Zidovudine
| Evidence Level: L4 | Predicted Indications: 6 |
Table of Contents
Zidovudine: From HIV Infection to Simian Immunodeficiency Virus Infection
One-Sentence Summary
Zidovudine is a nucleoside reverse transcriptase inhibitor (NRTI) used in antiretroviral therapy, and its South African registrations are mainly HIV products. The TxGNN model predicts it may be effective for simian immunodeficiency virus (SIV) infection, but this is an animal-model disease with no human patients. The supporting evidence is 0 clinical trials and 20 publications, all preclinical (mostly macaque studies), so this prediction is not a human repurposing candidate.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | HIV infection (inferred from the antiretroviral products registered; the registration records contain no indication text) |
| Predicted New Indication | Simian immunodeficiency virus infection |
| TxGNN Prediction Score | 99.96% |
| Evidence Level | L4 |
| South Africa Market Status | Marketed |
| Number of SAHPRA Registrations | 9 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available in the Evidence Pack. Zidovudine is a well-known NRTI. Inside cells it is converted to its triphosphate form, which blocks reverse transcriptase and terminates the growing viral DNA chain.
SIV is a lentivirus closely related to HIV, and its reverse transcriptase is similar to that of HIV-1. A drug that blocks HIV replication is therefore expected to block SIV too, which explains the high model score. The macaque literature confirms this: zidovudine reduced viral load, prolonged survival and, in some newborn animals, prevented infection.
The limits matter. SIV infects non-human primates only, so this indication has no human patient population. The literature validates the mechanism and serves as a preclinical model for HIV drug development. It does not support a human repurposing claim.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
The pack contains 20 publications, and the 10 most relevant are listed below. All are animal or in vitro studies. No RCTs or human studies were found.
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 1489181 | 1992 | Animal study | Antimicrob Agents Chemother | Oral AZT prevented SIV infection in infant rhesus macaques |
| 19240457 | 2009 | Animal study | AIDS | Post-exposure prophylaxis with zidovudine, lamivudine and indinavir against vaginal SIV transmission in macaques |
| 7848683 | 1994 | Animal study | AIDS Res Hum Retroviruses | Effect of AZT on viral load during acute SIV infection in cynomolgus macaques |
| 7695293 | 1995 | Animal study | Antimicrob Agents Chemother | Immediate AZT protected SIV-infected newborn macaques against rapid onset of AIDS |
| 7797947 | 1995 | Animal study | J Infect Dis | AZT prolonged survival and lowered CNS viral load in perinatally infected macaques, but did not prevent infection |
| 7690823 | 1993 | Animal study | J Infect Dis | Effects of starting zidovudine 1 to 72 hours after SIV inoculation in rhesus monkeys |
| 2016686 | 1991 | Animal study | J Acquir Immune Defic Syndr | Antiviral effects of 3’-fluorothymidine versus zidovudine in SIV-infected cynomolgus monkeys; neither prevented infection |
| 9021180 | 1997 | Virology / animal | Antimicrob Agents Chemother | A zidovudine-resistant SIV mutant (Q151M) caused AIDS in newborn macaques |
| 8452370 | 1993 | In vitro | Antimicrob Agents Chemother | AZT versus neutralising antibodies against SIV infection in macaque macrophages |
| 16973590 | 2006 | Animal study | J Virol | Rapid viral decay in SIV-infected macaques on quadruple antiretroviral therapy |
South Africa Market Information
| Registration Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| Reg. No. 44/20.2.8/0106 | Adco lamivudine & zidovudine 150mg/300mg | Tablet | Not stated in records |
| Reg. No. 32/20.2.8/0200 | Retrovir/3tc HIV starter pack (AZT) 100m | Kit | Not stated in records |
| Reg. No. 43/20.2.8/0363 | Hevaz | Tablet | Not stated in records |
| Reg. No. A40/20.2.8/0244 | Cipla-duovir | Tablet | Not stated in records |
| Reg. No. 36/7.5/0372 | Simayla Simvastatin 40 | Tablet | Not stated in records |
Nine registrations exist in total, and five are shown. Simayla Simvastatin 40 is a statin product, so its link to zidovudine looks like a data-matching error. It should be checked against the SAHPRA register.
Safety Considerations
Please refer to the SAHPRA-approved Professional Information (PI) for safety information. Report adverse drug reactions to SAHPRA.
Conclusion and Next Steps
Decision: Hold
Rationale: SIV infection occurs only in non-human primates, so the 20 macaque publications support the mechanism but not a human indication. There are no clinical trials, and the evidence stays at L4. The Evidence Pack lists the missing SAHPRA package insert safety data as a blocking gap.
Two other predictions in the pack have human relevance:
- Congenital HIV (L3, Proceed with Guardrails): this is an established use for preventing mother-to-child transmission and neonatal prophylaxis, not a new repurposing.
- AIDS-related complex (L1, Proceed with Guardrails): this is a historical term for symptomatic HIV disease, and zidovudine is long-established therapy for it. Both are better handled as separate on-label reviews.
To proceed, the following is needed:
- Download and parse the SAHPRA package insert to obtain warnings and contraindications (blocking gap).
- Mechanism of action data from DrugBank.
- Confirmation of the original indication, since the registration records contain no indication text.
- Correction or confirmation of the Simayla Simvastatin 40 registration link.
- A decision to re-scope the review to a human-relevant indication, such as congenital HIV or AIDS-related complex. If so, guardrails would include monitoring for anaemia and neutropenia, weight- and age-based neonatal dosing, and regimen selection per current guidelines.
This report is for research reference only and does not constitute medical advice. Repurposing candidates require clinical validation before use.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.