Rifabutin
| Evidence Level: L5 | Predicted Indications: 10 |
Table of Contents
Rifabutin: HIV infectious disease
One-Sentence Summary
Rifabutin is a rifamycin antibacterial. The approved indication text is not recorded in the local data. The TxGNN model predicts it may be relevant to HIV infectious disease. The 30+ registered trials and 20 publications retrieved were mostly about treating or preventing mycobacterial infections in people with HIV, or about drug interactions with antiretrovirals. None of them treats HIV infection itself, so the evidence level is L5.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not recorded in the local data |
| Predicted New Indication | HIV infectious disease |
| TxGNN Prediction Score | 0.9988 |
| Evidence Level | L5 |
| Australia Market Status | Listed on the PBS Schedule (1 of 1 items) – TGA (ARTG) registration status is not included in this data |
| Number of PBS Items | 1 (valid: 1) |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism of action data are not available in the data compiled for this report. Rifabutin is a rifamycin that inhibits bacterial DNA-dependent RNA polymerase (rpoB). It has no direct activity against HIV.
The link to HIV is indirect. People with advanced HIV are prone to opportunistic mycobacterial infections, namely Mycobacterium avium complex (MAC) and tuberculosis. Rifabutin has been studied for preventing and treating these infections. It is a weaker CYP3A inducer than rifampicin, so it is often preferred when a patient also takes protease inhibitors. It still interacts significantly with several antiretrovirals (for example dolutegravir, lopinavir/ritonavir and long-acting cabotegravir/rilpivirine), and these interactions need dose adjustment and monitoring.
The prediction is best read as “HIV-associated MAC/TB management”, not as treatment of HIV infection. No cited study evaluates rifabutin for HIV infection itself, which is why the evidence level is L5.
Clinical Trial Evidence
These trials enrolled people with HIV, but they address mycobacterial disease, pharmacokinetics or drug interactions. None addresses HIV infection as the treated condition.
| Trial Number | Phase | Status | Enrolment | Key Findings |
|---|---|---|---|---|
| NCT00002101 | Phase 3 | Completed | 450 | Clarithromycin/ethambutol with rifabutin (two doses) or placebo for MAC bacteraemia in AIDS |
| NCT00001047 | Phase 3 | Completed | 400 | Four regimens for disseminated MAC in AIDS, including clarithromycin plus ethambutol with rifabutin or clofazimine |
| NCT00001030 | Phase 3 | Completed | 1100 | Clarithromycin vs rifabutin vs both for preventing MAC bacteraemia in HIV patients with CD4 ≤100 |
| NCT00002122 | Phase 3 | Completed | 720 | Azithromycin and rifabutin, alone and combined, for preventing disseminated MAC in HIV; fluconazole dosing also compared |
| NCT00002267 | Not specified | Completed | 750 | Double-blind, placebo-controlled rifabutin monotherapy for preventing MAC bacteraemia in AIDS |
| NCT00001995 | Not specified | Completed | 200 | Double-blind randomised trial of a rifabutin-containing regimen for MAC bacteraemia in AIDS |
| NCT00023361 | Not specified | Completed | 215 | Intermittent rifabutin-based regimen for HIV-related tuberculosis (TBTC Study 23) |
| NCT00651066 | Phase 2 | Completed | 47 | Rifabutin pharmacokinetics with antiretroviral therapy in TB/HIV co-infection (Vietnam) |
| NCT00640887 | Phase 2 | Completed | 48 | Rifabutin pharmacokinetics with antiretroviral therapy in TB/HIV co-infection (South Africa) |
| NCT00810446 | Not specified | Completed | 72 | Post-marketing drug-use investigation of Mycobutin in HIV patients (real-world safety) |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 33294914 | 2021 | Cohort | J Antimicrob Chemother | Rifabutin pharmacokinetics and safety in TB/HIV-coinfected children on lopinavir/ritonavir; an earlier paediatric study was stopped early for severe neutropenia |
| 31139825 | 2019 | Cohort | J Antimicrob Chemother | Safety and efficacy of rifabutin in HIV/TB-coinfected children on lopinavir/ritonavir-based ART |
| 21819645 | 2012 | Review | Int J Tuberc Lung Dis | Rifabutin as an alternative to rifampicin with protease inhibitor-based ART |
| 17181373 | 2006 | Review | Drugs | Practical therapeutic approach to TB/HIV co-infection |
| 28233512 | 2017 | Review | Microbiol Spectrum | Overview of TB associated with HIV infection |
| 21726477 | 2009 | Review | BMJ Clin Evid | Treating tuberculosis in people with HIV |
| 21418688 | 2010 | Review | BMJ Clin Evid | Primary and secondary prophylaxis of opportunistic infections in HIV |
| 36385424 | 2023 | Pharmacokinetic modelling | Br J Clin Pharmacol | Population PK model of the rifabutin–dolutegravir interaction |
| 36377436 | 2023 | Modelling study | Clin Infect Dis | Managing interactions between long-acting cabotegravir/rilpivirine and inducers such as rifabutin |
| 11996607 | 2002 | Review | Arch Intern Med | Update on rifampin and rifabutin drug interactions |
Australia Market Information
| ARTG Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| 6195C | Mycobutin | Capsule 150 mg (oral) | Not stated in the data compiled for this report |
Safety Considerations
- Drug Interactions: 100 interacting drugs were identified. Examples:
- Major: eliglustat.
- Moderate: clarithromycin, doxycycline, metronidazole, pioglitazone, saxagliptin, linagliptin, aprepitant, morphine, and corticosteroids (hydrocortisone, dexamethasone, betamethasone, triamcinolone).
- Minor: dolasetron.
- Haematological risk: severe neutropenia led to early termination of one paediatric study of rifabutin with protease inhibitors, and treatment-limiting neutropenia occurred in children in a related study (see the literature table). Monitoring of blood counts is advisable.
- Antiretroviral interactions: the trials and publications above describe significant interactions with several antiretrovirals, requiring dose adjustment and monitoring.
Please refer to the TGA-approved Product Information (PI) for full warnings and contraindications.
Conclusion and Next Steps
Decision: Hold
Rationale: No cited study treats HIV infection itself. The trials and publications concern mycobacterial disease (MAC and TB) in people with HIV, or drug interactions with antiretrovirals, so the evidence level is L5. Rifabutin has no antiviral mechanism.
To proceed, the following is needed:
- A clear definition of the intended indication (for example HIV-associated MAC/TB prophylaxis or treatment rather than HIV infection itself), supported by studies that directly address it
- Mechanism of action data and the TGA PI warnings and contraindications
- A drug-interaction management plan for common antiretroviral regimens
- A haematological monitoring plan, particularly for children and patients on protease inhibitors
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.