Zidovudine
| Evidence Level: L4 | Predicted Indications: 6 |
Table of Contents
Zidovudine: From HIV Infection / AIDS to Simian Immunodeficiency Virus Infection
One-Sentence Summary
Zidovudine is a nucleoside reverse transcriptase inhibitor (NRTI) originally used to treat HIV infection and AIDS. The TxGNN model predicts it may be effective for simian immunodeficiency virus (SIV) infection, but support comes only from animal studies (about 20 publications, 0 clinical trials), so this is a model prediction with preclinical evidence only.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | HIV infectious disease, AIDS (the US licence records contain no indication text) |
| Predicted New Indication | Simian immunodeficiency virus infection |
| TxGNN Prediction Score | 99.96% |
| Evidence Level | L4 |
| US Market Status | Cancelled only (all licences cancelled) |
| Number of NDAs | 13 (3 NDAs and 10 ANDAs) |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available in the data compiled for this report. Based on known information, zidovudine is an NRTI. After phosphorylation inside cells it blocks viral DNA synthesis by reverse transcriptase, and its efficacy in HIV infection is well established.
SIV is a lentivirus closely related to HIV and uses the same reverse transcriptase target. Macaque studies show zidovudine can reduce viral load, protect newborn animals from rapid onset of AIDS, extend survival, and lower central nervous system virus burden. Post-exposure prophylaxis studies in macaques also used zidovudine in combination with other agents.
However, SIV infection is an animal-model counterpart of the drug’s original antiretroviral use, not a new human disease. Several studies also show zidovudine does not prevent infection itself, and a resistant SIV mutant (Q151M) has been described. The prediction is therefore mechanistically plausible but is not a true human repurposing opportunity.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 19240457 | 2009 | Animal study | AIDS | Post-exposure prophylaxis with zidovudine, lamivudine and indinavir after vaginal SIV exposure in macaques |
| 7695293 | 1995 | Animal study | Antimicrob Agents Chemother | Immediate zidovudine protected SIV-infected newborn macaques from rapid onset of AIDS |
| 7797947 | 1995 | Animal study | J Infect Dis | Zidovudine prolonged survival and lowered CNS virus load in perinatally infected rhesus macaques |
| 7690823 | 1993 | Animal study | J Infect Dis | Effect of starting zidovudine 1 to 72 hours after SIV inoculation in rhesus monkeys |
| 7848683 | 1994 | Animal study | AIDS Res Hum Retroviruses | AZT-treated macaques as a model for antilentiviral therapy during acute infection |
| 2016686 | 1991 | Animal study | J Acquir Immune Defic Syndr | Neither FLT nor AZT prevented SIV infection in cynomolgus monkeys; FLT was about 10 times more potent in delaying antigen appearance |
| 9021180 | 1997 | In vitro/virology | Antimicrob Agents Chemother | Zidovudine-resistant SIV mutant (Q151M) caused AIDS in newborn macaques |
| 11020686 | 2000 | Review | Ann Emerg Med | Nonoccupational HIV post-exposure prophylaxis; animal data suggest antiretrovirals reduce SIV transmission |
| 22713337 | 2012 | In vitro/virology | Antimicrob Agents Chemother | Response of SIV to a novel NRTI compared with existing agents |
| 16973590 | 2006 | Animal study | J Virol | Rapid viral decay in SIV-infected macaques on quadruple antiretroviral therapy |
US Market Information
All 13 US licences are cancelled; none are currently valid. The data compiled for this report contain no approved-indication text.
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| NDA019655 | RETROVIR | Capsule | Not available |
| NDA019951 | RETROVIR | Injection, solution | Not available |
| NDA019910 | RETROVIR | Solution | Not available |
| ANDA077267 | Zidovudine | Tablet, film coated | Not available |
| ANDA077558 | Lamivudine and Zidovudine | Tablet, film coated | Not available |
Safety Considerations
- Contraindication-related conditions (from a knowledge graph, not label text): liver failure and liver disease, kidney disease, pancreatitis, gallbladder disease, myopathy and myositis, neutropenia, agranulocytosis, anemia, lactic acidosis, fatty liver disease, hypertriglyceridemia, and obesity-related disorders.
- Drug Interactions: about 100 interactions were recorded. Those listed include moderate interactions with amphotericin B products, corticosteroids (betamethasone, budesonide, dexamethasone, hydrocortisone, prednisolone, prednisone, triamcinolone), naltrexone, rosuvastatin, simvastatin and orlistat, and minor interactions with cimetidine and clarithromycin.
- Animal data: zidovudine toxicity in cats is documented, and hematologic toxicity (anemia, neutropenia) is the best-known concern in humans.
Please refer to the package insert for official warnings and contraindications.
Conclusion and Next Steps
Decision: Hold
Rationale: The prediction score is high, but support is limited to macaque and in vitro studies with no human trials, and the indication is an animal-model version of the drug’s original HIV use. All US licences are also cancelled.
To proceed, the following is needed:
- Clarification of whether SIV infection has any translational purpose beyond serving as a research model
- Detailed mechanism of action data
- Package insert warnings and contraindications for formal safety screening
Other Predicted Indications Reviewed
| Predicted Indication | Evidence Level | Decision | Comment | |——|——|——|——| | Feline acquired immunodeficiency syndrome | L4 | Hold | Veterinary and animal-model evidence only; not a human repurposing candidate | | Neurodevelopmental disorder with ataxic gait, absent speech, and decreased cortical white matter | L5 | Hold | No trials, literature or plausible mechanism; likely a knowledge-graph artifact | | Obsolete familial combined hyperlipidemia | L5 | Hold | Obsolete term with no evidence; NRTIs tend to cause dyslipidemia, not treat it | | Congenital HIV | L1 | Proceed with Guardrails | Phase 3 trials (NCT00102960, NCT00001104) and public health guidance exist, but this is essentially the original HIV indication; monitor for anemia and neutropenia | | AIDS related complex | L1 | Proceed with Guardrails | Phase 3 trial NCT00001011 (n=538) supports use, but ARC is an outdated term and this is the historical original indication; many interactions and hematologic toxicity require guardrails |
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.