Primary completion
2024
Study completion
2024
First posted
Jan 11, 2019
Registry last updated
Aug 7, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.