Pediatric HIV InfectionPhase 1NCT05069688
Dolutegravir Pharmacokinetics Among HIV/TB Coinfected Children Receiving Standard and High-dose Rifampicin
A Phase 1 study testing rifampicin in people with Pediatric HIV Infection and Tuberculosis Infection, run by Brigham and Women's Hospital at 1 site in Nigeria.
Trial summary
Tuberculosis (TB) is the leading cause of death among children with HIV, yet insufficient data are available on the pharmacokinetics of newer HIV/TB cotreatment strategies in children. Read more about this study
- Who is it for?
- Ages 4 weeks to 5 years
- Conditions the study is for
- Pediatric HIV Infection, Tuberculosis Infection
- What is being tested?
- rifampicin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteNigeria
- Study dates
- 7 Jul 2023to 31 Dec 2026
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
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 4 weeks to 5 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- ART-naïve or ART-experienced HIV-infected children between 4 weeks and <6 years of age
- Active TB diagnosis
- Weight of at least 3 kilograms
- Consent of the parent or legal guardian
Who cannot join
- Baseline labs with evidence of ≥grade 3 abnormalities: ALT, total bilirubin, absolute neutrophil count (ANC), platelets, or creatinine
- Suspected TB meningitis or presenting with acute respiratory distress or decompensation
- Receipt of a medication that has drug-drug interactions with dolutegravir or rifampicin
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Nigeria1 site, 1 recruiting
- Recruiting
University College Hospital/ University of Ibadan
Ibadan, Oyo State
Regina Oladokun, MD
About this study
Official title: Mind the Gaps: Pharmacokinetic Research to Advance Pediatric HIV/TB Cotreatment and TB Prevention
Tuberculosis (TB) is the leading cause of death among children with HIV, yet insufficient data are available on the pharmacokinetics of newer HIV/TB cotreatment strategies in children. Current WHO-recommended rifampicin dosages result in low concentrations in most children, and high-dose rifampicin may improve outcomes and shorten treatment duration. Yet the impact of high-dose rifampicin on dolutegravir exposures has not been examined in children. This study aims to evaluate the safety and pharmacokinetics of dolutegravir twice daily among HIV/TB coinfected children receiving standard-dose and high-dose rifampicin.
Read the detailed description
This study is a prospective, single-arm, open-label, intensive and sparse pharmacokinetic (PK) and safety study to evaluate steady-state dolutegravir (DTG) concentrations among 20 HIV/TB coinfected children 4 weeks to <6 years of age requiring concurrent TB treatment. Ten patients will be recruited into each of two age cohorts: 4 weeks to <2 years and ≥2 years to <6 years.
Children will be recruited from two large pediatric HIV clinics in Nigeria. Children in this study will receive HIV/TB cotreatment that is considered standard of care consisting of DTG twice daily during rifampicin (RIF)-containing TB treatment. For this portion of the study, the primary intervention is additional blood sampling for drug concentration determination and biomarker assessment. Additionally, during a two week period (study weeks 20-21), the RIF dose will be increased from standard-dose to high-dose RIF, during which two-way PK and toxicity monitoring will occur. Clinical and laboratory monitoring for toxicity during HIV/TB cotreatment is consistent with routine care.
PK sampling for drug concentration determination will occur at three time points during the 48-week study. Specifically, PK sampling will occur at week-20 to evaluate DTG twice daily during standard-dose RIF, week-22 to evaluate DTG twice daily during high-dose RIF, and at week-30 to evaluate DTG once daily after TB treatment is complete.
Additionally, the endogenous biomarker of CYP3A4 activity, 4-beta-hydroxycholesterol to cholesterol ratio, will be evaluated to advance understanding of underlying mechanisms of drug action. Blood sampling to quantify this biomarker will occur at either 4 (among ART-experienced children) or 5 (ART-naive) time points during the 48-week study.
- Conditions
- Pediatric HIV Infection, Tuberculosis Infection
- Being tested
- rifampicin
- Keywords
- pharmacokinetic, dolutegravir, rifampicin
- Medical subject headings
- Latent Tuberculosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
rifampicinDrug
Patients will receive standard TB and HIV treatment, however, for two weeks (study weeks 20-21) the dose of rifampicin will be increased from standard-dose to high-dose to assess pharmacokinetics and safety
| Study group | Role | What they receive |
|---|---|---|
| Dolutegravir PK during standard and high-dose rifampicin | Experimental | This is a single arm study: all patients are started on HIV/TB cotreatment considered standard of care and then for two weeks (study weeks 20-21) high-dose rifampicin is given during which safety and pharmacokinetics are examined. Receives: Drug: rifampicin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dolutegravir AUC during standard-dose rifampicin
Dolutegravir area under the concentration time curve (AUC) will be compared to therapeutic ranges established in the adult and pediatric literature
Measured: week 20
Dolutegravir AUC during high-dose rifampicin
Dolutegravir AUC will be compared against therapeutic ranges established in the literature and during standard-dose rifampicin
Measured: week 22
Secondary outcomes (3)
Rifampicin maximum concentration (Cmax) during standard-dose rifampicin
Rifampicin Cmax will be determined during standard rifampicin
Measured: week 20
Rifampicin Cmax during high-dose rifampicin
Rifampicin Cmax will be determined during high-dose rifampicin and compared to that observed during standard-dose rifampicin
Measured: week 22
Proportion of participants experiencing severe (grade 3 or 4) clinical or laboratory adverse events
Laboratory and clinical toxicities are monitored at 8 time points throughout the study and the proportion of children experiencing severe adverse events will be determined
Measured: Week 48
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Oct 2021
- Study start7 Jul 2023
- Primary completion31 Dec 2026 (estimated)
- Study completion31 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pediatric HIV InfectionStudies of the same condition, open and under way.
- More trials run by Brigham and Women's HospitalThe 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
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Prospective single-arm, open-label, pharmacokinetic and safety study
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Brigham and Women's Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- APIN Public Health Initiatives, University of Cape Town
- Responsible party
- Principal investigator, Holly Rawizza, M.D., M.P.H., Brigham and Women's Hospital
- Investigators
- Holly Rawizza, MD, MPH, Principal investigator, Brigham and Women's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05069688
- Sponsor's protocol ID
- 2021P002401
- Status last verified
- Jul 2026
- First submitted
- 16 Sep 2021
- Last updated
- 30 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: At the request of researchers de-identified data may be shared.
Study at a glance
From the registry record, last updated by the sponsor on 30 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Mind the Gaps: Pharmacokinetic Research to Advance Pediatric HIV/TB Cotreatment and TB Prevention
- ClinicalTrials.gov ID
- NCT05069688
- Acronym / sponsor ID
- 2021P002401
- Conditions
- Pediatric HIV Infection, Tuberculosis Infection
- Keywords
- pharmacokinetic, dolutegravir, rifampicin
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- Brigham and Women's HospitalUniversity, hospital or other
- Collaborators
- APIN Public Health Initiatives, University of Cape Town
- Study start
- 7 Jul 2023 (actual)
- Primary completion
- 31 Dec 2026 (estimated)
- Study completion
- 31 Dec 2026 (estimated)
- First posted
- 6 Oct 2021 (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.
Tuberculosis (TB) is the leading cause of death among children with HIV, yet insufficient data are available on the pharmacokinetics of newer HIV/TB cotreatment strategies in children. Current WHO-recommended rifampicin dosages result in low concentrations in most children, and high-dose rifampicin may improve outcomes and shorten treatment duration. Yet the impact of high-dose rifampicin on dolutegravir exposures has not been examined in children. This study aims to evaluate the safety and pharmacokinetics of dolutegravir twice daily among HIV/TB coinfected children receiving standard-dose and high-dose rifampicin.
Detailed description
This study is a prospective, single-arm, open-label, intensive and sparse pharmacokinetic (PK) and safety study to evaluate steady-state dolutegravir (DTG) concentrations among 20 HIV/TB coinfected children 4 weeks to <6 years of age requiring concurrent TB treatment. Ten patients will be recruited into each of two age cohorts: 4 weeks to <2 years and ≥2 years to <6 years.
Children will be recruited from two large pediatric HIV clinics in Nigeria. Children in this study will receive HIV/TB cotreatment that is considered standard of care consisting of DTG twice daily during rifampicin (RIF)-containing TB treatment. For this portion of the study, the primary intervention is additional blood sampling for drug concentration determination and biomarker assessment. Additionally, during a two week period (study weeks 20-21), the RIF dose will be increased from standard-dose to high-dose RIF, during which two-way PK and toxicity monitoring will occur. Clinical and laboratory monitoring for toxicity during HIV/TB cotreatment is consistent with routine care.
PK sampling for drug concentration determination will occur at three time points during the 48-week study. Specifically, PK sampling will occur at week-20 to evaluate DTG twice daily during standard-dose RIF, week-22 to evaluate DTG twice daily during high-dose RIF, and at week-30 to evaluate DTG once daily after TB treatment is complete.
Additionally, the endogenous biomarker of CYP3A4 activity, 4-beta-hydroxycholesterol to cholesterol ratio, will be evaluated to advance understanding of underlying mechanisms of drug action. Blood sampling to quantify this biomarker will occur at either 4 (among ART-experienced children) or 5 (ART-naive) time points during the 48-week study.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Prospective single-arm, open-label, pharmacokinetic and safety study
| Arm | Type | Receives |
|---|---|---|
| Dolutegravir PK during standard and high-dose rifampicin | Experimental | Drug: rifampicinThis is a single arm study: all patients are started on HIV/TB cotreatment considered standard of care and then for two weeks (study weeks 20-21) high-dose rifampicin is given during which safety and pharmacokinetics are examined. |
Who may qualify
- Ages
- 4 weeks to 5 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (4 listed)
- ART-naïve or ART-experienced HIV-infected children between 4 weeks and <6 years of age
- Active TB diagnosis
- Weight of at least 3 kilograms
- Consent of the parent or legal guardian
Key exclusion criteria (3 listed)
- Baseline labs with evidence of ≥grade 3 abnormalities: ALT, total bilirubin, absolute neutrophil count (ANC), platelets, or creatinine
- Suspected TB meningitis or presenting with acute respiratory distress or decompensation
- Receipt of a medication that has drug-drug interactions with dolutegravir or rifampicin
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 |
|---|---|---|
| rifampicinPatients will receive standard TB and HIV treatment, however, for two weeks (study weeks 20-21) the dose of rifampicin will be increased from standard-dose to high-dose to assess pharmacokinetics and safety | Drug | Dolutegravir PK during standard and high-dose rifampicin |
Primary outcome
Dolutegravir AUC during standard-dose rifampicin
Time frame: week 20
Dolutegravir area under the concentration time curve (AUC) will be compared to therapeutic ranges established in the adult and pediatric literature
Dolutegravir AUC during high-dose rifampicin
Time frame: week 22
Dolutegravir AUC will be compared against therapeutic ranges established in the literature and during standard-dose rifampicin
3 secondary outcomes
Rifampicin maximum concentration (Cmax) during standard-dose rifampicin
Time frame: week 20
Rifampicin Cmax during high-dose rifampicin
Time frame: week 22
Proportion of participants experiencing severe (grade 3 or 4) clinical or laboratory adverse events
Time frame: Week 48
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jul 2026.
- Individual participant dataSharing planned: Undecided. At the request of researchers de-identified data may be shared.
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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.
Holly Rawizza, MD, MPH principal investigator
Brigham and Women's Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing rifampicin in people with Pediatric HIV Infection and Tuberculosis Infection, run by Brigham and Women's Hospital at 1 site in Nigeria.
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 4 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: looking for participants now, as of the sponsor's last update on 30 Jul 2026. 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 Nigeria. 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.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Holly Rawizza, MD, MPH (617-432-4686, hrawizza@bwh.harvard.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Dolutegravir AUC during standard-dose rifampicin (time frame: week 20). The study lists 2 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 30 Jul 2026.