Zidovudine
| Evidence Level: L4 | Predicted Indications: 10 |
Table of Contents
Zidovudine: From HIV Infection and AIDS to Feline Acquired Immunodeficiency Syndrome
One-Sentence Summary
Zidovudine (AZT) is a nucleoside reverse transcriptase inhibitor originally used to treat HIV infection and AIDS in humans. The TxGNN model predicts it may be effective for feline acquired immunodeficiency syndrome, a veterinary indication. Support is limited to 19 publications, mostly animal studies, with no registered clinical trials.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | HIV infection, AIDS (taken from the knowledge-graph indication data; the Singapore registration records contain no indication text) |
| Predicted New Indication | Feline acquired immunodeficiency syndrome |
| TxGNN Prediction Score | 99.96% |
| Evidence Level | L4 |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 3 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available in the data compiled for this report. Zidovudine is a nucleoside reverse transcriptase inhibitor, and its efficacy against HIV is well established. Mechanistically, it may be applicable to feline immunodeficiency virus (FIV) as well.
FIV is a lentivirus closely related to HIV-1, and its reverse transcriptase is similar enough that many HIV reverse transcriptase inhibitors also work against it. This is why FIV-infected cats are widely used as an animal model of HIV. Veterinary studies report lower plasma virus levels, reduced provirus burden and better immune function in treated animals.
This is a veterinary indication, not a new human use. The related feline leukaemia virus studies also noted zidovudine toxicity, so the benefit-risk balance in cats is not settled.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
The 10 most relevant of the 19 publications are listed below. None is a randomized controlled trial in humans.
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 22816032 | 2012 | Veterinary clinical study | Viruses | One-year comparison of zidovudine alone and in combination with interferon-α, lamivudine or valproic acid in naturally FIV-infected cats |
| 7495172 | 1995 | Veterinary clinical study | Zentralblatt fur Veterinarmedizin A | Long-term oral AZT (5 mg/kg three times daily) versus symptomatic therapy in diseased FIV-positive field cats |
| 1363008 | 1992 | Veterinary clinical study | Vet Immunol Immunopathol | Efficacy and side effects of AZT and PMEA in naturally infected FIV and FeLV cats with symptoms |
| 25855689 | 2016 | Follow-up study | J Feline Med Surg | Effects of 5–6 years of antiretroviral therapy starting with AZT in FIV-infected cats |
| 7688949 | 1993 | Animal study | Arch Virol | AZT lowered plasma virus titres at 2 weeks but did not prevent infection in experimentally infected cats |
| 8381867 | 1993 | Animal study | J Acquir Immune Defic Syndr | Prophylactic AZT prevented early viremia and lymphocyte decline but not primary infection |
| 7749786 | 1995 | Animal study | J Acquir Immune Defic Syndr Hum Retrovirol | Early suppression of viremia by AZT did not alter the spread of FIV infection; CD4 counts stayed higher in treated cats |
| 7618256 | 1995 | Animal model | Vet Immunol Immunopathol | Reduced provirus burden and enhanced humoral immune function in AZT-treated SCID-feline mice inoculated with FIV |
| 2178336 | 1990 | Animal study (FeLV) | Antimicrob Agents Chemother | Interferon-α plus AZT in presymptomatic FeLV-induced immunodeficiency |
| 2163339 | 1990 | Animal toxicity study (FeLV) | Fundam Appl Toxicol | AZT toxicity in FeLV-infected cats across doses of 7.5–60 mg/kg/day |
Singapore Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN07438P | APO-ZIDOVUDINE CAPSULE 100 mg | Capsule | Not stated in the registration data |
| SIN07527P | RETROVIR ORAL SOLUTION 10 mg/ml | Syrup (oral solution) | Not stated in the registration data |
| SIN10795P | COMBIVIR TABLETS | Film-coated tablet | Not stated in the registration data |
All three registrations are currently valid. They are human medicines, and no veterinary registration appears in the data.
Safety Considerations
- Contraindications suggested by the knowledge graph (disease associations, not package-insert text): liver failure, liver disease, fatty liver disease, non-alcoholic steatohepatitis, kidney disease, pancreatitis, gallbladder disease, myopathy and other muscle diseases (including myositis and dermatomyositis), neutropenia, agranulocytosis, anaemia (including macrocytic anaemia), lactic acidosis, hypertriglyceridemia, obesity disorders, familial periodic paralysis and pyoureter.
- Drug Interactions (100 interactions recorded; 20 reviewed):
- Moderate: amphotericin B (including the cholesteryl sulfate and lipid complex formulations), corticosteroids (betamethasone, budesonide, dexamethasone, hydrocortisone, prednisolone, prednisone, triamcinolone), statins (rosuvastatin, simvastatin), naltrexone and orlistat.
- Minor: cimetidine and clarithromycin.
- Interaction level not classified: pantoprazole, omeprazole, morphine and metformin.
- Animal toxicity: zidovudine toxicity has been reported in FeLV-infected cats.
Please refer to the package insert for warnings and contraindications, which are not available in the data compiled for this report.
Conclusion and Next Steps
Decision: Hold
Rationale: The prediction score is very high, and the mechanistic link through reverse transcriptase inhibition is plausible. However, the evidence is entirely preclinical or veterinary, with no registered trials. The indication is for cats, so it does not extend the human use of a drug already marketed in Singapore, and zidovudine toxicity has been noted in related feline studies.
To proceed, the following is needed:
- Clarification of whether a veterinary indication is within the scope of this repurposing programme
- Controlled veterinary clinical trials with safety and dose data in cats
- Package-insert warnings and contraindications from the Singapore regulator
- Detailed mechanism of action data
- Safety information on haematological toxicity (anaemia, neutropenia) and on liver and kidney function
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.