HIV SeropositivityPhase 41 to 3NCT05118490
Comparing Treatment Completion Of Daily Rifapentine & Isoniazid For One Month (1HP) To Weekly High Dose Rifapentine & Isoniazid For 3 Months (3HP) In Persons Living With HIV and in Household Contacts of Recently Diagnosed Tuberculosis Patients
A Phase 4 study testing Daily rifapentine and isoniazid for 4 weeks and Weekly rifapentine and isoniazid for 12 weeks in people with HIV Seropositivity and Tuberculosis, run by The Aurum Institute NPC at 4 sites in 4 countries.
Trial summary
A multicenter, randomized, stratified, open-label, phase IV trial among HIV-positive persons (PLHIV) on antiretroviral therapy (ART), or HIV-negative household contacts of patients with rifampicin-sensitive pulmonary tuberculosis (TB), who do not have evidence of active TB. Read more about this study
- Who is it for?
- Ages 13 years and older
- Conditions the study is for
- HIV Seropositivity, Tuberculosis, Household Contact
- What is being tested?
- Daily rifapentine and isoniazid for 4 weeks and Weekly rifapentine and isoniazid for 12 weeks
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,000 participants
- Where
- 4 sitesin 4 countries
- Study dates
- 19 Jul 2023to 31 Dec 2025
- Phase
- Phase 4
- 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 13 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Age ≥ 13 years
- Weight > 30 kg
- HIV-seropositive
- HIV viral load <400 copies/mL, defined as "virally suppressed," on an EFV or DTG-based ART regimen (see Section 3.6.2)
- Candidates must meet WHO criteria for receiving TPT
- Age ≥ 13 years
Show all 10Show fewer
- Weight > 30 kg
- HIV-negative
- Household contact of an adult with confirmed rifampicin-sensitive pulmonary TB
- Candidates must meet WHO criteria for receiving TPT
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 recent exposure to a TB case with resistance to isoniazid or rifampicin.
- Previous treatment for active or latent TB for more than 30 days within the past 2 years
- On nevirapine, etravirine, rilpivirine, PI-based, or raltegravir-containing ART regimens
- Known sensitivity or intolerance to isoniazid or rifamycins
Show all 22Show fewer
- Suspected acute hepatitis or known chronic or unstable liver disease^
- ALT > 3 times the upper limit of normal (ULN)
- Total bilirubin > 2.5 times the ULN
- Pregnancy or breastfeeding Females of childbearing potential who are unable or unwilling to use two forms of contraception**
- On prohibited medications (see Appendix I)
- Group 2: HIV-negative household contacts of an adult with confirmed pulmonary TB in Mozambique and Indonesia
- 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 resistance to isoniazid or rifampicin in the source case
- Previous treatment for active or latent TB for >30 days within the past 2 years
- Known sensitivity or intolerance to isoniazid or rifamycins
- Suspected acute hepatitis or known chronic or unstable liver disease^
- ALT > 3 times the upper limit of normal (ULN)
- Total bilirubin > 2.5 times the ULN
- Pregnancy or breastfeeding Females of childbearing potential who are unable or unwilling to use two forms of contraception**
- On prohibited medications
Trial locations and contacts
4 sites in 4 countries.
4 sites in 4 countries
India1 site
The Byramjee Jeejeebhoy Medical Centre (BJGMC-JHU) CRS
Pune, Maharashtra, 411001
Indonesia1 site
Yayasan KNCV - The Persahabatan Hospital, Jakarta
Jakarta, Jaya, 14350
Mozambique1 site
Fundação Aurum (The Aurum Institute Mozambique)
Chokwé, Gaza Province
South Africa1 site
The Aurum Institute: Gavin J Churchyard Legacy Centre
Klerksdorp, North West, 2571
About this study
Official title: A Randomized Trial Comparing Treatment Completion of Daily Rifapentine & Isoniazid for One Month (1HP) To Weekly Rifapentine & Isoniazid For 3 Months (3HP) In Persons Living With HIV and in HIV-negative Household Contacts of Recently Diagnosed Tuberculosis Patients, The "One To Three" Trial
A multicenter, randomized, stratified, open-label, phase IV trial among HIV-positive persons (PLHIV) on antiretroviral therapy (ART), or HIV-negative household contacts of patients with rifampicin-sensitive pulmonary tuberculosis (TB), who do not have evidence of active TB.
Read the detailed description
Participants will be stratified by indication for tuberculosis (TB) preventive treatment (TPT) - HIV seropositive persons or HIV-negative household contact of person with infectious TB - and will receive either one of two TB preventive therapy regimens:
Group 1: People living with HIV infection without active TB
Arm A: isoniazid (300mg) and rifapentine (600mg) daily for 4 weeks (1HP)
Arm B: isoniazid (900mg) and rifapentine (900mg) weekly for 12 weeks (3HP)
Arm A (n=250): 250 participants age ≥13 years of age who are HIV seropositive and taking ART who do not have evidence of active TB will be recruited from local clinics. After being consented, screened, and randomized, participants in Arm A will receive the 1HP regimen once daily for 4 weeks (28 doses).
Study events include a health history, physical exam, TB symptom screen, symptom screen for adverse events (AEs), adherence checks during 1HP, and clinic visits at months 1, 2, and 6, at the least. Safety labs for liver function will be checked as clinically indicated.
Arm B (n=250): 250 participants age ≥13 years of age who are HIV seropositive and taking ART who do not have evidence of active TB will be recruited from local clinics. After being consented, screened, and randomized, participants in Arm B will receive the 3HP regimen once weekly for 12 weeks (12 doses).
Study events include a health history, physical exam, TB symptom screen, symptom screen for adverse events (AEs), adherence checks during 3HP, and clinic visits at months 1, 2, 3, and 6, at the least. Safety labs for liver function will be checked as clinically indicated.
Group 2: HIV-negative household contacts of newly diagnosed adults with rifampicin-sensitive pulmonary TB.
Arm A: isoniazid (300mg) and rifapentine (600mg) daily for 4 weeks (1HP)
Arm B: isoniazid (900mg) and rifapentine (900mg) weekly for 12 weeks (3HP)
Arm A (n=250): 250 participants age ≥13 years of age who are HIV-negative household contacts of adults with rifampicin-sensitive pulmonary TB who do not have evidence of active TB will be recruited from local clinics and households of active cases. After being consented, screened, and randomized, participants in Arm A will receive the 1HP regimen once daily for 4 weeks (28 doses).
Study events include a health history, physical exam, TB symptom screen, symptom screen for adverse events (AEs), adherence checks during 1HP, and clinic visits at months 1, 2, and 6, at the least. Safety labs for liver function will be checked as clinically indicated.
Arm B (n=250): 250 participants age ≥13 years of age who are HIV-negative household contacts of adults with rifampicin-sensitive pulmonary TB who do not have evidence of active TB will be recruited from local clinics and households of active cases. After being consented, screened, and randomized, participants in Arm B will receive the 3HP regimen once weekly for 12 weeks (12 doses).
Study events include a health history, physical exam, TB symptom screen, symptom screen for adverse events (AEs), adherence checks during 3HP, and clinic visits at months 1, 2, 3, and 6, at the least. Safety labs for liver function will be checked as clinically indicated.
- Conditions
- HIV Seropositivity, Tuberculosis, Household Contact
- Being tested
- Daily rifapentine and isoniazid for 4 weeks, Weekly rifapentine and isoniazid for 12 weeks
- Keywords
- Tuberculosis preventive treatment, rifapentine, HIV uninfected
- Medical subject headings
- HIV Seropositivity, Tuberculosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Daily rifapentine and isoniazid for 4 weeksDrug
Arm A: isoniazid (300mg) and rifapentine (600mg) daily for 4 weeks (1HP)
Weekly rifapentine and isoniazid for 12 weeksDrug
Arm B: isoniazid (900mg) and rifapentine (900mg) weekly for 12 weeks (3HP)
| Study group | Role | What they receive |
|---|---|---|
| Group 1: People living with HIV infection without active TB | Experimental | Not described Receives: Drug: Daily rifapentine and isoniazid for 4 weeks; Drug: Weekly rifapentine and isoniazid for 12 weeks |
| Group 2: HIV-negative household contacts of adults with rifampicin-sensitive pulmonary TB | Experimental | Not described Receives: Drug: Daily rifapentine and isoniazid for 4 weeks; Drug: Weekly rifapentine and isoniazid for 12 weeks |
What is being measured
The primary outcome is the main question the study is designed to answer.
Treatment adherence- self-report
Completion of TPT with >90% adherence documented by self-report (both groups, Arms A and B)
Measured: from study entry at Week 0 through up to 8 weeks of 1HP (Group 1) or up to 24 weeks of 3HP (Group 2) , to be reported at end of trial
Treatment adherence- pill count
Completion of TPT with >90% adherence documented by pill count (both groups, Arms A and B)
Measured: from study entry at Week 0 through up to 8 weeks of 1HP (Group 1) or up to 24 weeks of 3HP (Group 2) , to be reported at end of trial
Treatment adherence- electronic monitoring device (EMD)
Completion of TPT with >90% adherence documented by pill count (both groups, Arms A and B)
Measured: from study entry at Week 0 through up to 8 weeks of 1HP (Group 1) or up to 24 weeks of 3HP (Group 2) , to be reported at end of trial
Adverse Events
Occurrence of Grade 2 or higher targeted safety events (both groups, Arms A and B). Targeted safety events are hypersensitivity syndrome, rash, seizure, peripheral neuropathy, hepatotoxicity, nausea and vomiting, and drug-related fever.
Measured: from study entry at Day 0 through Month 6 (Week 24), to be reported at end of trial
Early treatment discontinuation
discontinuation of study medications because of side effects (both groups, Arms A and B)
Measured: from study entry at Week 0 through up to 8 weeks of 1HP (Group 1) or up to 24 weeks of 3HP (Group 2), to be reported at end of trial
Secondary outcomes (1)
Cost-effectiveness
Incremental cost-effectiveness of 1HP and 3HP (compared to each other, ^ months of isoniazid (6H), and no treatment) using a societal perspective.
Measured: from study entry at Week 0 through up to 8 weeks of 1HP (Group 1) or up to 24 weeks of 3HP (Group 2) , to be reported at end of trial
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Nov 2021
- Study start19 Jul 2023
- Primary completion11 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 HIV SeropositivityStudies 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 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- A randomization list will be generated prior to starting enrolment using random block sizes that are stratified by HIV status \& country.
- Masking
- None (open label)
- Enrolment
- 1,000 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
- Gavin Churchyard, Study chair, Aurum Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05118490
- Sponsor's protocol ID
- IRB00298999
- Acronym
- 1 to 3
- Status last verified
- Dec 2025
- First submitted
- 26 Oct 2021
- Last updated
- 12 Dec 2025
- Results posted
- No
- Data monitoring committee
- No
- 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
- A Randomized Trial Comparing Treatment Completion of Daily Rifapentine & Isoniazid for One Month (1HP) To Weekly Rifapentine & Isoniazid For 3 Months (3HP) In Persons Living With HIV and in HIV-negative Household Contacts of Recently Diagnosed Tuberculosis Patients, The "One To Three" Trial
- ClinicalTrials.gov ID
- NCT05118490
- Acronym / sponsor ID
- 1 to 3 / IRB00298999
- Conditions
- HIV Seropositivity, Tuberculosis, Household Contact
- Keywords
- Tuberculosis preventive treatment, rifapentine, HIV uninfected
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 1,000 participants (estimated)
- Lead sponsor
- The Aurum Institute NPCUniversity, hospital or other
- Collaborators
- Johns Hopkins University
- Study start
- 19 Jul 2023 (actual)
- Primary completion
- 11 Jul 2025 (actual)
- Study completion
- 31 Dec 2025 (estimated)
- First posted
- 12 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.
A multicenter, randomized, stratified, open-label, phase IV trial among HIV-positive persons (PLHIV) on antiretroviral therapy (ART), or HIV-negative household contacts of patients with rifampicin-sensitive pulmonary tuberculosis (TB), who do not have evidence of active TB.
Detailed description
Participants will be stratified by indication for tuberculosis (TB) preventive treatment (TPT) - HIV seropositive persons or HIV-negative household contact of person with infectious TB - and will receive either one of two TB preventive therapy regimens:
Group 1: People living with HIV infection without active TB
Arm A: isoniazid (300mg) and rifapentine (600mg) daily for 4 weeks (1HP)
Arm B: isoniazid (900mg) and rifapentine (900mg) weekly for 12 weeks (3HP)
Arm A (n=250): 250 participants age ≥13 years of age who are HIV seropositive and taking ART who do not have evidence of active TB will be recruited from local clinics. After being consented, screened, and randomized, participants in Arm A will receive the 1HP regimen once daily for 4 weeks (28 doses).
Study events include a health history, physical exam, TB symptom screen, symptom screen for adverse events (AEs), adherence checks during 1HP, and clinic visits at months 1, 2, and 6, at the least. Safety labs for liver function will be checked as clinically indicated.
Arm B (n=250): 250 participants age ≥13 years of age who are HIV seropositive and taking ART who do not have evidence of active TB will be recruited from local clinics. After being consented, screened, and randomized, participants in Arm B will receive the 3HP regimen once weekly for 12 weeks (12 doses).
Study events include a health history, physical exam, TB symptom screen, symptom screen for adverse events (AEs), adherence checks during 3HP, and clinic visits at months 1, 2, 3, and 6, at the least. Safety labs for liver function will be checked as clinically indicated.
Group 2: HIV-negative household contacts of newly diagnosed adults with rifampicin-sensitive pulmonary TB.
Arm A: isoniazid (300mg) and rifapentine (600mg) daily for 4 weeks (1HP)
Arm B: isoniazid (900mg) and rifapentine (900mg) weekly for 12 weeks (3HP)
Arm A (n=250): 250 participants age ≥13 years of age who are HIV-negative household contacts of adults with rifampicin-sensitive pulmonary TB who do not have evidence of active TB will be recruited from local clinics and households of active cases. After being consented, screened, and randomized, participants in Arm A will receive the 1HP regimen once daily for 4 weeks (28 doses).
Study events include a health history, physical exam, TB symptom screen, symptom screen for adverse events (AEs), adherence checks during 1HP, and clinic visits at months 1, 2, and 6, at the least. Safety labs for liver function will be checked as clinically indicated.
Arm B (n=250): 250 participants age ≥13 years of age who are HIV-negative household contacts of adults with rifampicin-sensitive pulmonary TB who do not have evidence of active TB will be recruited from local clinics and households of active cases. After being consented, screened, and randomized, participants in Arm B will receive the 3HP regimen once weekly for 12 weeks (12 doses).
Study events include a health history, physical exam, TB symptom screen, symptom screen for adverse events (AEs), adherence checks during 3HP, and clinic visits at months 1, 2, 3, and 6, at the least. Safety labs for liver function will be checked as clinically indicated.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- A randomization list will be generated prior to starting enrolment using random block sizes that are stratified by HIV status \& country.
| Arm | Type | Receives |
|---|---|---|
| Group 1: People living with HIV infection without active TB | Experimental | Drug: Daily rifapentine and isoniazid for 4 weeks, Drug: Weekly rifapentine and isoniazid for 12 weeks |
| Group 2: HIV-negative household contacts of adults with rifampicin-sensitive pulmonary TB | Experimental | Drug: Daily rifapentine and isoniazid for 4 weeks, Drug: Weekly rifapentine and isoniazid for 12 weeks |
Who may qualify
- Ages
- 13 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (10 listed)
- Age ≥ 13 years
- Weight > 30 kg
- HIV-seropositive
- HIV viral load <400 copies/mL, defined as "virally suppressed," on an EFV or DTG-based ART regimen (see Section 3.6.2)
- Candidates must meet WHO criteria for receiving TPT
Key exclusion criteria (22 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 recent exposure to a TB case with resistance to isoniazid or rifampicin.
- Previous treatment for active or latent TB for more than 30 days within the past 2 years
- On nevirapine, etravirine, rilpivirine, PI-based, or raltegravir-containing ART regimens
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 |
|---|---|---|
| Daily rifapentine and isoniazid for 4 weeksArm A: isoniazid (300mg) and rifapentine (600mg) daily for 4 weeks (1HP) | Drug | Group 1: People living with HIV infection without active TB, Group 2: HIV-negative household contacts of adults with rifampicin-sensitive pulmonary TB |
| Weekly rifapentine and isoniazid for 12 weeksArm B: isoniazid (900mg) and rifapentine (900mg) weekly for 12 weeks (3HP) | Drug | Group 1: People living with HIV infection without active TB, Group 2: HIV-negative household contacts of adults with rifampicin-sensitive pulmonary TB |
Primary outcome
Treatment adherence- self-report
Time frame: from study entry at Week 0 through up to 8 weeks of 1HP (Group 1) or up to 24 weeks of 3HP (Group 2) , to be reported at end of trial
Completion of TPT with >90% adherence documented by self-report (both groups, Arms A and B)
Treatment adherence- pill count
Time frame: from study entry at Week 0 through up to 8 weeks of 1HP (Group 1) or up to 24 weeks of 3HP (Group 2) , to be reported at end of trial
Completion of TPT with >90% adherence documented by pill count (both groups, Arms A and B)
Treatment adherence- electronic monitoring device (EMD)
Time frame: from study entry at Week 0 through up to 8 weeks of 1HP (Group 1) or up to 24 weeks of 3HP (Group 2) , to be reported at end of trial
Completion of TPT with >90% adherence documented by pill count (both groups, Arms A and B)
Adverse Events
Time frame: from study entry at Day 0 through Month 6 (Week 24), to be reported at end of trial
Occurrence of Grade 2 or higher targeted safety events (both groups, Arms A and B). Targeted safety events are hypersensitivity syndrome, rash, seizure, peripheral neuropathy, hepatotoxicity, nausea and vomiting, and drug-related fever.
Early treatment discontinuation
Time frame: from study entry at Week 0 through up to 8 weeks of 1HP (Group 1) or up to 24 weeks of 3HP (Group 2), to be reported at end of trial
discontinuation of study medications because of side effects (both groups, Arms A and B)
1 secondary outcome
Cost-effectiveness
Time frame: from study entry at Week 0 through up to 8 weeks of 1HP (Group 1) or up to 24 weeks of 3HP (Group 2) , to be reported at end of trial
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.
Gavin Churchyard study chair
Aurum Institute
4 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Daily rifapentine and isoniazid for 4 weeks and Weekly rifapentine and isoniazid for 12 weeks in people with HIV Seropositivity and Tuberculosis, run by The Aurum Institute NPC at 4 sites in 4 countries.
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 10 inclusion and 22 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 4 sites in India, Indonesia, Mozambique, 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 phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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?
Treatment adherence- self-report (time frame: from study entry at Week 0 through up to 8 weeks of 1HP (Group 1) or up to 24 weeks of 3HP (Group 2) , 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.