Rifabutin
| Evidence Level: L1 | Predicted Indications: 10 |
Table of Contents
Rifabutin: From Tuberculosis/MAC Infection to HIV Infectious Disease
One-Sentence Summary
Rifabutin is a rifamycin-class antimycobacterial, established for treating and preventing tuberculosis (TB) and Mycobacterium avium complex (MAC) infection. The TxGNN model predicts it may be relevant to HIV Infectious Disease, with 39 clinical trials and 20 publications currently supporting this direction — though, as detailed below, this evidence largely reflects rifabutin’s role in managing HIV-associated mycobacterial co-infections rather than a direct antiretroviral effect.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Tuberculosis / Mycobacterium avium complex (MAC) — no UK licence text available in the evidence pack to extract from |
| Predicted New Indication | HIV Infectious Disease |
| TxGNN Prediction Score | 99.88% |
| Evidence Level | L1 |
| UK Market Status | Not marketed |
| Number of Marketing Authorisations | 0 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available for this drug in the evidence pack. Based on known pharmacology, Rifabutin belongs to the rifamycin class of antimycobacterial antibiotics, structurally related to rifampicin, and its efficacy against tuberculosis and MAC infection is well established. Rifabutin was specifically developed as a rifampicin alternative because it is a substantially weaker inducer of cytochrome P450 3A4 (CYP3A4) — a property that makes it far more compatible with antiretroviral regimens (protease inhibitors, NNRTIs, integrase inhibitors) than rifampicin.
The relationship between the original indication and the “new” prediction is not that rifabutin treats HIV itself, but that TB and MAC are the two most significant mycobacterial co-infections in people living with HIV. The overwhelming majority of the supporting trial and literature evidence relates to rifabutin’s use in HIV/TB co-treatment, MAC prophylaxis in advanced HIV/AIDS, and — very heavily — pharmacokinetic drug–drug interaction studies with antiretroviral agents (protease inhibitors, dolutegravir, cabotegravir, maraviroc, etc.), reflecting its critical role as the rifamycin of choice in HIV-positive patients requiring TB or MAC therapy.
Mechanistically, this makes the prediction reasonable as an indication of clinical relevance to the HIV population rather than a genuine antiretroviral repurposing signal. This distinction should be made explicit in any downstream decision material, since “effective for HIV Infectious Disease” could otherwise be misread as anti-HIV activity.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrolment | Key Findings |
|---|---|---|---|---|
| NCT00001030 | Phase 3 | Completed | 1100 | Clarithromycin vs rifabutin vs combination for prevention of MAC bacteraemia/disseminated MAC in advanced HIV |
| NCT00002122 | Phase 3 | Completed | 720 | Azithromycin and rifabutin, alone and combined, for prevention of disseminated MAC in HIV infection |
| NCT00002267 | NA | Completed | 750 | Rifabutin monotherapy vs placebo for prevention of MAC bacteraemia in AIDS patients (CD4 ≤200) |
| NCT00002101 | Phase 3 | Completed | 450 | Clarithromycin/ethambutol with or without rifabutin (2 doses) for treatment of MAC bacteraemia in AIDS |
| NCT00001047 | Phase 3 | Completed | 400 | Four regimens (rifabutin or clofazimine + clarithromycin + ethambutol) for disseminated MAC in AIDS |
| NCT00023361 | NA (TBTC Study 23) | Completed | 215 | Intermittent rifabutin-based regimen for HIV-related, isoniazid/rifamycin-susceptible tuberculosis |
| NCT00023348 | Phase 2/3 | Completed | 150 | Pharmacokinetics of intermittent isoniazid and rifabutin in HIV-related TB (TBTC Study 23A) |
| NCT01663168 | Phase 2 | Unknown | 140 | Toxicity/PK of rifabutin doses with lopinavir/ritonavir second-line ART (EARNEST substudy) |
| NCT00810446 | N/A | Completed | 72 | Post-marketing drug-use surveillance of Mycobutin (rifabutin) in HIV patients (Japan) |
| NCT00651066 | Phase 2 | Completed | 47 | Rifabutin as a rifampicin replacement in combined TB/HIV treatment (Vietnam) |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 23828580 | 2013 | Cochrane Systematic Review | Cochrane Database Syst Rev | Rifamycins (incl. rifabutin) vs isoniazid for TB prevention in HIV-negative people at risk of active TB |
| 21726477 | 2009 | Review | BMJ Clinical Evidence | Evidence review of TB treatment in people with HIV |
| 28233512 | 2017 | Review | Microbiology Spectrum | TB associated with HIV infection — bidirectional disease impact and treatment considerations |
| 7736687 | 1995 | Review | Clinical Pharmacokinetics | Clinical pharmacokinetics of rifabutin; efficacy in MAC prophylaxis in HIV-positive, low-CD4 patients |
| 40310456 | 2025 | Review | PNAS | Next-generation rifamycins for mycobacterial infections; rifamycin–CYP3A4 induction discussion |
| 26832753 | 2016 | Population PK Meta-analysis | J Antimicrob Chemother | Pooled analysis of rifabutin–HIV protease inhibitor drug–drug interactions, dosing implications |
| 25281400 | 2015 | Observational (PK/safety) | J Antimicrob Chemother | PK and safety of rifabutin with lopinavir/ritonavir in young HIV-infected children |
| 31139825 | 2019 | Observational (safety/efficacy) | J Antimicrob Chemother | Safety and efficacy of rifabutin in HIV/TB-coinfected children on lopinavir/ritonavir-based ART |
| 33294914 | 2021 | Observational (PK/safety) | J Antimicrob Chemother | Rifabutin PK and safety in TB/HIV-coinfected children on second-line ART |
| 9459473 | 1998 | Observational Cohort | JAMA | HIV Outpatient Study (HOPS): clarithromycin/rifabutin possibly effective for cryptosporidiosis chemoprophylaxis |
UK Market Information
According to the evidence pack, Rifabutin currently has no recorded UK marketing authorisations (0 licences; market status: Not Marketed). No product name, dosage form, or approved indication text is available to populate a licence table. This should be independently verified against the current MHRA product register before any regulatory conclusions are drawn, as it affects the availability of a UK-approved SmPC for reference.
Safety Considerations
Please refer to the SmPC and BNF for safety information. Report suspected adverse reactions via the Yellow Card Scheme.
(Note: the underlying evidence pack flags the absence of TFDA/MHRA warnings and contraindications as a Blocking data gap — see Conclusion below. Independently of this pack, rifabutin is well known clinically for extensive CYP3A4-mediated interactions with antiretroviral agents, which should be reviewed via the current SmPC once available.)
Conclusion and Next Steps
Decision: Hold
Rationale: The evidence base is strong (L1 — multiple completed Phase 3 trials plus a Cochrane systematic review) and rifabutin’s role in managing HIV-associated TB/MAC co-infection is well documented. However, a Blocking data gap on essential safety information (SmPC warnings/contraindications) prevents entry into the S1 safety review stage, and the drug has no current UK marketing authorisation.
To proceed, the following is needed:
- Resolve DG001: obtain MHRA-approved SmPC/PIL (warnings, contraindications, DDI profile)
- Resolve DG002: source original MOA documentation from DrugBank to strengthen the mechanistic rationale
- Confirm whether any UK access route exists (e.g. named-patient/unlicensed import), given the pack shows zero UK licences
- Reframe the indication precisely as “management of HIV-associated mycobacterial co-infection (TB/MAC)” rather than “HIV Infectious Disease” treatment, to avoid implying direct antiretroviral activity
- Given the extensive documented CYP3A4-mediated interactions with antiretrovirals, commission a full DDI review against the current UK ART formulary before any clinical-use recommendation
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.