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 (1 to 3)

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Tuberculosis; HIV Seropositivity; Household Contact
• Intervention / Treatment: Drug: Daily rifapentine and isoniazid for 4 weeks; Drug: Weekly rifapentine and isoniazid for 12 weeks

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 Type: Interventional
• Enrollment (Estimated): 1000
• Phase: Phase 4

Contacts and Locations

Study Locations

• India
  • Maharashtra
    • Pune, Maharashtra, India, 411001
      • The Byramjee Jeejeebhoy Medical Centre (BJGMC-JHU) CRS
• Indonesia
  • Jaya
    • Jakarta, Jaya, Indonesia, 14350
      • Yayasan KNCV - The Persahabatan Hospital, Jakarta
• Mozambique
  • Gaza Province
    • Chokwé, Gaza Province, Mozambique
      • Fundação Aurum (The Aurum Institute Mozambique)
• South Africa
  • North West
    • Klerksdorp, North West, South Africa, 2571
      • The Aurum Institute: Gavin J Churchyard Legacy Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 13 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Group 1: HIV-positive adolescents and adults in South Africa and India

Inclusion criteria:

1. Age ≥ 13 years
2. Weight > 30 kg
3. HIV-seropositive
4. HIV viral load <400 copies/mL, defined as "virally suppressed," on an EFV or DTG-based ART regimen (see Section 3.6.2)
5. Candidates must meet WHO criteria for receiving TPT

Exclusion criteria:

1. 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)
2. Likely to move from the study area during the study period
3. Known recent exposure to a TB case with resistance to isoniazid or rifampicin.
4. Previous treatment for active or latent TB for more than 30 days within the past 2 years
5. On nevirapine, etravirine, rilpivirine, PI-based, or raltegravir-containing ART regimens
6. Known sensitivity or intolerance to isoniazid or rifamycins
7. Suspected acute hepatitis or known chronic or unstable liver disease^
8. ALT > 3 times the upper limit of normal (ULN)
9. Total bilirubin > 2.5 times the ULN
10. Pregnancy or breastfeeding Females of childbearing potential who are unable or unwilling to use two forms of contraception**
11. On prohibited medications (see Appendix I)

Group 2: HIV-negative household contacts of an adult with confirmed pulmonary TB in Mozambique and Indonesia

Inclusion criteria:

1. Age ≥ 13 years
2. Weight > 30 kg
3. HIV-negative
4. Household contact of an adult with confirmed rifampicin-sensitive pulmonary TB
5. Candidates must meet WHO criteria for receiving TPT

Exclusion criteria:

1. 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)
2. Likely to move from the study area during the study period
3. Known exposure to TB cases with resistance to isoniazid or rifampicin in the source case
4. Previous treatment for active or latent TB for >30 days within the past 2 years
5. Known sensitivity or intolerance to isoniazid or rifamycins
6. Suspected acute hepatitis or known chronic or unstable liver disease^
7. ALT > 3 times the upper limit of normal (ULN)
8. Total bilirubin > 2.5 times the ULN
9. Pregnancy or breastfeeding Females of childbearing potential who are unable or unwilling to use two forms of contraception**
10. On prohibited medications

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1: People living with HIV infection without active TB	Drug: Daily rifapentine and isoniazid for 4 weeks; Arm A: isoniazid (300mg) and rifapentine (600mg) daily for 4 weeks (1HP); Drug: Weekly rifapentine and isoniazid for 12 weeks; Arm B: isoniazid (900mg) and rifapentine (900mg) weekly for 12 weeks (3HP)
Experimental: Group 2: HIV-negative household contacts of adults with rifampicin-sensitive pulmonary TB	Drug: Daily rifapentine and isoniazid for 4 weeks; Arm A: isoniazid (300mg) and rifapentine (600mg) daily for 4 weeks (1HP); Drug: Weekly rifapentine and isoniazid for 12 weeks; Arm B: isoniazid (900mg) and rifapentine (900mg) weekly for 12 weeks (3HP)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment adherence- self-report	Completion of TPT with >90% adherence documented by self-report (both groups, Arms A and B)	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)	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)	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.	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)	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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cost-effectiveness	Incremental cost-effectiveness of 1HP and 3HP (compared to each other, ^ months of isoniazid (6H), and no treatment) using a societal perspective.	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

Collaborators and Investigators

• Sponsor: The Aurum Institute NPC
• Collaborators: Johns Hopkins University
• Investigators: Study Chair: Gavin Churchyard, Aurum Institute

Study record dates

Study Major Dates

• Study Start (Actual): July 19, 2023
• Primary Completion (Actual): July 11, 2025
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: October 26, 2021
• First Submitted That Met QC Criteria: November 11, 2021
• First Posted (Actual): November 12, 2021

Study Record Updates

• Last Update Posted (Estimated): December 12, 2025
• Last Update Submitted That Met QC Criteria: December 5, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: rifapentine; Tuberculosis preventive treatment; HIV uninfected
• Additional Relevant MeSH Terms: Blood-Borne Infections; Urogenital Diseases; Genital Diseases; Immune System Diseases; Infections; RNA Virus Infections; Virus Diseases; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Actinomycetales Infections; Mycobacterium Infections; HIV Infections; Tuberculosis; HIV Seropositivity; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Hydrazines; Isonicotinic Acids; Acids, Heterocyclic; Isoniazid
• Other Study ID Numbers: IRB00298999

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No