Human Immunodeficiency Virus (HIV)NCT03800394
Pharmacokinetics of Intracellular TFV-DP and FTC-TP in HIV-infected Adolescents
An observational study of Human Immunodeficiency Virus (HIV) and Tuberculosis, run by University of Florida at 1 site in Ghana.
Trial 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. Read more about this study
- Who is it for?
- Ages 10 to 19 years
- Conditions the study is for
- Human Immunodeficiency Virus (HIV), Tuberculosis, Coinfection
- What is being tested?
- Observational PK study
- How many people
- 52 participants
- Where
- 1 siteGhana
- Study dates
- 28 Jan 2019to 31 Jul 2024
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 10 to 19 years
- All sexes
- No healthy volunteers
- Child, Adult
Study population: Adolescents aged 10-19 years with HIV with or without TB co-infection.
Who may be able to join
- 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.
Who cannot join
- 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).
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Pharmacokinetics of Anti-tuberculosis and Antiretroviral Drugs in Children
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.
Read the 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.
- Being tested
- Observational PK study
- Keywords
- Pharmacokinetic, Pharmacogenomic, Tenofovir diphosphate, Emtricitabine triphosphate, Adolescents
- Medical subject headings
- Acquired Immunodeficiency Syndrome, Tuberculosis, Coinfection
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Observational PK studyOther
Effect of antituberculosis treatment, age and genetic factors on intracellular TFV-DP and FTC-TP concentrations
| Study group | Role | What they receive |
|---|---|---|
| HIV only | Adolescents aged 10-19 years with HIV infection Receives: Other: Observational PK study | |
| HIV/TB | Adolescents aged 10-19 years with HIV and TB coinfection Receives: Other: Observational PK study |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: After at least 8 weeks of HIV therapy.
Secondary outcomes (6)
Effect of age on TFV-DP and FTC-TP Cav.
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.
Measured: After at least 8 weeks of HIV therapy.
Effect of age on TFV-DP and FTC-TP AUC0-24h .
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.
Measured: After at least 8 weeks of HIV therapy.
Intracellular TFV-DP and FTC-TP Cav in adolescents compared to that in historical adult controls.
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.
Measured: 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.
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.
Measured: 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.
Relationship between ABCC2, ABCC4 and ABCC10 SNPs and intracellular TFV-DP and FTC-TP AUC0-24h.
Measured: After at least 8 weeks of HIV therapy.
Prevalence and covariates of intracellular TFV-DP Cav < 95 fmol/106 cells in adolescents.
Proportion of Ghanaian adolescents and factors associated with intracellular TFV-DP average concentration < 95 fmol/106 cells.
Measured: After at least 8 weeks of HIV therapy.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jan 2019
- Study start28 Jan 2019
- Primary completion31 May 2024
- Study completion31 Jul 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Human Immunodeficiency Virus (HIV)Studies of the same condition, open and under way.
- More trials run by University of FloridaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Cross-sectional
- Enrolment
- 52 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Florida
- Sponsor type
- University, hospital or other
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Responsible party
- Sponsor
- Investigators
- Awewura Kwara, MD, Principal investigator, University of Florida
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03800394
- Sponsor's protocol ID
- IRB201801820 - PKAdol
- Other IDs
- 2R01HD071779
- Status last verified
- Aug 2024
- First submitted
- 3 Jan 2019
- Last updated
- 7 Aug 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 7 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pharmacokinetics of Anti-tuberculosis and Antiretroviral Drugs in Children
- ClinicalTrials.gov ID
- NCT03800394
- Acronym / sponsor ID
- IRB201801820 - PKAdol
- Keywords
- Pharmacokinetic, Pharmacogenomic, Tenofovir diphosphate, Emtricitabine triphosphate, Adolescents
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 52 participants (actual)
- Lead sponsor
- University of FloridaUniversity, hospital or other
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Study start
- 28 Jan 2019 (actual)
- Primary completion
- 31 May 2024 (actual)
- Study completion
- 31 Jul 2024 (actual)
- First posted
- 11 Jan 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Cross-sectional
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| HIV only | – | Other: Observational PK studyAdolescents aged 10-19 years with HIV infection |
| HIV/TB | – | Other: Observational PK studyAdolescents aged 10-19 years with HIV and TB coinfection |
Who may qualify
- Ages
- 10 to 19 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
- Study population
- Adolescents aged 10-19 years with HIV with or without TB co-infection.
Key inclusion criteria (1 listed)
- 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.
Key exclusion criteria (3 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Observational PK studyEffect of antituberculosis treatment, age and genetic factors on intracellular TFV-DP and FTC-TP concentrations | Other | HIV only, HIV/TB |
Primary outcome
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.
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.
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.
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.
6 secondary outcomes
Effect of age on TFV-DP and FTC-TP Cav.
Time frame: After at least 8 weeks of HIV therapy.
Effect of age on TFV-DP and FTC-TP AUC0-24h .
Time frame: After at least 8 weeks of HIV therapy.
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.
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.
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.
Prevalence and covariates of intracellular TFV-DP Cav < 95 fmol/106 cells in adolescents.
Time frame: After at least 8 weeks of HIV therapy.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Aug 2024.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Awewura Kwara, MD principal investigator
University of Florida
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Human Immunodeficiency Virus (HIV) and Tuberculosis, run by University of Florida at 1 site in Ghana.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Ghana. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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.). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Aug 2024.