Respiratory Tract InfectionsPhase 1/2IMPAACT4TBNCT03435146
Safety Tolerability DDI Short Course Treatment of LTBI Infection With High-dose Rifapentine and Isoniazid or Standard Isoniazid Preventive Therapy in HIV+ Patients (DOLPHIN & DOLPHIN TOO)
A Phase 1/2 study testing 3HP plus DTG +2NRTIs in people with Respiratory Tract Infections and HIV Infections, run by The Aurum Institute NPC at 1 site in South Africa.
Trial summary
Single-arm, single-center, Phase I/II clinical trial, in four groups. Individuals with HIV infection taking Efavirenz (EFV) and two nucleoside reverse transcriptase inhibitors (NRTI) who have undetectable (Groups 1 and 2) or detectable (Group 3 and 4) HIV viral load and an indication for TPT, will be switched to DTG… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Respiratory Tract Infections, HIV Infections
- What is being tested?
- 3HP plus DTG +2NRTIs
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 135 participants
- Where
- 1 siteSouth Africa
- Study dates
- 18 Jan 2018to 7 Dec 2022
- Phase
- Phase 1/2
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age > 18 years
- Weight > 50 kg
- Documented HIV infection*
- At least 8 weeks of HIV treatment with efavirenz or dolutegravir plus two NRTI, or ART treatment naïve, depending upon the enrolling treatment Group
- Undetectable or detectable HIV-1 viral load, depending upon the enrolling treatment Group
Who cannot join
- Confirmed or suspected 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
- TB preventive therapy within the last year
- Sensitivity or intolerance to isoniazid or rifamycins
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- On nevirapine, etravirine, rilpivirine, PI-based, or raltegravir-containing ART regimens
- Suspected acute hepatitis or known chronic liver disease; severe hepatic impairment (Class C or greater) as determined by Child Pugh classification
- ALT≥ 3 times the upper limit of normal (ULN)
- Total bilirubin ≥ 2.5 times the ULN
- Absolute neutrophil count (ANC) ≤ 750 cells/mm3
- Creatinine clearance < 50 ml/min
- Pregnancy or breastfeeding
- Women of childbearing potential who are unable or unwilling to use contraception
- Self-reported alcohol use exceeding 28 units per week for men, or 21 units for women
- Karnofsky status < 80
- On prohibited medications e.g. dofetilide (see Appendix 1)
- Known porphyria
Trial locations and contacts
1 site in 1 country.
South Africa1 site
The Aurum Institute: Tembisa Clinical Research Centre
Tembisa, Gauteng, 1736
About this study
Official title: Safety, Tolerability, and Drug-drug Interactions of Short-course Treatment of Latent Tuberculosis Infection With High-dose Rifapentine and Isoniazid or Standard Isoniazid Preventative Therapy Among HIV-infected Patients Taking Dolutegravir-based Antiretroviral Treatment
Single-arm, single-center, Phase I/II clinical trial, in four groups. Individuals with HIV infection taking Efavirenz (EFV) and two nucleoside reverse transcriptase inhibitors (NRTI) who have undetectable (Groups 1 and 2) or detectable (Group 3 and 4) HIV viral load and an indication for TPT, will be switched to DTG with tenofovir/emtricitabine (Groups 1 and 2) or lamivudine/tenofovir (Groups 3 and 4). Group 1 and 2 will receive weekly HP for 12 total doses starting 8 weeks after initiating DTG. Individuals who are on an existing DTG-based plus two NRTI ART regimen for at least eight weeks (and have not received efavirenz or nevirapine for at least two months) who have an undetectable HIV viral load may also participate. Individuals with HIV infection who are ART treatment naïve at any HIV viral load level and have an indication for TPT will start DTG and be enrolled to receive standard IPT (Group 3) or HP (Group 4) initiated at the same time as DTG. Group 3 and 4 will be enrolled after follow up of Group 1 and 2 has been completed.
Read the detailed description
Group 1 (n=30): The first 12 participants (Group 1A) will take dolutegravir 50 milligrams (mg) once daily (with tenofovir/emtricitabine) from Days 1-57. Semi-intensive PK sampling for dolutegravir will be performed on Day 57. Participants will continue once-daily dolutegravir and will receive once-weekly HP for 12 total doses beginning on Day 58. Semi-intensive PK sampling for dolutegravir will be performed on Day 72 (with the 3rd dose of HP) and Day 108 (following the 8th dose of HP). Trough concentrations (CT) will be measured on Days 59, 74, and 78. PK assessments will be performed at weeks 9 and 11 for rifapentine and at week 11 for isoniazid. VL will be measured at baseline and weeks 11 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, and weeks 9, 11, 13, 16, 20 and 24.
After the 12 Group 1A participants have completed the second semi-intensive PK visit, an interim PK, safety, and VL assessment will be performed to ensure that the 50 mg once daily dose is safe and meets PK targets. The subsequent 18 participants in Group 1 (Group 1B) will receive either dolutegravir 50 mg or a higher dose of dolutegravir, if dose adjustment is required (e.g. dolutegravir 50 mg twice daily just on HP dosing days, dolutegravir 50 mg twice daily seven days a week, etc.) A second interim evaluation focused on PK will occur after all Group 1B participants have completed the Week 11 semi-intensive PK visit. This evaluation will include all PK data from Group 1A, who will have completed their Week 16 semi-intensive PK visit plus PK data from Group 1B up to and including the Week 11 semi-intensive PK visit.
A third interim evaluation focused on safety and virologic response will occur after all participants (Groups 1A, 1B, and 2) have completed the Week 11 visit. This evaluation will include all safety data and HIV viral load information collected up until that point from all participants.
Group 2 (n=30): These participants will receive dolutegravir and HP at the same doses and dose schedule as the participants in Group 1B. They will undergo safety assessments at baseline and weeks 9, 11, 13, 16, 20 and 24; HIV VL assessments will be performed at baseline and weeks 11 and 24. Sparse (trough) PK samples for dolutegravir will be collected on two occasions.
Group 3 (n=25): The next 25 participants who are ART treatment naïve will start dolutegravir 50 milligrams (mg) once daily (with tenofovir/lamivudine on study Day 0. Sparse PK sampling for trough concentrations (CT) of dolutegravir will be performed on Day 1 (24 hours after taking the first dose of DTG, and before taking the first dose of standard isoniazid). Sparse PK sampling for trough concentrations (CT) of dolutegravir will be performed on Day 24 (Week 3), to parallel 721 hours after the 3rd dose of HP. The final sparse PK sampling for trough concentrations (CT) of dolutegravir will be performed on Day 59 (Week 8), to parallel 721 hours after the 8th dose of HP. HIV VL will be measured at screening, and Weeks 3, 8, 12, 16, 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. Creatinine will be repeated at Weeks 2, 4, 8, 12, 16 and 24 and LFTs will be repeated at weeks 4, 8, and 12.
Group 4 (n=50): After Group 3 is fully enrolled, another group of 50 participants who are ART treatment naïve will start dolutegravir 50 milligrams (mg) once daily (with tenofovir/lamivudine) on Day 0. They will begin TPT with once weekly HP the day after starting DTG, on Day 1. Sparse PK sampling for trough concentrations (CT) dolutegravir will be performed on Day 1 (24 hours after the first dose of DTG, before the first dose of HP). Sparse PK sampling for trough concentrations (CT) of dolutegravir will be performed on Day 24 (721 hours after the third dose of HP). Sparse PK sampling for trough concentrations (CT) of dolutegravir will be performed on Day 59 (721 hours after the eighth dose of HP). HIV VL will be measured at screening, and Weeks 3, 8, 12, 16, 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. Creatinine will be repeated at Weeks 2, 4, 8, 12, 16, and 24, and LFTs will be repeated at weeks 4, 8, and 12.
1 (+/- 24 hours)
- Conditions
- Respiratory Tract Infections, HIV Infections
- Being tested
- 3HP plus DTG +2NRTIs
- Keywords
- 3HP, LTBI, IMPAACT4TB, DDI, Pharmacokinetics, Dolutegravir
- Medical subject headings
- Respiratory Tract Infections, HIV Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
3HP plus DTG +2NRTIsCombination product
- HIV treatment: DTG will be dosed as described above and will be given with daily TDF/FTC (Groups 1 and 2) or with TDF/3TC (Groups 3 and 4).
- LTBI treatment: 3HP will be given once-weekly for a total of 12 doses, with doses as follows:
Rifapentine: 900 mg; Isoniazid: 900 mg (Groups 1,2 and 4) Isoniazid at standard of care dosing (Group 3)
| Study group | Role | What they receive |
|---|---|---|
| Groups 1,2,3 and 4 | Experimental | Group 1: The first 12 participants (Group 1A) will undergo semi-intensive PK sampling and will be key to determining whether an increased dosing of dolutegravir is required in groups 1B. Group 1B will receive dolutegravir at the new dose (if applicable) and will also undergo semi-intensive PK sampling. All will undergo safety and HIV VL assessments.
3HP plus DTG +2NRTIs
Group 2: The next 30 (Group 2) will receive dolutegravir at the new dose and will only have sparse PK sampling. All will undergo safety and HIV VL assessments.
3HP plus DTG +2NRTIs
Group 3: The next 25 (Group 3) will receive dolutegravir at the same dose as Group 2 and will only have sparse PK sampling. All will undergo safety and HIV VL assessments.
IPT plus DTG +2NRTIs
Group 4: The next 50 (Group 4) will receive dolutegravir at the same dose as Group 2 and will only have sparse PK sampling. All will undergo safety and HIV VL assessments.
3HP plus DTG +2NRTIs Receives: Combination Product: 3HP plus DTG +2NRTIs |
What is being measured
The primary outcome is the main question the study is designed to answer.
PK sampling of Dolutegravir - Ctau
Trough concentration in the presence or absence of once weekly HP
Measured: PK sampling at Week 9 (Group 1), Week 11 (Groups 1 and 2) and Week 16 (Groups 1 and 2); Day 1 (Groups 3 and 4), Week 3 (Groups 3 and 4) and Week 8 (Groups 3 and 4) to be reported at end of trial
PK sampling of Dolutegravir - AUC parameter
Daily area under curve (AUC) in the presence or absence of once weekly HP
Measured: PK sampling at Week 9 (Group 1), Week 11 (Groups 1 and 2) and Week 16 (Groups 1 and 2); Day 1 (Groups 3 and 4), Week 3 (Groups 3 and 4) and Week 8 (Groups 3 and 4) to be reported at end of trial
PK sampling of Dolutegravir - Cmin parameter
Minimum concentration (Cmin) in the presence or absence of once weekly HP
Measured: PK sampling at Week 9 (Group 1), Week 11 (Groups 1 and 2) and Week 16 (Groups 1 and 2); Day 1 (Groups 3 and 4), Week 3 (Groups 3 and 4) and Week 8 (Groups 3 and 4) to be reported at end of trial
Adverse Events (Primary)
Grade 3 or higher adverse events (AE)
Measured: Adverse events to be collected from Week 1 through Week 24, to be reported throughout the trial
Secondary outcomes (8)
HIV-1 RNA viral load
HIV-1 RNA viral load (copies/ml)
Measured: HIV viral load to be measured in Groups 1 and 2 at screening, weeks 11 and 24; and in Groups 3 and 4 at screening and weeks 3, 8, 12 and 24, to be reported at end of trial
PK sampling of RPT - AUC parameter
Area under curve (AUC).
Measured: PK sampling at Weeks 9 and 11 (Group 1); and Week 11 (Group 2), Day 1 (Groups 3 and 4), Week 3 (Groups 3 and 4) and Week 8 (Groups 3 and 4) to be reported at end of trial
PK sampling of RPT - Cmax parameter
Maximum concentration (Cmax).
Measured: PK sampling at Weeks 9 and 11 (Group 1); and Week 11 (Group 2), Day 1 (Groups 3 and 4), Week 3 (Groups 3 and 4) and Week 8 (Groups 3 and 4) to be reported at end of trial
PK sampling of RPT - Cmin parameter
Minimum concentration (Cmax).
Measured: PK sampling at Weeks 9 and 11 (Group 1); and Week 11 (Group 2), Day 1 (Groups 3 and 4), Week 3 (Groups 3 and 4) and Week 8 (Groups 3 and 4) to be reported at end of trial
PK sampling of INH - AUC parameter
Area under curve (AUC). NAT 2 acetylator status to be taken into account
Measured: PK sampling at Week 11(Group 1 only), to be reported at end of trial
PK sampling of INH - Cmax parameter
Maximum concentration (Cmax). NAT 2 acetylator status to be taken into account
Measured: PK sampling at Week 11(Group 1 only), to be reported at end of trial
PK sampling of INH - Cmin parameter
Minimum concentration (Cmin). NAT 2 acetylator status to be taken into account
Measured: PK sampling at Week 11(Group 1 only), 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: Post Group 1A. Dose will be selected once Group 1a participants' PK data have been analyzed. The dolutegravir dose may be adjusted according to PK results. If warranted, the revised dose will be administered to Groups 1B and 2.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Feb 2018
- Study start18 Jan 2018
- Primary completion7 Dec 2022
- Study completion7 Dec 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Respiratory Tract InfectionsStudies 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
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Model description
- Group 1A:12 ppts will take DTG 50mg/TDF/FTC once daily + once weekly HP for 12 weeks. Semi-intensive PK for DTG,RPT,INH will be collected per protocol.An interim PK, safety,and HIV VL assessment will be performed to ensure that DTG 50mg once daily is safe and meets PK targets.Group 1B:18 ppts will receive either DTG 50mg or dose adjusted DTG + once weekly HP. Semi-intensive PK for DTG,RPT,INH will be collected per protocol.Group 2: 30 ppts will receive DTG at the same dose and frequency as Group 1B. Sparse PK for DTG, safety labs and HIV VL will be measured per protocol.Group 3: 25 ppts who are HIV tx naive will start DTG 50mg/TDF/3TC daily as a FDC tablet + standard of care isoniazid preventive therapy. ART and IPT will start together. Sparse PK for DTG will be collected per protocol.Group 4: 50 ppts who are HIV treatment naive will start DTG 50mg/TDF/3TC daily as a FDC tablet + weekly HP for 12 weeks. ART and 3HP will start together. Sparse PK for DTG will be collected per protocol.
- Masking
- None (open label)
- Enrolment
- 135 participants (actual)
Sponsor and investigators
- Lead sponsor
- The Aurum Institute NPC
- Sponsor type
- University, hospital or other
- Collaborators
- Johns Hopkins University, University of California
- Responsible party
- Sponsor
- Investigators
- Gavin J Churchyard, MBBCh PhD, Principal investigator, Global CEO: The Aurum Institute, NPC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03435146
- Sponsor's protocol ID
- 3HP DTG AUR1-6-212 IMPAACT4TB
- Acronym
- IMPAACT4TB
- Status last verified
- Jan 2023
- First submitted
- 21 Aug 2017
- Last updated
- 2 Feb 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: To be shared amongst the collaborators on shared database when study starts and is complete. Results will be disseminated via conferences and publication by scientific peer reviewed journal(s)
Publications
Weld ED, Beattie T, Moodley J, Mapendere M, Salles I, Solans BP, Nonyane BAS, Wiesner L, Nielson T, Edward VA, Chihota V, Savic RM, Dooley KE, Chaisson RE, Churchyard GJ; DOLPHIN-TOO Study Team; Unitaid IMPAACT4TB Research Group. Simultaneous initiation of dolutegravir-based antiretroviral therapy and once-weekly rifapentine and isoniazid for tuberculosis prevention in antiretroviral-naive people with HIV: an open-label, non-randomised, phase 1/2 trial. Lancet HIV. 2025 Jun;12(6):e428-e439. doi: 10.1016/S2352-3018(25)00002-5. Epub 2025 May 8.
PubMed 40349709Jarrett RT, van der Heijden Y, Shotwell MS, Chihota V, Marzinke MA, Chaisson RE, Dooley KE, Churchyard GJ. High Isoniazid Exposures When Administered with Rifapentine Once Weekly for Latent Tuberculosis in Individuals with Human Immunodeficiency Virus. Antimicrob Agents Chemother. 2023 Feb 16;67(2):e0129722. doi: 10.1128/aac.01297-22. Epub 2023 Jan 9.
PubMed 36622148Dooley KE, Savic R, Gupte A, Marzinke MA, Zhang N, Edward VA, Wolf L, Sebe M, Likoti M, Fyvie MJ, Shibambo I, Beattie T, Chaisson RE, Churchyard GJ; DOLPHIN Study Team. Once-weekly rifapentine and isoniazid for tuberculosis prevention in patients with HIV taking dolutegravir-based antiretroviral therapy: a phase 1/2 trial. Lancet HIV. 2020 Jun;7(6):e401-e409. doi: 10.1016/S2352-3018(20)30032-1. Epub 2020 Mar 30.
PubMed 32240629
Study at a glance
From the registry record, last updated by the sponsor on 2 Feb 2023. 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 Rifapentine and Isoniazid or Standard Isoniazid Preventative Therapy Among HIV-infected Patients Taking Dolutegravir-based Antiretroviral Treatment
- ClinicalTrials.gov ID
- NCT03435146
- Acronym / sponsor ID
- IMPAACT4TB / 3HP DTG AUR1-6-212 IMPAACT4TB
- Conditions
- Respiratory Tract Infections, HIV Infections
- Keywords
- 3HP, LTBI, IMPAACT4TB, DDI, Pharmacokinetics, Dolutegravir
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 135 participants (actual)
- Lead sponsor
- The Aurum Institute NPCUniversity, hospital or other
- Collaborators
- Johns Hopkins University, University of California
- Study start
- 18 Jan 2018 (actual)
- Primary completion
- 7 Dec 2022 (actual)
- Study completion
- 7 Dec 2022 (actual)
- First posted
- 15 Feb 2018 (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, single-center, Phase I/II clinical trial, in four groups. Individuals with HIV infection taking Efavirenz (EFV) and two nucleoside reverse transcriptase inhibitors (NRTI) who have undetectable (Groups 1 and 2) or detectable (Group 3 and 4) HIV viral load and an indication for TPT, will be switched to DTG with tenofovir/emtricitabine (Groups 1 and 2) or lamivudine/tenofovir (Groups 3 and 4). Group 1 and 2 will receive weekly HP for 12 total doses starting 8 weeks after initiating DTG. Individuals who are on an existing DTG-based plus two NRTI ART regimen for at least eight weeks (and have not received efavirenz or nevirapine for at least two months) who have an undetectable HIV viral load may also participate. Individuals with HIV infection who are ART treatment naïve at any HIV viral load level and have an indication for TPT will start DTG and be enrolled to receive standard IPT (Group 3) or HP (Group 4) initiated at the same time as DTG. Group 3 and 4 will be enrolled after follow up of Group 1 and 2 has been completed.
Detailed description
Group 1 (n=30): The first 12 participants (Group 1A) will take dolutegravir 50 milligrams (mg) once daily (with tenofovir/emtricitabine) from Days 1-57. Semi-intensive PK sampling for dolutegravir will be performed on Day 57. Participants will continue once-daily dolutegravir and will receive once-weekly HP for 12 total doses beginning on Day 58. Semi-intensive PK sampling for dolutegravir will be performed on Day 72 (with the 3rd dose of HP) and Day 108 (following the 8th dose of HP). Trough concentrations (CT) will be measured on Days 59, 74, and 78. PK assessments will be performed at weeks 9 and 11 for rifapentine and at week 11 for isoniazid. VL will be measured at baseline and weeks 11 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, and weeks 9, 11, 13, 16, 20 and 24.
After the 12 Group 1A participants have completed the second semi-intensive PK visit, an interim PK, safety, and VL assessment will be performed to ensure that the 50 mg once daily dose is safe and meets PK targets. The subsequent 18 participants in Group 1 (Group 1B) will receive either dolutegravir 50 mg or a higher dose of dolutegravir, if dose adjustment is required (e.g. dolutegravir 50 mg twice daily just on HP dosing days, dolutegravir 50 mg twice daily seven days a week, etc.) A second interim evaluation focused on PK will occur after all Group 1B participants have completed the Week 11 semi-intensive PK visit. This evaluation will include all PK data from Group 1A, who will have completed their Week 16 semi-intensive PK visit plus PK data from Group 1B up to and including the Week 11 semi-intensive PK visit.
A third interim evaluation focused on safety and virologic response will occur after all participants (Groups 1A, 1B, and 2) have completed the Week 11 visit. This evaluation will include all safety data and HIV viral load information collected up until that point from all participants.
Group 2 (n=30): These participants will receive dolutegravir and HP at the same doses and dose schedule as the participants in Group 1B. They will undergo safety assessments at baseline and weeks 9, 11, 13, 16, 20 and 24; HIV VL assessments will be performed at baseline and weeks 11 and 24. Sparse (trough) PK samples for dolutegravir will be collected on two occasions.
Group 3 (n=25): The next 25 participants who are ART treatment naïve will start dolutegravir 50 milligrams (mg) once daily (with tenofovir/lamivudine on study Day 0. Sparse PK sampling for trough concentrations (CT) of dolutegravir will be performed on Day 1 (24 hours after taking the first dose of DTG, and before taking the first dose of standard isoniazid). Sparse PK sampling for trough concentrations (CT) of dolutegravir will be performed on Day 24 (Week 3), to parallel 721 hours after the 3rd dose of HP. The final sparse PK sampling for trough concentrations (CT) of dolutegravir will be performed on Day 59 (Week 8), to parallel 721 hours after the 8th dose of HP. HIV VL will be measured at screening, and Weeks 3, 8, 12, 16, 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. Creatinine will be repeated at Weeks 2, 4, 8, 12, 16 and 24 and LFTs will be repeated at weeks 4, 8, and 12.
Group 4 (n=50): After Group 3 is fully enrolled, another group of 50 participants who are ART treatment naïve will start dolutegravir 50 milligrams (mg) once daily (with tenofovir/lamivudine) on Day 0. They will begin TPT with once weekly HP the day after starting DTG, on Day 1. Sparse PK sampling for trough concentrations (CT) dolutegravir will be performed on Day 1 (24 hours after the first dose of DTG, before the first dose of HP). Sparse PK sampling for trough concentrations (CT) of dolutegravir will be performed on Day 24 (721 hours after the third dose of HP). Sparse PK sampling for trough concentrations (CT) of dolutegravir will be performed on Day 59 (721 hours after the eighth dose of HP). HIV VL will be measured at screening, and Weeks 3, 8, 12, 16, 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. Creatinine will be repeated at Weeks 2, 4, 8, 12, 16, and 24, and LFTs will be repeated at weeks 4, 8, and 12.
1 (+/- 24 hours)
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Group 1A:12 ppts will take DTG 50mg/TDF/FTC once daily + once weekly HP for 12 weeks. Semi-intensive PK for DTG,RPT,INH will be collected per protocol.An interim PK, safety,and HIV VL assessment will be performed to ensure that DTG 50mg once daily is safe and meets PK targets.Group 1B:18 ppts will receive either DTG 50mg or dose adjusted DTG + once weekly HP. Semi-intensive PK for DTG,RPT,INH will be collected per protocol.Group 2: 30 ppts will receive DTG at the same dose and frequency as Group 1B. Sparse PK for DTG, safety labs and HIV VL will be measured per protocol.Group 3: 25 ppts who are HIV tx naive will start DTG 50mg/TDF/3TC daily as a FDC tablet + standard of care isoniazid preventive therapy. ART and IPT will start together. Sparse PK for DTG will be collected per protocol.Group 4: 50 ppts who are HIV treatment naive will start DTG 50mg/TDF/3TC daily as a FDC tablet + weekly HP for 12 weeks. ART and 3HP will start together. Sparse PK for DTG will be collected per protocol.
| Arm | Type | Receives |
|---|---|---|
| Groups 1,2,3 and 4 | Experimental | Combination Product: 3HP plus DTG +2NRTIsGroup 1: The first 12 participants (Group 1A) will undergo semi-intensive PK sampling and will be key to determining whether an increased dosing of dolutegravir is required in groups 1B. Group 1B will receive dolutegravir at the new dose (if applicable) and will also undergo semi-intensive PK sampling. All will undergo safety and HIV VL assessments. 3HP plus DTG +2NRTIs Group 2: The next 30 (Group 2) will receive dolutegravir at the new dose and will only have sparse PK sampling. All will undergo safety and HIV VL assessments. 3HP plus DTG +2NRTIs Group 3: The next 25 (Group 3) will receive dolutegravir at the same dose as Group 2 and will only have sparse PK sampling. All will undergo safety and HIV VL assessments. IPT plus DTG +2NRTIs Group 4: The next 50 (Group 4) will receive dolutegravir at the same dose as Group 2 and will only have sparse PK sampling. All will undergo safety and HIV VL assessments. 3HP plus DTG +2NRTIs |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Age > 18 years
- Weight > 50 kg
- Documented HIV infection*
- At least 8 weeks of HIV treatment with efavirenz or dolutegravir plus two NRTI, or ART treatment naïve, depending upon the enrolling treatment Group
- Undetectable or detectable HIV-1 viral load, depending upon the enrolling treatment Group
Key exclusion criteria (18 listed)
- Confirmed or suspected 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
- TB preventive therapy within the last year
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 |
|---|---|---|
| 3HP plus DTG +2NRTIs* HIV treatment: DTG will be dosed as described above and will be given with daily TDF/FTC (Groups 1 and 2) or with TDF/3TC (Groups 3 and 4). * LTBI treatment: 3HP will be given once-weekly for a total of 12 doses, with doses as follows: Rifapentine: 900 mg; Isoniazid: 900 mg (Groups 1,2 and 4) Isoniazid at standard of care dosing (Group 3) | Combination product | Groups 1,2,3 and 4 |
Primary outcome
PK sampling of Dolutegravir - Ctau
Time frame: PK sampling at Week 9 (Group 1), Week 11 (Groups 1 and 2) and Week 16 (Groups 1 and 2); Day 1 (Groups 3 and 4), Week 3 (Groups 3 and 4) and Week 8 (Groups 3 and 4) to be reported at end of trial
Trough concentration in the presence or absence of once weekly HP
PK sampling of Dolutegravir - AUC parameter
Time frame: PK sampling at Week 9 (Group 1), Week 11 (Groups 1 and 2) and Week 16 (Groups 1 and 2); Day 1 (Groups 3 and 4), Week 3 (Groups 3 and 4) and Week 8 (Groups 3 and 4) to be reported at end of trial
Daily area under curve (AUC) in the presence or absence of once weekly HP
PK sampling of Dolutegravir - Cmin parameter
Time frame: PK sampling at Week 9 (Group 1), Week 11 (Groups 1 and 2) and Week 16 (Groups 1 and 2); Day 1 (Groups 3 and 4), Week 3 (Groups 3 and 4) and Week 8 (Groups 3 and 4) to be reported at end of trial
Minimum concentration (Cmin) in the presence or absence of once weekly HP
Adverse Events (Primary)
Time frame: Adverse events to be collected from Week 1 through Week 24, to be reported throughout the trial
Grade 3 or higher adverse events (AE)
8 secondary outcomes
HIV-1 RNA viral load
Time frame: HIV viral load to be measured in Groups 1 and 2 at screening, weeks 11 and 24; and in Groups 3 and 4 at screening and weeks 3, 8, 12 and 24, to be reported at end of trial
PK sampling of RPT - AUC parameter
Time frame: PK sampling at Weeks 9 and 11 (Group 1); and Week 11 (Group 2), Day 1 (Groups 3 and 4), Week 3 (Groups 3 and 4) and Week 8 (Groups 3 and 4) to be reported at end of trial
PK sampling of RPT - Cmax parameter
Time frame: PK sampling at Weeks 9 and 11 (Group 1); and Week 11 (Group 2), Day 1 (Groups 3 and 4), Week 3 (Groups 3 and 4) and Week 8 (Groups 3 and 4) to be reported at end of trial
PK sampling of RPT - Cmin parameter
Time frame: PK sampling at Weeks 9 and 11 (Group 1); and Week 11 (Group 2), Day 1 (Groups 3 and 4), Week 3 (Groups 3 and 4) and Week 8 (Groups 3 and 4) to be reported at end of trial
PK sampling of INH - AUC parameter
Time frame: PK sampling at Week 11(Group 1 only), to be reported at end of trial
PK sampling of INH - Cmax parameter
Time frame: PK sampling at Week 11(Group 1 only), to be reported at end of trial
PK sampling of INH - Cmin parameter
Time frame: PK sampling at Week 11(Group 1 only), to be reported at end of trial
DTG Dose selection
Time frame: Post Group 1A. Dose will be selected once Group 1a participants' PK data have been analyzed. The dolutegravir dose may be adjusted according to PK results. If warranted, the revised dose will be administered to Groups 1B and 2.
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 2 Feb 2023.
- Derived from this study: PubMed 40349709Weld ED, Beattie T, Moodley J, Mapendere M, Salles I, Solans BP, Nonyane BAS, Wiesner L, Nielson T, Edward VA, Chihota V, Savic RM, Dooley KE, Chaisson RE, Churchyard GJ; DOLPHIN-TOO Study Team; Unitaid IMPAACT4TB Research Group. Simultaneous initiation of dolutegravir-based antiretroviral therapy and once-weekly rifapentine and isoniazid for tuberculosis prevention in antiretroviral-naive people with HIV: an open-label, non-randomised, phase 1/2 trial. Lancet HIV. 2025 Jun;12(6):e428-e439. doi: 10.1016/S2352-3018(25)00002-5. Epub 2025 May 8.
- Derived from this study: PubMed 36622148Jarrett RT, van der Heijden Y, Shotwell MS, Chihota V, Marzinke MA, Chaisson RE, Dooley KE, Churchyard GJ. High Isoniazid Exposures When Administered with Rifapentine Once Weekly for Latent Tuberculosis in Individuals with Human Immunodeficiency Virus. Antimicrob Agents Chemother. 2023 Feb 16;67(2):e0129722. doi: 10.1128/aac.01297-22. Epub 2023 Jan 9.
- Derived from this study: PubMed 32240629Dooley KE, Savic R, Gupte A, Marzinke MA, Zhang N, Edward VA, Wolf L, Sebe M, Likoti M, Fyvie MJ, Shibambo I, Beattie T, Chaisson RE, Churchyard GJ; DOLPHIN Study Team. Once-weekly rifapentine and isoniazid for tuberculosis prevention in patients with HIV taking dolutegravir-based antiretroviral therapy: a phase 1/2 trial. Lancet HIV. 2020 Jun;7(6):e401-e409. doi: 10.1016/S2352-3018(20)30032-1. Epub 2020 Mar 30.
- Individual participant dataSharing planned: Yes. To be shared amongst the collaborators on shared database when study starts and is complete. Results will be disseminated via conferences and publication by scientific peer reviewed journal(s)
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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.
Gavin J Churchyard, MBBCh PhD principal investigator
Global CEO: The Aurum Institute, NPC
1 site 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 3HP plus DTG +2NRTIs in people with Respiratory Tract Infections and HIV Infections, run by The Aurum Institute NPC at 1 site 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 5 inclusion and 18 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 2 Feb 2023. 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 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?
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?
PK sampling of Dolutegravir - Ctau (time frame: PK sampling at Week 9 (Group 1), Week 11 (Groups 1 and 2) and Week 16 (Groups 1 and 2); Day 1 (Groups 3 and 4), Week 3 (Groups 3 and 4) and Week 8 (Groups 3 and 4) to be reported at end of trial). 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?
On the ClinicalTrials.gov record for NCT03435146, which also lists 3 linked publications.
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 2 Feb 2023.