Rifabutin
| Evidence Level: L5 | Predicted Indications: 10 |
Table of Contents
Rifabutin: HIV infectious disease
One-Sentence Summary
Rifabutin is a rifamycin-class antimycobacterial agent. The TxGNN model predicts it may be relevant to HIV infectious disease (score 0.9988). The data compiled for this report include 35 clinical trials and 20 publications, but none tests rifabutin as a treatment for HIV infection itself, so the evidence level is L5. The studies concern mycobacterial infections in people with HIV, or drug interactions with antiretrovirals.
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 |
| Canada Market Status | Marketed (marketed DINs: 1 of 1) |
| Number of DINs | 1 (marketed: 1) |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism of action data are not currently available in the data compiled for this report. Rifabutin belongs to the rifamycin class of antibacterials. Rifamycins as a class inhibit bacterial RNA polymerase, and rifabutin is also a CYP3A4 inducer and substrate.
Rifabutin is not an antiretroviral and has no known antiviral mechanism. Its link to HIV comes from its use in HIV-associated opportunistic infections, such as disseminated Mycobacterium avium complex (MAC) disease and tuberculosis co-infection. It is often considered in place of rifampicin because it has a weaker enzyme-inducing effect on many antiretrovirals. The trials and publications reflect this: they study mycobacterial disease or drug interactions in people with HIV, not HIV infection as the target of treatment.
The high model score is therefore best read as reflecting how often rifabutin appears alongside HIV in the research literature. It is not evidence that rifabutin treats HIV.
Clinical Trial Evidence
35 trials were identified. None treats HIV infection itself. The ten most relevant are shown below.
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT00001047 | Phase 3 | Completed | 400 | Four regimens for disseminated MAC in AIDS: clarithromycin at two doses plus ethambutol and either rifabutin or clofazimine |
| NCT00002101 | Phase 3 | Completed | 450 | Clarithromycin/ethambutol with rifabutin (two doses) or placebo for MAC bacteremia in AIDS |
| NCT00001995 | N/A | Completed | 200 | Double-blind trial of a rifabutin-containing regimen for MAC bacteremia in AIDS |
| NCT00001030 | Phase 3 | Completed | 1100 | Clarithromycin vs rifabutin vs both for preventing MAC disease in HIV-infected patients with CD4 ≤100 |
| NCT00002122 | Phase 3 | Completed | 720 | Azithromycin and rifabutin, alone and combined, for preventing disseminated MAC in HIV infection |
| NCT00001058 | Phase 2 | Completed | 246 | Clarithromycin combined with rifabutin, ethambutol, or both for disseminated MAC in AIDS |
| NCT00001023 | N/A | Completed | 91 | Safety, tolerance and pharmacokinetics of rifabutin with clarithromycin or azithromycin in HIV-infected patients |
| NCT00651066 | Phase 2 | Completed | 47 | Rifabutin pharmacokinetics with antiretroviral therapy in HIV-associated tuberculosis (Vietnam) |
| NCT00640887 | Phase 2 | Completed | 48 | Rifabutin pharmacokinetics with antiretroviral therapy in HIV-associated tuberculosis (South Africa) |
| NCT00000877 | Phase 1 | Completed | 31 | Steady-state interaction of indinavir and rifabutin given together vs staggered |
Literature Evidence
No randomized trials were found among the publications. The ten most relevant are shown below.
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 33294914 | 2021 | Cohort | J Antimicrob Chemother | Rifabutin pharmacokinetics and safety in children with TB/HIV on lopinavir/ritonavir-based ART; an earlier study in children stopped early because of severe neutropenia |
| 31139825 | 2019 | Cohort | J Antimicrob Chemother | Safety and efficacy of rifabutin in HIV/TB-coinfected children on lopinavir/ritonavir ART; treatment-limiting neutropenia reported previously |
| 28233512 | 2017 | Review | Microbiol Spectr | Interplay of tuberculosis and HIV infection |
| 17181373 | 2006 | Review | Drugs | Practical approach to treating TB/HIV co-infection, including drug interaction constraints |
| 8785257 | 1996 | Review | Clin Infect Dis | Rifabutin in pulmonary TB, including HIV-infected patients |
| 36385424 | 2023 | PK modeling | Br J Clin Pharmacol | Population pharmacokinetic model of the rifabutin–dolutegravir interaction |
| 36377436 | 2023 | Modeling study | Clin Infect Dis | Modeling of interactions between long-acting cabotegravir/rilpivirine and inducers such as rifabutin |
| 39037240 | 2024 | Population PK | Antimicrob Agents Chemother | Rifabutin dosing in HIV/TB co-infected children on lopinavir/ritonavir |
| 21819645 | 2012 | Not classified | Int J Tuberc Lung Dis | Whether rifabutin can replace rifampicin alongside protease-inhibitor ART |
| 10456381 | 1999 | Not classified | Drug Safety | Risk-benefit assessment of therapies for MAC infection, including rifabutin |
Canada Market Information
| DIN | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| 02063786 | MYCOBUTIN | Not specified | Not specified |
One valid single-ingredient licence is on record. The approved indication text is not recorded in the local data.
Safety Considerations
- Drug Interactions: The interaction query returned 100 records. Of the 20 shown in detail, one is rated Major (eliglustat), one Minor (dolasetron), and the remainder Moderate. The Moderate group includes clarithromycin, metronidazole, doxycycline, several corticosteroids (dexamethasone, hydrocortisone, betamethasone, triamcinolone), morphine, aprepitant, and several antidiabetic agents (pioglitazone, saxagliptin, linagliptin, chlorpropamide, acetohexamide).
- Antiretroviral interactions: The trials and publications show that rifabutin interacts with protease inhibitors, non-nucleoside reverse transcriptase inhibitors, integrase inhibitors, and long-acting agents. Dose adjustment and pharmacokinetic monitoring are usually needed.
- Haematological toxicity: Published paediatric cohorts report neutropenia, including treatment-limiting cases, when rifabutin is given with protease-inhibitor-based ART.
Please refer to the package insert for the full warnings and contraindications.
Conclusion and Next Steps
Decision: Hold
Rationale: No trial or publication studies rifabutin as a treatment for HIV infection itself. The existing evidence covers mycobacterial disease in people with HIV and antiretroviral drug interactions. Rifabutin has no known antiviral mechanism, so the prediction is not supported at the evidence level required to proceed (L5).
To proceed, the following is needed:
- Mechanistic or preclinical evidence of anti-HIV activity, or a clearly stated clinical question, such as HIV-associated mycobacterial disease, that matches the existing evidence
- Mechanism of action data
- Package insert warnings and contraindications for Canada
- A drug interaction and haematological monitoring plan for use with antiretroviral regimens
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.