HIV-infected Participants With Latent TB Infection in High TB Burden CountryPhase 3NCT03785106
Tuberculosis Preventive Therapy Among Latent Tuberculosis Infection in HIV-infected Individuals
A Phase 3 study testing Isoniazid/Rifapentine daily (4 weeks) plus pyridoxine (vitamin B6) and Isoniazid/Rifapentine 12-weekly plus pyridoxine (vitamin B6) in people with HIV-infected Participants With Latent TB Infection in High TB Burden Country, run by The HIV Netherlands Australia Thailand Research Collaboration at 16 sites in Thailand.
Trial summary
The investigators want to know if ultra-short, effective treatment for latent tuberculosis (TB) infection (LTBI) could dramatically reduce the global incidence of active TB or not. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HIV-infected Participants With Latent TB Infection in High TB Burden Country
- What is being tested?
- Isoniazid/Rifapentine daily (4 weeks) plus pyridoxine (vitamin B6) and Isoniazid/Rifapentine 12-weekly plus pyridoxine (vitamin B6)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2,500 participants
- Where
- 16 sitesThailand
- Study dates
- 15 Aug 2019to Mar 2038
- Phase
- Phase 3
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Documented HIV-1 infection by standard HIV test or plasma HIV-1 RNA viral load and received ART within 12 months. Participants received ART more than 12 months would be allowed if CD4 cell counts is less than 350 cells/mm3
- 18 years and older
- Evidence of latent TB infection, either by TST ≥5 mm or positive interferon gamma release assay (IGRA) or history of close contact with active pulmonary TB* within 3 months prior entry visit or residing in a high TB burden area** NOTE * close contact is referred to person living/sharing in the same room with active pulmonary TB participants for > 4 hours/day
- high TB burden areas are defined as areas with an estimated or reported TB prevalence of 100 to 300/100,000, according to the WHO. Thailand is included in high TB burden areas.
- Laboratory values obtained within 30 days prior to entry
- Absolute neutrophil count (ANC) >750 cells/mm3
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- Hemoglobin >7.4 g/dL
- Platelet count >50,000/mm3
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) <3x upper limit of normal (ULN)
- Total bilirubin <2.5 X ULN
- Chest radiograph or chest computed tomography (CT) scan without evidence of active tuberculosis, unless one has been performed within 90 days prior to entry.
- Female participants who are participating in sexual activity that could lead to pregnancy must agree to use one reliable non-hormonal form of contraceptive (i.e., condoms, IUD, diaphragm) during RPT treatment and contraception should be remain to 6 weeks post RPT NOTE Female participants who are not of reproductive potential or whose male partner(s) have undergone successful vasectomy with documented azoospermia or have documented azoospermia are eligible without requiring the use of contraceptives. Participant-reported history is acceptable documentation of menopause, hysterectomy, or bilateral oophorectomy or bilateral tubal ligation.
- All participants must agree not to participate in a conception process (e.g., active attempt to become pregnant or to impregnate, donate sperm, in vitro fertilization) while receiving RPT and for 6 weeks after stopping this drug.
- Body weight > 40 kg
- Ability and willingness of participant to provide informed consent
Who cannot join
- Treatment for active or latent TB (pulmonary or extrapulmonary) within 2 years prior to study entry or presence of any confirmed or probable active TB at screening.
- History of Isoniazid (INH) or Rifampicin (RIF)/Rifabutin (RFB) resistant TB at any time prior to study entry or known exposure to INH or RIF/RFB resistant TB (e.g., household member of a person with MDR or XDR TB) at any time prior to study entry.
- Treatment for >14 consecutive days with a rifamycin or >30 consecutive days with INH at any time during the 2 years prior to enrollment.
- Current or planned use of protease inhibitor-based ART.
- Currently on a salvage ART regimen, defined as a regimen started due to confirmed HIV virologic failure on a prior ART regimen or due to known HIV drug resistance.
- History of liver cirrhosis at any time prior to study entry.
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- Evidence of acute hepatitis, such as abdominal pain, jaundice, dark urine, and/or light stools within 90 days prior to entry.
- Diagnosis of porphyria at any time prior to study entry.
- Peripheral neuropathy ≥Grade 2 according to the Division of AIDS (DAIDS) Toxicity Table, within 90 days prior to study entry.
- Known allergy/sensitivity or any hypersensitivity to components of study drug(s) or their formulation.
- Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements.
- Acute or serious illness requiring systemic treatment and/or hospitalization within 30 days prior to entry.
- Pregnancy or breastfeeding
Trial locations and contacts
16 sites in 1 country.
16 sites in 1 country
Thailand16 sites
Klang Hospital
Bangkok, 10100
Bhumibol Adulyadej Hospital
Bangkok, 10220
HIV-NAT, Thai Red Cross AIDS Research Centre
Bangkok, 10330
King Chulalongkorn Memorial Hospital
Bangkok, 10330
Police General Hospital
Bangkok, 10330
Taksin Hospital
Bangkok, 10600
the Public Health Centre 28 Krung thon buri
Bangkok, 10600
Sanpatong Hospital
Chiang Mai, 50120
Chiangrai Prachanukroh Hospital
Chiang Rai, 57000
Queen Savang Vadhana Memorial Hospital
Chon Buri, 20110
Srinagarind Hospital
Khon Kaen, 40002
Maharat Nakhon Ratchasima Hospital
Nakhon Ratchasima, 30000
Pranangklao Hospital
Nonthaburi, Changwat Nonthaburi, 11000
Buddhachinnaraj Hospital
Phitsanulok, 65000
Sisaket Hospital
Si Sa Ket, 33000
Hatyai Hospital
Songkhla, 90110
About this study
Official title: Implementation for Tuberculosis Preventive Therapy Among Latent Tuberculosis Infection in HIV-infected Individuals Using Novel Regimen of Isoniazid/Rifapentine Daily (4 Weeks) Compared to Isoniazid/Rifapentine Weekly (12 Weeks)
The investigators want to know if ultra-short, effective treatment for latent tuberculosis (TB) infection (LTBI) could dramatically reduce the global incidence of active TB or not. The investigators hypothesize that short-course (4-week) daily isoniazid/rifapentine (INH/RPT) (1HP) is not inferior to standard -course (12 weeks) INH/RPT weekly regimen (3HP) for the prevention of TB in human immunodeficiency virus (HIV)-infected individuals.
Read the detailed description
This study is a multicenter, randomized, open-label, phase III clinical trial comparing a 4-week daily INH/RPT regimen (1HP) to a 12-weekly INH/RPT (3HP) for the treatment of LTBI in HIV-infected participants without evidence of active TB. The primary objective will be efficacy of active TB prevention. The study will also assess safety and tolerability of the regimens, adherence to the treatments, and patterns of antibiotic resistance among Mycobacterium tuberculosis (MTB) isolates in participants who fail on these prophylactic regimens.
Under this study, there is one substudy entitled, "Pharmacokinetic study of rifapentine, dolutegravir, and tenofovir alafenamide in HIV-infected individual with latent tubersulosis infection". There will be a subgroup of patients who will participate in this pharmacokinetic study of rifapentine and dolutegravir (DTG) / tenofovir alafenamide (TAF). Randomization is based on cluster of differentiation 4 (CD4) categories : < 200, 200-350, > 500 cells/mm3 and VL <50 or >50 copies/ml.
- Being tested
- Isoniazid/Rifapentine daily (4 weeks) plus pyridoxine (vitamin B6), Isoniazid/Rifapentine 12-weekly plus pyridoxine (vitamin B6)
- Keywords
- people living with HIV (PLHIV)
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Isoniazid/Rifapentine daily (4 weeks) plus pyridoxine (vitamin B6)Drug
Isoniazid/Rifapentine daily (4 weeks) plus pyridoxine (vitamin B6)
Isoniazid/Rifapentine 12-weekly plus pyridoxine (vitamin B6)Drug
Isoniazid/Rifapentine 12-weekly plus pyridoxine (vitamin B6)
| Study group | Role | What they receive |
|---|---|---|
| 1HP | Experimental | 4-week daily regimen of weight-based RPT and INH, plus pyridoxine (vitamin B6) Receives: Drug: Isoniazid/Rifapentine daily (4 weeks) plus pyridoxine (vitamin B6) |
| 3HP | Active comparator | 12-weekly INH/RPT regimen, plus pyridoxine (vitamin B6) Receives: Drug: Isoniazid/Rifapentine 12-weekly plus pyridoxine (vitamin B6) |
What is being measured
The primary outcome is the main question the study is designed to answer.
efficacy in preventing active TB (proportion of participants that do not have active TB by the end of the study)
proportion of participants that do not have active TB by the end of the study
Measured: 3 years
safety of the regimens (proportion of participants that do not have any side effects throughout the study period)
proportion of participants that do not have any side effects throughout the study period
Measured: 3 years
tolerability to the regimens (proportion of participants that can complete the treatment course)
proportion of participants that can complete the treatment course
Measured: 3 years
prevalence of drug resistance of MTB
proportion of participants with drug resistance to MTB
Measured: 3 years
Secondary outcomes (19)
severity of the condition
proportion of participants that have side effects of grade more than or equal to 3 signs
Measured: 3 years
presence of symptoms
proportion of participants that have symptoms during the study period
Measured: 3 years
level of CBC
assess the level of CBC
Measured: 3 years
level of ALT
assess the level of ALT
Measured: 3 years
level of AST
assess the level of AST
Measured: 3 years
level of total bilirubin
assess the level of total bilirubin
Measured: 3 years
level of ALK
assess the level of ALK
Measured: 3 years
level of creatinine
assess the level of creatinine
Measured: 3 years
death
time from randomization to death from any cause (TB and non TB events)
Measured: 3 years
when TB culture becomes positive
how much time does it take to have positive TB culture
Measured: 3 years
when TB is confirmed by clinical examination
how much time does it take to have TB diagnosed via clinical examination
Measured: 3 years
adherence to LTBI treatment
proportion of pills missed during treatment period based on self report
Measured: 3 years
consistency of taking LTBI treatment
proportion of pills missed during treatment period based on clinical assessment
Measured: 3 years
treatment discontinuation
proportion of participants with permanent LTBI treatment discontinuation due to all causes
Measured: 3 years
discontinuation of study due to adverse drug reactions
Proportion of participants that have discontinued the study because of adverse drug reactions
Measured: 3 years
CD4 count
CD4 count at baseline
Measured: 3 years
CD4 count to confirmed or probable TB
CD4 count at time from randomization to culture-confirmed or probable TB
Measured: 3 years
time it takes for TB to be confirmed by IGRA
how much time does it take to confirm TB diagnosis via IGRA
Measured: 3 years
TST result at baseline
TST result at day 0
Measured: day 0
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Dec 2018
- Study start15 Aug 2019
- Primary completionMar 2038 (estimated)
- Study completionMar 2038 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HIV-infected Participants With Latent TB Infection in High TB Burden CountryStudies 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 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- This study is a multicenter, randomized, open-label, phase III clinical trial comparing a 4-week daily INH/RPT regimen (1HP) to a 12-weekly INH/RPT (3HP) for the treatment of LTBI in HIV-infected participants without evidence of active TB.
- Masking
- None (open label)
- Enrolment
- 2,500 participants (actual)
Sponsor and investigators
- Lead sponsor
- The HIV Netherlands Australia Thailand Research Collaboration
- Sponsor type
- University, hospital or other
- Collaborators
- King Chulalongkorn Memorial Hospital, Police General Hospital, Pranangklao Hospital, Taksin Hospital, Bhumibol Adulyadej Hospital, Klang Hospital, Chiangrai Prachanukroh Hospital, Sanpatong Hospital, Queen Sawang Vadhana Memorial Hospital, Buddhachinaraj Hospital, Maharat Nakhon Ratchasima Hospital, HatYai Hospital, Srinagarind Hospital, Khon Kaen University, Sisaket Hospital, The Public Health Centre 28 Krung thon buri
- Responsible party
- Sponsor
- Investigators
- Anchalee Avihingsanon, MD, PhD, Principal investigator, Thai Red Cross AIDS Research Centre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03785106
- Sponsor's protocol ID
- HIV-NAT 255
- Status last verified
- Sep 2026
- First submitted
- 19 Dec 2018
- Last updated
- 16 Sep 2026
- 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 16 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Implementation for Tuberculosis Preventive Therapy Among Latent Tuberculosis Infection in HIV-infected Individuals Using Novel Regimen of Isoniazid/Rifapentine Daily (4 Weeks) Compared to Isoniazid/Rifapentine Weekly (12 Weeks)
- ClinicalTrials.gov ID
- NCT03785106
- Acronym / sponsor ID
- HIV-NAT 255
- Keywords
- people living with HIV (PLHIV)
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 2,500 participants (actual)
- Lead sponsor
- The HIV Netherlands Australia Thailand Research CollaborationUniversity, hospital or other
- Collaborators
- King Chulalongkorn Memorial Hospital, Police General Hospital, Pranangklao Hospital, Taksin Hospital, Bhumibol Adulyadej Hospital, Klang Hospital, Chiangrai Prachanukroh Hospital, Sanpatong Hospital, Queen Sawang Vadhana Memorial Hospital, Buddhachinaraj Hospital, Maharat Nakhon Ratchasima Hospital, HatYai Hospital, Srinagarind Hospital, Khon Kaen University, Sisaket Hospital, The Public Health Centre 28 Krung thon buri
- Study start
- 15 Aug 2019 (actual)
- Primary completion
- Mar 2038 (estimated)
- Study completion
- Mar 2038 (estimated)
- First posted
- 24 Dec 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.
The investigators want to know if ultra-short, effective treatment for latent tuberculosis (TB) infection (LTBI) could dramatically reduce the global incidence of active TB or not. The investigators hypothesize that short-course (4-week) daily isoniazid/rifapentine (INH/RPT) (1HP) is not inferior to standard -course (12 weeks) INH/RPT weekly regimen (3HP) for the prevention of TB in human immunodeficiency virus (HIV)-infected individuals.
Detailed description
This study is a multicenter, randomized, open-label, phase III clinical trial comparing a 4-week daily INH/RPT regimen (1HP) to a 12-weekly INH/RPT (3HP) for the treatment of LTBI in HIV-infected participants without evidence of active TB. The primary objective will be efficacy of active TB prevention. The study will also assess safety and tolerability of the regimens, adherence to the treatments, and patterns of antibiotic resistance among Mycobacterium tuberculosis (MTB) isolates in participants who fail on these prophylactic regimens.
Under this study, there is one substudy entitled, "Pharmacokinetic study of rifapentine, dolutegravir, and tenofovir alafenamide in HIV-infected individual with latent tubersulosis infection". There will be a subgroup of patients who will participate in this pharmacokinetic study of rifapentine and dolutegravir (DTG) / tenofovir alafenamide (TAF). Randomization is based on cluster of differentiation 4 (CD4) categories : < 200, 200-350, > 500 cells/mm3 and VL <50 or >50 copies/ml.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- This study is a multicenter, randomized, open-label, phase III clinical trial comparing a 4-week daily INH/RPT regimen (1HP) to a 12-weekly INH/RPT (3HP) for the treatment of LTBI in HIV-infected participants without evidence of active TB.
| Arm | Type | Receives |
|---|---|---|
| 1HP | Experimental | Drug: Isoniazid/Rifapentine daily (4 weeks) plus pyridoxine (vitamin B6)4-week daily regimen of weight-based RPT and INH, plus pyridoxine (vitamin B6) |
| 3HP | Active comparator | Drug: Isoniazid/Rifapentine 12-weekly plus pyridoxine (vitamin B6)12-weekly INH/RPT regimen, plus pyridoxine (vitamin B6) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Documented HIV-1 infection by standard HIV test or plasma HIV-1 RNA viral load and received ART within 12 months. Participants received ART more than 12 months would be allowed if CD4 cell counts is less than 350 cells/mm3
- 18 years and older
- Evidence of latent TB infection, either by TST ≥5 mm or positive interferon gamma release assay (IGRA) or history of close contact with active pulmonary TB* within 3 months prior entry visit or residing in a high TB burden area** NOTE * close contact is referred to person living/sharing in the same room with active pulmonary TB participants for > 4 hours/day
- high TB burden areas are defined as areas with an estimated or reported TB prevalence of 100 to 300/100,000, according to the WHO. Thailand is included in high TB burden areas.
- Laboratory values obtained within 30 days prior to entry
Key exclusion criteria (13 listed)
- Treatment for active or latent TB (pulmonary or extrapulmonary) within 2 years prior to study entry or presence of any confirmed or probable active TB at screening.
- History of Isoniazid (INH) or Rifampicin (RIF)/Rifabutin (RFB) resistant TB at any time prior to study entry or known exposure to INH or RIF/RFB resistant TB (e.g., household member of a person with MDR or XDR TB) at any time prior to study entry.
- Treatment for >14 consecutive days with a rifamycin or >30 consecutive days with INH at any time during the 2 years prior to enrollment.
- Current or planned use of protease inhibitor-based ART.
- Currently on a salvage ART regimen, defined as a regimen started due to confirmed HIV virologic failure on a prior ART regimen or due to known HIV drug resistance.
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 |
|---|---|---|
| Isoniazid/Rifapentine daily (4 weeks) plus pyridoxine (vitamin B6)Isoniazid/Rifapentine daily (4 weeks) plus pyridoxine (vitamin B6) | Drug | 1HP |
| Isoniazid/Rifapentine 12-weekly plus pyridoxine (vitamin B6)Isoniazid/Rifapentine 12-weekly plus pyridoxine (vitamin B6) | Drug | 3HP |
Primary outcome
efficacy in preventing active TB (proportion of participants that do not have active TB by the end of the study)
Time frame: 3 years
proportion of participants that do not have active TB by the end of the study
safety of the regimens (proportion of participants that do not have any side effects throughout the study period)
Time frame: 3 years
proportion of participants that do not have any side effects throughout the study period
tolerability to the regimens (proportion of participants that can complete the treatment course)
Time frame: 3 years
proportion of participants that can complete the treatment course
prevalence of drug resistance of MTB
Time frame: 3 years
proportion of participants with drug resistance to MTB
19 secondary outcomes
severity of the condition
Time frame: 3 years
presence of symptoms
Time frame: 3 years
level of CBC
Time frame: 3 years
level of ALT
Time frame: 3 years
level of AST
Time frame: 3 years
level of total bilirubin
Time frame: 3 years
level of ALK
Time frame: 3 years
level of creatinine
Time frame: 3 years
death
Time frame: 3 years
when TB culture becomes positive
Time frame: 3 years
when TB is confirmed by clinical examination
Time frame: 3 years
adherence to LTBI treatment
Time frame: 3 years
consistency of taking LTBI treatment
Time frame: 3 years
treatment discontinuation
Time frame: 3 years
discontinuation of study due to adverse drug reactions
Time frame: 3 years
CD4 count
Time frame: 3 years
CD4 count to confirmed or probable TB
Time frame: 3 years
time it takes for TB to be confirmed by IGRA
Time frame: 3 years
TST result at baseline
Time frame: day 0
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 16 Sep 2026.
- Individual participant dataSharing planned: No
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.
Anchalee Avihingsanon, MD, PhD principal investigator
Thai Red Cross AIDS Research Centre
16 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Isoniazid/Rifapentine daily (4 weeks) plus pyridoxine (vitamin B6) and Isoniazid/Rifapentine 12-weekly plus pyridoxine (vitamin B6) in people with HIV-infected Participants With Latent TB Infection in High TB Burden Country, run by The HIV Netherlands Australia Thailand Research Collaboration at 16 sites in Thailand.
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 15 inclusion and 13 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 16 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 16 sites in Thailand. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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?
efficacy in preventing active TB (proportion of participants that do not have active TB by the end of the study) (time frame: 3 years). 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?
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 16 Sep 2026.