TuberculosisPhase 1/2DOLPHIN KIDSNCT05122767
Rifapentine and Isoniazid TB Preventive Therapy (3HP) for Children Taking Dolutegravir-based Antiretroviral Treatment (DOLPHIN KIDS)
A Phase 1/2 study testing Dolutegravir and 3HP in people with Tuberculosis and HIV, run by The Aurum Institute NPC at 2 sites in South Africa.
Trial summary
Single-arm, multi-center, Phase I/II clinical trial, in two groups. Individuals with HIV infection taking Efavirenz (EFV), nevirapine (NVP) or lopinavir/ritonavir (LPV/r) and two nucleoside reverse transcriptase inhibitors (NRTI) who have undetectable HIV viral load (VL) (< 50 copies/mL) and an indication for… Read more about this study
- Who is it for?
- Ages 3 months to 17 years
- Conditions the study is for
- Tuberculosis, HIV
- What is being tested?
- Dolutegravir and 3HP
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 92 participants
- Where
- 2 sitesSouth Africa
- Study dates
- 24 May 2023to 31 Dec 2025
- Phase
- Phase 1/2
- 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 3 months to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Age 3 months through 17 years
- Weight > 3 kg
- Documented HIV infection by DNA polymerase chain reaction (PCR) or plasma RNA-PCR if <18 months and by HIV-ELISA if 18 months and confirmed with a DNA PCR or RNA-PCR from an independent sample
- Undetectable HIV-1 viral load
Who cannot join
- Confirmed or suspected TB disease (evidenced by symptoms and/or clinical exam findings and/or chest radiographic findings suggestive of TB, positive mycobacterial culture or molecular TB testing, or currently on TB treatment for active TB disease)
- Likely to move from the study area during the study period
- Known exposure to TB cases with known or suspected resistance to isoniazid or rifampicin in the source case
- TB treatment within the past year
- Prior completion of a TPT course without re-exposure to persons with infectious TB since TPT completion
- Receipt of once-daily INH for >30 days that was given for at least 14 consecutive days in the 30 days prior to enrolment.
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- Sensitivity or intolerance to dolutegravir, isoniazid, or rifamycins
- Suspected acute hepatitis or known chronic or unstable liver disease^; HBsAg positivity or anti-hepatitis A virus (HAV) Immunoglobulin M (IgM) antibody; any infant born to a Hepatitis C positive mother in whom in utero infection in the infant is unknown or under evaluation
- alanine aminotransferase (ALT) > 3 times the upper limit of normal (ULN)
- Total bilirubin > 2 .5 times the ULN
- Absolute neutrophil count (ANC) ≤ 750 cells/mm3
- Estimated creatinine clearance < 60 ml/min (Bedside Schwartz formula)*
- Pregnancy or breastfeeding (infant of a breastfeeding mother is allowed)
- Women of childbearing potential who are unable or unwilling to use two forms of contraception**
- Weight for age Z score below 2 or severe clinical malnutrition
- On prohibited medications e.g. dofetilide (see Appendix 1)
- Known porphyria
Trial locations and contacts
2 sites in 1 country.
South Africa2 sites
Peri Natal HIV Research Unit - Klerksdorp Tshepong Hospital
Klerksdorp, North West, 2571
The Aurum Institute: Pretoria Clinical Research Centre
Pretoria, Gauteng, 0087
About this study
Official title: Safety, Tolerability and Drug-drug Interactions of Short-course Treatment of Latent Tuberculosis Infection With High-dose Once-weekly Rifapentine and Isoniazid (3HP) Among Infants, Children and Adolescents Living With HIV Taking Dolutegravir-based Antiretroviral Treatment
Single-arm, multi-center, Phase I/II clinical trial, in two groups. Individuals with HIV infection taking Efavirenz (EFV), nevirapine (NVP) or lopinavir/ritonavir (LPV/r) and two nucleoside reverse transcriptase inhibitors (NRTI) who have undetectable HIV viral load (VL) (< 50 copies/mL) and an indication for tuberculosis (TB) preventive treatment (TPT), will be switched to dolutegravir (DTG) with tenofovir/emtricitabine (TDF/FTC), tenofovir/lamivudine (TDF/3TC), abacavir/lamivudine (ABC/3TC) or zidovudine/lamivudine (AZT/3TC) in accordance with South African National HIV Guidelines. Groups 1 and 2 will receive weekly HP for 12 total doses starting 4 weeks after initiating DTG. Individuals who are on an existing DTG-based plus two NRTI antiretroviral therapy (ART) regimen for at least four weeks (and have not received efavirenz, or nevirapine or lopinavir/ritonavir for at least four weeks) who have an undetectable HIV viral load may also participate.
Read the detailed description
Group 1a (n=15): 15 participants aged 2-17 years of age will have suppressed viral load and take weight-based dosing of dolutegravir once daily with two nucleoside reverse transcriptase inhibitors (NRTIs) from Days 1-28. Semi-intensive pharmacokinetic (PK) sampling for dolutegravir will be performed on Day 28. Participants start twice-daily dolutegravir and will receive once-weekly rifapentine (RPT) and isoniazid (INH) (3HP) for 12 total doses beginning on Day 29. Semi-intensive PK sampling for dolutegravir will be performed on Day 46 (3 days after the 3rd dose of HP). Additional sparse PK sampling for dolutegravir (trough concentrations (CT)) will be performed on Days 44 and 48. Semi-intensive PK sampling for RPT will be performed on day 78. PK assessments will not be performed for isoniazid given that it's a well-studied drug in children. VL will be measured at baseline (week 0) and week 7 (after 3 doses of 3HP) and week 24 (8 weeks after the last dose of 3HP). Safety labs (complete blood count (CBC), urea and electrolytes (U\&E), creatinine, and liver function tests (LFT)) will be obtained at baseline (week 0), and weeks 4, 7, 12, 16, 20, and 24.
Interim analysis will occur when all Group 1a participants have completed the 7-week semi-intensive PK visit (HP week 3). Enrolment into Group 2a (but not group 1b) will commence once this interim analysis is complete. Enrolment into group 1b will not be paused during this interim analysis. The interim analysis will assess PK, safety, and VL data. PK data will be modeled to assess the appropriateness of studying once-daily DTG dosing with co-administration of 3HP. The subsequent 30-45 participants age 2-17 years of age in Group 2a will receive twice or once-daily dosing of DTG, respectively, depending on PK modeling results.
Group 1b (n=8 ): All participants less than 2 years of age with a suppressed viral load will take weight-based dosing of dolutegravir once daily with two nucleoside reverse transcriptase inhibitors (NRTIs) from Days 1-28. Semi-intensive PK sampling for dolutegravir will be performed on Day 28. Participants start twice-daily dolutegravir and will receive once-weekly HP for 12 total doses beginning on Day 29. Semi-intensive PK sampling for dolutegravir will be performed on Day 46 (3 days after the 3rd dose of HP). Additional sparse PK sampling for dolutegravir (trough concentrations (CT)) will be performed on Days 44 and 48. Semi-intensive PK sampling for RPT will be performed on day 78. PK assessments will not be performed for isoniazid given that it's a well-studied drug in children. VL will be measured at baseline (week 0) and weeks 7 and 24. Safety labs (complete blood count (CBC), urea and electrolytes (U\&E), creatinine, and liver function tests (LFT)) will be obtained at baseline (week 0), and weeks 4, 7, 12, 16, 20 and 24.
Interim analysis will occur when all Group 1b participants have completed the 7-week semi-intensive PK visit (HP week 3). Enrolment into group 2b (but not group 2a) will commence once this interim analysis is complete. Enrolment into group 2a will not be paused during this interim analysis. Interim analysis will assess PK, safety, and VL data. PK data will be modeled to assess the appropriateness of studying once-daily DTG dosing with co-administration of 3HP. The subsequent 16-24 participants in group 2b will receive twice or once-daily dosing of DTG, respectively, depending on population PK modeling results in this interim group.
Group 1b may or may not occur in parallel with Group 1a. This depends on the availability of dosing and a child-friendly formulation for 3HP in children 2 years and younger.
Group 2a (n=45 or 30): In the case where we proceed with evaluating once-daily DTG with 3HP in children 2-17 years of age, an additional 45 participants with suppressed viral load will be enrolled. In the case where we proceed with evaluating twice-daily DTG dosing with 3HP, an additional 30 participants with suppressed viral load will be enrolled. Both groups will take dolutegravir once daily from days 1-28 (weeks 1-4). On day 28, semi-intensive PK sampling for dolutegravir will be performed (prior to any HP dose). On day 29 (week 5), participants will either continue to take once daily DTG or their daily weight-based DTG dose will be increased to twice daily (based on group 1a data) and the first of the 12 HP weekly weight-based HP doses will be provided. Semi-intensive PK sampling for DTG will be performed on day 46 (2-4 days post third HP dose). Additional sparse PK sampling for dolutegravir (trough concentrations (CT)) will be performed on Days 44 and 48. Semi-intensive PK sampling for RPT will be performed on day 78. Viral load will be measured at baseline (screening, week 0) and at weeks 7 and 24. Safety labs (complete blood count (CBC), urea and electrolytes (U\&E), and creatinine, and liver function tests (LFT)) will be obtained at baseline (screening, week 0), and weeks 4, 7, 12, 16, 20 and 24. Analysis will occur when 30 participants, in the case of twice daily DTG dosing, or 45 participants, in the case of once daily DTG dosing, have all completed the Week 24 visit.
Group 2a will occur following interim results from Group 1a, but may proceed without results from Group 1b.
Group 2b (n=24 or 16): In the case where we proceed with evaluating once daily DTG with 3HP in children less than 2 years of age, an additional 24 participants with suppressed viral load will be enrolled. In the case where we proceed with evaluating twice daily DTG dosing with 3HP, an additional 16 participants less than 2 years of age with suppressed viral load will be enrolled. Both groups would take dolutegravir once daily from days 1-28 (weeks 1-4). On day 28, semi-intensive PK sampling for dolutegravir will be performed (prior to any HP dose). On day 29 (week 5), participants will either continue to take once daily DTG or their daily weight-based DTG dose will be increased to twice daily (based on group 1a and group 1b data) and the first of the 12 HP weekly weight-based HP doses will be provided. Semi-intensive PK sampling for DTG will be performed on day 46 (3 days post third HP dose). Additional sparse PK sampling for dolutegravir (trough concentrations (CT)) will be performed on Days 44 and 48. Semi-intensive PK sampling for RPT will be performed on day 78. Viral load will be measured at baseline (screening, week 0) and at weeks 7 and 24. Safety labs (complete blood count (CBC), urea and electrolytes (U\&E), and creatinine, and liver function tests (LFT)) will be obtained at baseline (screening, week 0), and weeks 4, 7, 12, 16, 20 and 24. Analysis will occur when 16 participants, in the case of twice-daily DTG dosing, or 24 participants, in the case of once-daily DTG dosing, have all completed the Week 24 visit.
Group 2b will follow Group 1b and may or may not occur in parallel with Group 2a. This depends on the availability of dosing and a child-friendly formulation for 3HP in children 2 years and younger.
- Conditions
- Tuberculosis, HIV
- Being tested
- Dolutegravir, 3HP
- Keywords
- TB, 3HP, pharmacokinetic, rifapentine, isoniazid, dolutegravir
- Medical subject headings
- Tuberculosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DolutegravirDrug
Groups 1a/1b: Participants will take the FDA-approved weight-based DTG once daily + either TDF/FTC, TDF/3TC, ABC/3TC or AZT/3TC x 4 weeks. During HP treatment and for two weeks afterward, DTG dose will be increased to twice daily.
Participants will continue with the NRTI regimen they have previously tolerated, except where their age and weight allow them to transition from either AZT or ABC to TDF, as per South African National ART Guidelines. HLA-B*5701 screening will therefore not be performed, as children will be currently taking and tolerating an ABC-containing regimen at enrolment. If any clinically suspected hypersensitivity reaction to ABC is suspected by history, ABC will not be continued.
Groups 2a/2b: Participants will take weight-based DTG dosing twice or once daily, depending on the results of the modelled data for the Group 1a (for Group 2a) and/or Group 1b (for Group 2b) participants in the interim analysis.
3HPDrug
3HP Dosing is by Age and Weight Children 2-15 years of age: 10-15kg (P 300mg, H 300mg); 16-23kg (P 450mg, H 500mg); 24-30kg (P 600mg, H 600mg); 31-34kg (P 750mg, H 700mg). Children 15-17 years, >=30kg (P 900mg, H 900mg)
| Study group | Role | What they receive |
|---|---|---|
| Single Arm in 4 groups | Experimental | There will be four groups. Group 1a and Group 1b will provide semi-intensive PK data and safety monitoring to allow for comparison of twice-daily dolutegravir exposures together with HP vs. when DTG is given alone. Group 2a and Group 2b will provide semi-intensive PK data and safety monitoring for either twice-daily or once-daily dolutegravir together with HIV vs when DTG is given alone. All groups will provide safety and tolerability data, HIV virologic outcome data, and information about dolutegravir and rifapentine PK. Receives: Drug: Dolutegravir; Drug: 3HP |
What is being measured
The primary outcome is the main question the study is designed to answer.
PK sampling of Dolutegravir - ka parameter
Absorption rate constant (ka) in the presence or absence of once weekly HP (all groups)
Measured: PK sampling at Week 4 (Day 29) and Week 7 (Days 44, 46, and 48) to be reported at end of trial
PK sampling of Dolutegravir - Vd parameter
Volume of distribution in the presence or absence of once weekly HP (all groups)
Measured: PK sampling at Week 4 (Day 29) and Week 7 (Days 44, 46, and 48) to be reported at end of trial
PK sampling of Dolutegravir - Cl/F parameter
Oral clearance in the presence or absence of once weekly HP (all groups)
Measured: PK sampling at Week 4 (Day 29) and Week 7 (Days 44, 46, and 48) to be reported at end of trial
PK sampling of Dolutegravir - AUC parameter
Area under the plasma drug concentration-time curve in the presence or absence of once weekly HP (all groups)
Measured: PK sampling at Week 4 (Day 29) and Week 7 (Days 44, 46, and 48) to be reported at end of trial
PK sampling of Dolutegravir - Ctau parameter
Trough concentration in the presence or absence of once weekly HP (all groups)
Measured: PK sampling at Week 4 (Day 29) and Week 7 (Days 44, 46, and 48) to be reported at end of trial
Secondary outcomes (6)
Adverse Events
Grade 3 or higher adverse events (AE) (all groups)
Measured: Adverse events to be collected from Week 1 through Week 24, to be reported throughout the trial
HIV-1 RNA viral load
HIV-1 RNA viral load (copies/ml) (all groups)
Measured: HIV viral load to be measured at Screening, and Weeks 7 and 24, to be reported at end of trial
PK sampling of RPT - AUC parameter
Area under curve (AUC) (all groups)
Measured: PK sampling at Week 12 (Day 78) to be reported at end of trial
PK sampling of RPT - Cmax parameter
Maximum concentration (Cmax) (all groups)
Measured: PK sampling at Week 12 (Day 78) to be reported at end of trial
PK sampling of RPT - Ctau parameter
Trough concentration (Ctau) (all groups)
Measured: PK sampling at Week 12 (Day 78) to be reported at end of trial
DTG Dose selection
Dose options for DTG with once-weekly HP derived by simulation using nonlinear mixed effects models
Measured: Dose selection will be determined at the interim analysis to be conducted when all participants in Groups 1a and 1b have completed the Week 7 PK visit. Based upon these results, Groups 2a and 2b will receive DTG either once or twice daily.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Nov 2021
- Study start24 May 2023
- Primary completion4 Jul 2025
- Study completion31 Dec 2025 (estimated)
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.
- 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 1/2
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Single-arm, multi-center, Phase I/II clinical trial, in two groups. Individuals with HIV infection taking Efavirenz (EFV), nevirapine (NVP) or lopinavir/ritonavir (LPV/r) and two nucleoside reverse transcriptase inhibitors (NRTI) who have undetectable HIV viral load (\< 50 copies/mL) and an indication for TPT, will be switched to DTG with tenofovir/emtricitabine (TDF/FTC), tenofovir/lamivudine (TDF/3TC), abacavir/lamivudine (ABC/3TC) or zidovudine/lamivudine (AZT/3TC) in accordance with South African National HIV Guidelines. Groups 1 and 2 will receive weekly HP for 12 total doses starting 4 weeks after initiating DTG. Individuals who are on an existing DTG-based plus two NRTI ART regimen for at least four weeks (and have not received efavirenz, or nevirapine or lopinavir/ritonavir for at least four weeks) who have an undetectable HIV viral load may also participate.
- Masking
- None (open label)
- Enrolment
- 92 participants (estimated)
Sponsor and investigators
- Lead sponsor
- The Aurum Institute NPC
- Sponsor type
- University, hospital or other
- Collaborators
- Johns Hopkins University
- Responsible party
- Sponsor
- Investigators
- Nicole Salazar-Austin, Principal investigator, JHU SOM Ped Infectious Disease
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05122767
- Sponsor's protocol ID
- IRB00280272
- Acronym
- DOLPHIN KIDS
- Status last verified
- Dec 2025
- First submitted
- 9 Aug 2021
- Last updated
- 12 Dec 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety, Tolerability and Drug-drug Interactions of Short-course Treatment of Latent Tuberculosis Infection With High-dose Once-weekly Rifapentine and Isoniazid (3HP) Among Infants, Children and Adolescents Living With HIV Taking Dolutegravir-based Antiretroviral Treatment
- ClinicalTrials.gov ID
- NCT05122767
- Acronym / sponsor ID
- DOLPHIN KIDS / IRB00280272
- Conditions
- Tuberculosis, HIV
- Keywords
- TB, 3HP, pharmacokinetic, rifapentine, isoniazid, dolutegravir
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 92 participants (estimated)
- Lead sponsor
- The Aurum Institute NPCUniversity, hospital or other
- Collaborators
- Johns Hopkins University
- Study start
- 24 May 2023 (actual)
- Primary completion
- 4 Jul 2025 (actual)
- Study completion
- 31 Dec 2025 (estimated)
- First posted
- 17 Nov 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.
Single-arm, multi-center, Phase I/II clinical trial, in two groups. Individuals with HIV infection taking Efavirenz (EFV), nevirapine (NVP) or lopinavir/ritonavir (LPV/r) and two nucleoside reverse transcriptase inhibitors (NRTI) who have undetectable HIV viral load (VL) (< 50 copies/mL) and an indication for tuberculosis (TB) preventive treatment (TPT), will be switched to dolutegravir (DTG) with tenofovir/emtricitabine (TDF/FTC), tenofovir/lamivudine (TDF/3TC), abacavir/lamivudine (ABC/3TC) or zidovudine/lamivudine (AZT/3TC) in accordance with South African National HIV Guidelines. Groups 1 and 2 will receive weekly HP for 12 total doses starting 4 weeks after initiating DTG. Individuals who are on an existing DTG-based plus two NRTI antiretroviral therapy (ART) regimen for at least four weeks (and have not received efavirenz, or nevirapine or lopinavir/ritonavir for at least four weeks) who have an undetectable HIV viral load may also participate.
Detailed description
Group 1a (n=15): 15 participants aged 2-17 years of age will have suppressed viral load and take weight-based dosing of dolutegravir once daily with two nucleoside reverse transcriptase inhibitors (NRTIs) from Days 1-28. Semi-intensive pharmacokinetic (PK) sampling for dolutegravir will be performed on Day 28. Participants start twice-daily dolutegravir and will receive once-weekly rifapentine (RPT) and isoniazid (INH) (3HP) for 12 total doses beginning on Day 29. Semi-intensive PK sampling for dolutegravir will be performed on Day 46 (3 days after the 3rd dose of HP). Additional sparse PK sampling for dolutegravir (trough concentrations (CT)) will be performed on Days 44 and 48. Semi-intensive PK sampling for RPT will be performed on day 78. PK assessments will not be performed for isoniazid given that it's a well-studied drug in children. VL will be measured at baseline (week 0) and week 7 (after 3 doses of 3HP) and week 24 (8 weeks after the last dose of 3HP). Safety labs (complete blood count (CBC), urea and electrolytes (U\&E), creatinine, and liver function tests (LFT)) will be obtained at baseline (week 0), and weeks 4, 7, 12, 16, 20, and 24.
Interim analysis will occur when all Group 1a participants have completed the 7-week semi-intensive PK visit (HP week 3). Enrolment into Group 2a (but not group 1b) will commence once this interim analysis is complete. Enrolment into group 1b will not be paused during this interim analysis. The interim analysis will assess PK, safety, and VL data. PK data will be modeled to assess the appropriateness of studying once-daily DTG dosing with co-administration of 3HP. The subsequent 30-45 participants age 2-17 years of age in Group 2a will receive twice or once-daily dosing of DTG, respectively, depending on PK modeling results.
Group 1b (n=8 ): All participants less than 2 years of age with a suppressed viral load will take weight-based dosing of dolutegravir once daily with two nucleoside reverse transcriptase inhibitors (NRTIs) from Days 1-28. Semi-intensive PK sampling for dolutegravir will be performed on Day 28. Participants start twice-daily dolutegravir and will receive once-weekly HP for 12 total doses beginning on Day 29. Semi-intensive PK sampling for dolutegravir will be performed on Day 46 (3 days after the 3rd dose of HP). Additional sparse PK sampling for dolutegravir (trough concentrations (CT)) will be performed on Days 44 and 48. Semi-intensive PK sampling for RPT will be performed on day 78. PK assessments will not be performed for isoniazid given that it's a well-studied drug in children. VL will be measured at baseline (week 0) and weeks 7 and 24. Safety labs (complete blood count (CBC), urea and electrolytes (U\&E), creatinine, and liver function tests (LFT)) will be obtained at baseline (week 0), and weeks 4, 7, 12, 16, 20 and 24.
Interim analysis will occur when all Group 1b participants have completed the 7-week semi-intensive PK visit (HP week 3). Enrolment into group 2b (but not group 2a) will commence once this interim analysis is complete. Enrolment into group 2a will not be paused during this interim analysis. Interim analysis will assess PK, safety, and VL data. PK data will be modeled to assess the appropriateness of studying once-daily DTG dosing with co-administration of 3HP. The subsequent 16-24 participants in group 2b will receive twice or once-daily dosing of DTG, respectively, depending on population PK modeling results in this interim group.
Group 1b may or may not occur in parallel with Group 1a. This depends on the availability of dosing and a child-friendly formulation for 3HP in children 2 years and younger.
Group 2a (n=45 or 30): In the case where we proceed with evaluating once-daily DTG with 3HP in children 2-17 years of age, an additional 45 participants with suppressed viral load will be enrolled. In the case where we proceed with evaluating twice-daily DTG dosing with 3HP, an additional 30 participants with suppressed viral load will be enrolled. Both groups will take dolutegravir once daily from days 1-28 (weeks 1-4). On day 28, semi-intensive PK sampling for dolutegravir will be performed (prior to any HP dose). On day 29 (week 5), participants will either continue to take once daily DTG or their daily weight-based DTG dose will be increased to twice daily (based on group 1a data) and the first of the 12 HP weekly weight-based HP doses will be provided. Semi-intensive PK sampling for DTG will be performed on day 46 (2-4 days post third HP dose). Additional sparse PK sampling for dolutegravir (trough concentrations (CT)) will be performed on Days 44 and 48. Semi-intensive PK sampling for RPT will be performed on day 78. Viral load will be measured at baseline (screening, week 0) and at weeks 7 and 24. Safety labs (complete blood count (CBC), urea and electrolytes (U\&E), and creatinine, and liver function tests (LFT)) will be obtained at baseline (screening, week 0), and weeks 4, 7, 12, 16, 20 and 24. Analysis will occur when 30 participants, in the case of twice daily DTG dosing, or 45 participants, in the case of once daily DTG dosing, have all completed the Week 24 visit.
Group 2a will occur following interim results from Group 1a, but may proceed without results from Group 1b.
Group 2b (n=24 or 16): In the case where we proceed with evaluating once daily DTG with 3HP in children less than 2 years of age, an additional 24 participants with suppressed viral load will be enrolled. In the case where we proceed with evaluating twice daily DTG dosing with 3HP, an additional 16 participants less than 2 years of age with suppressed viral load will be enrolled. Both groups would take dolutegravir once daily from days 1-28 (weeks 1-4). On day 28, semi-intensive PK sampling for dolutegravir will be performed (prior to any HP dose). On day 29 (week 5), participants will either continue to take once daily DTG or their daily weight-based DTG dose will be increased to twice daily (based on group 1a and group 1b data) and the first of the 12 HP weekly weight-based HP doses will be provided. Semi-intensive PK sampling for DTG will be performed on day 46 (3 days post third HP dose). Additional sparse PK sampling for dolutegravir (trough concentrations (CT)) will be performed on Days 44 and 48. Semi-intensive PK sampling for RPT will be performed on day 78. Viral load will be measured at baseline (screening, week 0) and at weeks 7 and 24. Safety labs (complete blood count (CBC), urea and electrolytes (U\&E), and creatinine, and liver function tests (LFT)) will be obtained at baseline (screening, week 0), and weeks 4, 7, 12, 16, 20 and 24. Analysis will occur when 16 participants, in the case of twice-daily DTG dosing, or 24 participants, in the case of once-daily DTG dosing, have all completed the Week 24 visit.
Group 2b will follow Group 1b and may or may not occur in parallel with Group 2a. This depends on the availability of dosing and a child-friendly formulation for 3HP in children 2 years and younger.
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Single-arm, multi-center, Phase I/II clinical trial, in two groups. Individuals with HIV infection taking Efavirenz (EFV), nevirapine (NVP) or lopinavir/ritonavir (LPV/r) and two nucleoside reverse transcriptase inhibitors (NRTI) who have undetectable HIV viral load (< 50 copies/mL) and an indication for TPT, will be switched to DTG with tenofovir/emtricitabine (TDF/FTC), tenofovir/lamivudine (TDF/3TC), abacavir/lamivudine (ABC/3TC) or zidovudine/lamivudine (AZT/3TC) in accordance with South African National HIV Guidelines. Groups 1 and 2 will receive weekly HP for 12 total doses starting 4 weeks after initiating DTG. Individuals who are on an existing DTG-based plus two NRTI ART regimen for at least four weeks (and have not received efavirenz, or nevirapine or lopinavir/ritonavir for at least four weeks) who have an undetectable HIV viral load may also participate.
| Arm | Type | Receives |
|---|---|---|
| Single Arm in 4 groups | Experimental | Drug: Dolutegravir, Drug: 3HPThere will be four groups. Group 1a and Group 1b will provide semi-intensive PK data and safety monitoring to allow for comparison of twice-daily dolutegravir exposures together with HP vs. when DTG is given alone. Group 2a and Group 2b will provide semi-intensive PK data and safety monitoring for either twice-daily or once-daily dolutegravir together with HIV vs when DTG is given alone. All groups will provide safety and tolerability data, HIV virologic outcome data, and information about dolutegravir and rifapentine PK. |
Who may qualify
- Ages
- 3 months to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (4 listed)
- Age 3 months through 17 years
- Weight > 3 kg
- Documented HIV infection by DNA polymerase chain reaction (PCR) or plasma RNA-PCR if <18 months and by HIV-ELISA if 18 months and confirmed with a DNA PCR or RNA-PCR from an independent sample
- Undetectable HIV-1 viral load
Key exclusion criteria (17 listed)
- Confirmed or suspected TB disease (evidenced by symptoms and/or clinical exam findings and/or chest radiographic findings suggestive of TB, positive mycobacterial culture or molecular TB testing, or currently on TB treatment for active TB disease)
- Likely to move from the study area during the study period
- Known exposure to TB cases with known or suspected resistance to isoniazid or rifampicin in the source case
- TB treatment within the past year
- Prior completion of a TPT course without re-exposure to persons with infectious TB since TPT completion
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 |
|---|---|---|
| DolutegravirGroups 1a/1b: Participants will take the FDA-approved weight-based DTG once daily + either TDF/FTC, TDF/3TC, ABC/3TC or AZT/3TC x 4 weeks. During HP treatment and for two weeks afterward, DTG dose will be increased to twice daily. Participants will continue with the NRTI regimen they have previously tolerated, except where their age and weight allow them to transition from either AZT or ABC to TDF, as per South African National ART Guidelines. HLA-B*5701 screening will therefore not be performed, as children will be currently taking and tolerating an ABC-containing regimen at enrolment. If any clinically suspected hypersensitivity reaction to ABC is suspected by history, ABC will not be continued. Groups 2a/2b: Participants will take weight-based DTG dosing twice or once daily, depending on the results of the modelled data for the Group 1a (for Group 2a) and/or Group 1b (for Group 2b) participants in the interim analysis. | Drug | Single Arm in 4 groups |
| 3HP3HP Dosing is by Age and Weight Children 2-15 years of age: 10-15kg (P 300mg, H 300mg); 16-23kg (P 450mg, H 500mg); 24-30kg (P 600mg, H 600mg); 31-34kg (P 750mg, H 700mg). Children 15-17 years, >=30kg (P 900mg, H 900mg) | Drug | Single Arm in 4 groups |
Primary outcome
PK sampling of Dolutegravir - ka parameter
Time frame: PK sampling at Week 4 (Day 29) and Week 7 (Days 44, 46, and 48) to be reported at end of trial
Absorption rate constant (ka) in the presence or absence of once weekly HP (all groups)
PK sampling of Dolutegravir - Vd parameter
Time frame: PK sampling at Week 4 (Day 29) and Week 7 (Days 44, 46, and 48) to be reported at end of trial
Volume of distribution in the presence or absence of once weekly HP (all groups)
PK sampling of Dolutegravir - Cl/F parameter
Time frame: PK sampling at Week 4 (Day 29) and Week 7 (Days 44, 46, and 48) to be reported at end of trial
Oral clearance in the presence or absence of once weekly HP (all groups)
PK sampling of Dolutegravir - AUC parameter
Time frame: PK sampling at Week 4 (Day 29) and Week 7 (Days 44, 46, and 48) to be reported at end of trial
Area under the plasma drug concentration-time curve in the presence or absence of once weekly HP (all groups)
PK sampling of Dolutegravir - Ctau parameter
Time frame: PK sampling at Week 4 (Day 29) and Week 7 (Days 44, 46, and 48) to be reported at end of trial
Trough concentration in the presence or absence of once weekly HP (all groups)
6 secondary outcomes
Adverse Events
Time frame: Adverse events to be collected from Week 1 through Week 24, to be reported throughout the trial
HIV-1 RNA viral load
Time frame: HIV viral load to be measured at Screening, and Weeks 7 and 24, to be reported at end of trial
PK sampling of RPT - AUC parameter
Time frame: PK sampling at Week 12 (Day 78) to be reported at end of trial
PK sampling of RPT - Cmax parameter
Time frame: PK sampling at Week 12 (Day 78) to be reported at end of trial
PK sampling of RPT - Ctau parameter
Time frame: PK sampling at Week 12 (Day 78) to be reported at end of trial
DTG Dose selection
Time frame: Dose selection will be determined at the interim analysis to be conducted when all participants in Groups 1a and 1b have completed the Week 7 PK visit. Based upon these results, Groups 2a and 2b will receive DTG either once or twice daily.
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 12 Dec 2025.
- Individual participant dataSharing planned: No
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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.
Nicole Salazar-Austin principal investigator
JHU SOM Ped Infectious Disease
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Dolutegravir and 3HP in people with Tuberculosis and HIV, run by The Aurum Institute NPC at 2 sites in South Africa.
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 17 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: under way, not looking for participants, as of the sponsor's last update on 12 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in South Africa. 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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
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?
PK sampling of Dolutegravir - ka parameter (time frame: PK sampling at Week 4 (Day 29) and Week 7 (Days 44, 46, and 48) to be reported at end of trial). The study lists 5 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 12 Dec 2025; AzTrials last refreshed its copy on 8 Nov 2026.