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

NCT03800394 | Completed

• 2 other identifiers: IRB201801820 - PKAdol2R01HD071779
• Study Type: observational
• Target: 52
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Human Immunodeficiency Virus (HIV); Tuberculosis; Coinfection

Keywords

Pharmacokinetic; Pharmacogenomic; Tenofovir diphosphate; Emtricitabine triphosphate; Adolescents

Outcome Measures

Primary Outcomes (4)

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

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

  After at least 8 weeks of HIV therapy.

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

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

  After at least 8 weeks of HIV therapy.

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

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

  After at least 8 weeks of HIV therapy.

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

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

  After at least 8 weeks of HIV therapy.

Secondary Outcomes (6)

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

  After at least 8 weeks of HIV therapy.

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

  After at least 8 weeks of HIV therapy.

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

  After at least 8 weeks of HIV therapy.

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

  After at least 8 weeks of HIV therapy.

• 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.

  After at least 8 weeks of HIV therapy.

Study Arms (2)

HIV only

Adolescents aged 10-19 years with HIV infection

Other: Observational PK study

HIV/TB

Adolescents aged 10-19 years with HIV and TB coinfection

Other: Observational PK study

Interventions

Observational PK study OTHER

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

HIV only; HIV/TB

Eligibility Criteria

• Age: 10 Years - 19 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Adolescents aged 10-19 years with HIV with or without TB co-infection.

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• University of Florida: lead
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator

Study Sites (1)

Kwame Nkrumah University of Science and Technology

Kumasi, Ghana

Location

Biospecimen

Retention: SAMPLES WITH DNA

Peripheral mononuclear cells (PBMCs) and deoxyribonucleic acid (DNA)

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome; Tuberculosis; Coinfection

Condition Hierarchy (Ancestors)

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses

Study Officials

• Awewura Kwara, MD

  University of Florida

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 3, 2019
• First Posted: January 11, 2019
• Study Start: January 28, 2019
• Primary Completion: May 31, 2024
• Study Completion: July 31, 2024
• Last Updated: August 7, 2024

Record last verified: 2024-08

Locations

GH (1)