TuberculosisNCT03800407
Contributing Factors for Poor HIV Treatment Response in Children With TB/HIV Coinfection
An observational study of Tuberculosis and Human Immunodeficiency Virus, run by University of Florida at 1 site in Ghana.
Trial summary
Efavirenz (EFV)-based antiretroviral therapy (ART) remains the preferred regimen in human immunodeficiency virus (HIV)-infected children aged 3 years or older on rifampin-containing antituberculosis (anti-TB) therapy. Read more about this study
- Who is it for?
- Ages 3 to 14 years
- Conditions the study is for
- Tuberculosis, Human Immunodeficiency Virus, Coinfection
- What is being tested?
- Observational study
- How many people
- 213 participants
- Where
- 1 siteGhana
- Study dates
- 28 Jan 2019to 31 Jul 2025
- 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 3 to 14 years
- All sexes
- No healthy volunteers
- Child
Study population: Children aged 3 to 14 years old with HIV infection with or without active TB
Who may be able to join
- HIV seropositive children with or without active TB
- Antiretroviral-naïve to efavirenz and meet criteria for initiation or switch to efavirenz-based ART
- Are available for follow-up until achievement of a study endpoint like completion of study at 6 months or discontinuation of ART.
Who cannot join
- Unable to obtain informed signed consent parent(s) or legal guardian
- Have AIDS-related opportunistic infections other than TB
- History of acute hepatitis within 30 days of study entry
- Persistent vomiting or diarrhea at time of enrolment
- Hemoglobin < 6 g/dl, white blood cells < 2500/mm3, serum creatinine > 1.5 mg/dl, aspartate transaminase (AST) and alanine transaminase (ALT) > 2 times upper limit of normal
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Pharmacokinetics of Anti-tuberculosis and Antiretroviral Drugs in Children
Efavirenz (EFV)-based antiretroviral therapy (ART) remains the preferred regimen in human immunodeficiency virus (HIV)-infected children aged 3 years or older on rifampin-containing antituberculosis (anti-TB) therapy. This is because drug interactions between first-line anti-TB therapy with protease inhibitors (PIs) are more severe to adjust for, and interactions with integrase strand transfer inhibitors (INSTIs) are not well studied in that age group. Although, current weight-based EFV dosing recommendation is not optimal in some children, pharmacokinetic-treatment response (PK-PD) data to guide optimal dosing of EFV during concurrent rifampin-containing therapy in children is very limited. The study team propose that EFV concentrations outside the optimal therapeutic range in children will be associated with virologic failure due to lack of efficacy because of low concentrations or increased central nervous system (CNS) toxicities from high concentrations leading to poor medication adherence. The study will determine virological suppression rates in HIV-infected children with and without TB coinfection treated with standard efavirenz-based therapy and examine the factors contributing to poor virologic response.
Read the detailed description
In a previous study, the study team found that first-line anti-TB therapy had minimal effect on EFV pharmacokinetics (PK) at the population level, but children with TB/HIV coinfection on anti-TB therapy had a trend towards worse virologic outcome compared to those with only HIV infection. Due to the small sample size, the study team were unable to examined the patient factors contributing to the poor virologic response. The study team hypothesized that virologic suppression rates on EFV-based therapy is significantly lower in children with TB/HIV coinfection compared to those with HIV alone. In addition, virologic response will be dependent EFV plasma concentrations, CYP2B6 516 G>T genotype and/or adherence level. This hypothesis is based on the premise that extremes (low and high EFV concentration, respectively) could lead to virologic failure because of lack of efficacy or intolerable side effects leading to poor adherence. The current study will investigate the effect of anti-TB therapy, CYP2B6 genotype and pharmacokinetically determined adherence level on virologic response in children with TB/HIV coinfection treated with EFV-based ART.
- Conditions
- Tuberculosis, Human Immunodeficiency Virus, Coinfection
- Being tested
- Observational study
- Keywords
- Pharmacokinetic, Concurrent antituberculosis therapy, Efavirenz, Virologic response, Children
- Medical subject headings
- Tuberculosis, Acquired Immunodeficiency Syndrome, Coinfection
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Observational studyOther
Outcome of EFV-based ART in children with TB/HIV coinfection compared to those with HIV only on EFV-based ART
| Study group | Role | What they receive |
|---|---|---|
| EFV-based ART | ART-naïve HIV-infected children aged 3 - 14 years who initiate EFV-based ART Receives: Other: Observational study | |
| Concurrent EFV-based ART plus anti-TB therapy | ART-naïve HIV-infected children aged 3 - 14 years with TB coinfection who initiate EFV-based ART while receiving first-line anti-TB therapy Receives: Other: Observational study |
What is being measured
The primary outcome is the main question the study is designed to answer.
TB coinfection status and HIV RNA < 200 copies/mL on EFV-based ART in HIV-infected children.
The proportion of children with TB/HIV coinfection with virological suppression (HIV RNA < 200 copies/mL) on EFV-based ART and anti-TB therapy compared to that in children with only HIV infection on EFV-based therapy.
Measured: At week 24 of HIV therapy.
Secondary outcomes (5)
Efavirenz plasma mid-dose concentration and HIV RNA suppression < 200 copies/mL.
Relationship between EFV mid-dose concentration and HIV RNA suppression rate in the combined population of HIV-infected children with and without TB coinfection.
Measured: Up to week 24 of HIV therapy.
Random efavirenz concentration below the limit of detection (poor ART adherence) and HIV RNA suppression rate.
Relationship poor ART adherence and EFV-based ART response in the combined population of HIV-infected children with and without TB coinfection.
Measured: Up to week 24 of HIV therapy.
CYP2B6 516G>T genotype status and random efavirenz concentration below the limit of detection (poor ART adherence).
Relationship between CYP2B6 516G>T genotype status and likelihood of poor EFV-based ART adherence.
Measured: Up to week 24 of HIV therapy.
CYP2B6 516G>T genotype status and HIV RNA suppression < 200 copies/mL.
Relationship between CYP2B6 516G>T genotype status and likelihood of HIV RNA suppression.
Measured: Up to week 24 of HIV therapy.
TB coinfection status and risk of virological failure on EFV-based ART.
Proportion of children with TB/HIV coinfection compared to those with only HIV infection with virological failure (HIV RNA > 1000 copies/mL) at 12 months of EFV-based ART.
Measured: Up to week 48 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 Jul 2025
- Study completion31 Jul 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for TuberculosisStudies 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
- Prospective
- Enrolment
- 213 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
- NCT03800407
- Sponsor's protocol ID
- IRB201801820 TB/HIV - N
- Other IDs
- 2R01HD071779, 5R01HD071779-10
- Status last verified
- Aug 2025
- First submitted
- 3 Jan 2019
- Last updated
- 8 Aug 2025
- 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 8 Aug 2025. 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
- NCT03800407
- Acronym / sponsor ID
- IRB201801820 TB/HIV - N
- Conditions
- Tuberculosis, Human Immunodeficiency Virus, Coinfection
- Keywords
- Pharmacokinetic, Concurrent antituberculosis therapy, Efavirenz, Virologic response, Children
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 213 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 Jul 2025 (actual)
- Study completion
- 31 Jul 2025 (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.
Efavirenz (EFV)-based antiretroviral therapy (ART) remains the preferred regimen in human immunodeficiency virus (HIV)-infected children aged 3 years or older on rifampin-containing antituberculosis (anti-TB) therapy. This is because drug interactions between first-line anti-TB therapy with protease inhibitors (PIs) are more severe to adjust for, and interactions with integrase strand transfer inhibitors (INSTIs) are not well studied in that age group. Although, current weight-based EFV dosing recommendation is not optimal in some children, pharmacokinetic-treatment response (PK-PD) data to guide optimal dosing of EFV during concurrent rifampin-containing therapy in children is very limited. The study team propose that EFV concentrations outside the optimal therapeutic range in children will be associated with virologic failure due to lack of efficacy because of low concentrations or increased central nervous system (CNS) toxicities from high concentrations leading to poor medication adherence. The study will determine virological suppression rates in HIV-infected children with and without TB coinfection treated with standard efavirenz-based therapy and examine the factors contributing to poor virologic response.
Detailed description
In a previous study, the study team found that first-line anti-TB therapy had minimal effect on EFV pharmacokinetics (PK) at the population level, but children with TB/HIV coinfection on anti-TB therapy had a trend towards worse virologic outcome compared to those with only HIV infection. Due to the small sample size, the study team were unable to examined the patient factors contributing to the poor virologic response. The study team hypothesized that virologic suppression rates on EFV-based therapy is significantly lower in children with TB/HIV coinfection compared to those with HIV alone. In addition, virologic response will be dependent EFV plasma concentrations, CYP2B6 516 G>T genotype and/or adherence level. This hypothesis is based on the premise that extremes (low and high EFV concentration, respectively) could lead to virologic failure because of lack of efficacy or intolerable side effects leading to poor adherence. The current study will investigate the effect of anti-TB therapy, CYP2B6 genotype and pharmacokinetically determined adherence level on virologic response in children with TB/HIV coinfection treated with EFV-based ART.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| EFV-based ART | – | Other: Observational studyART-naïve HIV-infected children aged 3 - 14 years who initiate EFV-based ART |
| Concurrent EFV-based ART plus anti-TB therapy | – | Other: Observational studyART-naïve HIV-infected children aged 3 - 14 years with TB coinfection who initiate EFV-based ART while receiving first-line anti-TB therapy |
Who may qualify
- Ages
- 3 to 14 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
- Study population
- Children aged 3 to 14 years old with HIV infection with or without active TB
Key inclusion criteria (3 listed)
- HIV seropositive children with or without active TB
- Antiretroviral-naïve to efavirenz and meet criteria for initiation or switch to efavirenz-based ART
- Are available for follow-up until achievement of a study endpoint like completion of study at 6 months or discontinuation of ART.
Key exclusion criteria (5 listed)
- Unable to obtain informed signed consent parent(s) or legal guardian
- Have AIDS-related opportunistic infections other than TB
- History of acute hepatitis within 30 days of study entry
- Persistent vomiting or diarrhea at time of enrolment
- Hemoglobin < 6 g/dl, white blood cells < 2500/mm3, serum creatinine > 1.5 mg/dl, aspartate transaminase (AST) and alanine transaminase (ALT) > 2 times upper limit of normal
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 studyOutcome of EFV-based ART in children with TB/HIV coinfection compared to those with HIV only on EFV-based ART | Other | Concurrent EFV-based ART plus anti-TB therapy, EFV-based ART |
Primary outcome
TB coinfection status and HIV RNA < 200 copies/mL on EFV-based ART in HIV-infected children.
Time frame: At week 24 of HIV therapy.
The proportion of children with TB/HIV coinfection with virological suppression (HIV RNA < 200 copies/mL) on EFV-based ART and anti-TB therapy compared to that in children with only HIV infection on EFV-based therapy.
5 secondary outcomes
Efavirenz plasma mid-dose concentration and HIV RNA suppression < 200 copies/mL.
Time frame: Up to week 24 of HIV therapy.
Random efavirenz concentration below the limit of detection (poor ART adherence) and HIV RNA suppression rate.
Time frame: Up to week 24 of HIV therapy.
CYP2B6 516G>T genotype status and random efavirenz concentration below the limit of detection (poor ART adherence).
Time frame: Up to week 24 of HIV therapy.
CYP2B6 516G>T genotype status and HIV RNA suppression < 200 copies/mL.
Time frame: Up to week 24 of HIV therapy.
TB coinfection status and risk of virological failure on EFV-based ART.
Time frame: Up to week 48 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 8 Aug 2025.
- 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 Tuberculosis and Human Immunodeficiency Virus, 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 3 inclusion and 5 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 8 Aug 2025. 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?
TB coinfection status and HIV RNA < 200 copies/mL on EFV-based ART in HIV-infected children. (time frame: At week 24 of HIV therapy.). 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 8 Aug 2025.