Lamivudine
| Evidence Level: L4 | Predicted Indications: 10 |
Table of Contents
Lamivudine: From HIV/Hepatitis B to Simian Immunodeficiency Virus Infection
One-Sentence Summary
Lamivudine is a nucleoside reverse transcriptase inhibitor (NRTI) originally used to treat chronic hepatitis B and HIV/AIDS. The TxGNN model predicts it may be effective for simian immunodeficiency virus (SIV) infection, but the support is limited to 15 publications, mostly preclinical (macaque) studies, and no registered clinical trials. This is an animal-model indication that overlaps with the already-approved HIV use, so it does not represent a new human therapeutic indication.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Chronic hepatitis B virus infection; HIV infection / AIDS (the licence records compiled for this report contain no approved indication text) |
| Predicted New Indication | Simian immunodeficiency virus infection |
| TxGNN Prediction Score | 99.93% |
| Evidence Level | L4 |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 10 |
| 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, lamivudine is a nucleoside analogue that inhibits reverse transcriptase, and its efficacy in HIV and hepatitis B is established.
SIV is a lentivirus closely related to HIV and also replicates through reverse transcriptase, so lamivudine activity is mechanistically plausible. Macaque studies of the M184V resistance mutation in SIV reverse transcriptase support this target relationship. The macaque studies also show that the animal model mimics the rapid emergence of lamivudine resistance seen in human HIV-1 therapy.
However, SIV infection is an animal-model disease, not a human therapeutic indication, and it overlaps with the already-approved HIV indication. The prediction is therefore best read as a confirmation of the drug's anti-retroviral mechanism rather than a true repurposing opportunity.
Clinical Trial Evidence
Currently no related clinical trials registered for simian immunodeficiency virus infection.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 12021341 | 2002 | Preclinical (macaque) | J Virol | In newborn macaques treated with lamivudine or emtricitabine, M184V resistance mutants emerged within 5 weeks, mimicking human HIV-1 therapy |
| 12502828 | 2003 | Preclinical (macaque) | J Virol | Tenofovir selects for reversion of the M184V mutation in SIV, even in the presence of lamivudine |
| 15919889 | 2005 | Preclinical (macaque) | J Virol | Efavirenz + lamivudine + tenofovir suppressed viral load in macaques infected with RT-SHIV |
| 16973590 | 2006 | Preclinical (macaque) | J Virol | Rapid viral decay in SIV-infected macaques on quadruple antiretroviral therapy |
| 19240457 | 2009 | Preclinical (macaque) | AIDS | Post-exposure prophylaxis with zidovudine, lamivudine and indinavir was evaluated against vaginal SIV transmission |
| 15040537 | 2004 | In vitro | Antivir Ther | Susceptibility of HIV-2, SIV and SHIV to 16 approved anti-HIV drugs, with implications for treatment and prophylaxis |
| 14610172 | 2003 | Preclinical (macaque) | J Virol | Effect of early short-term HAART on lymphocyte proliferation in SIVmac251 infection |
| 12163615 | 2002 | Preclinical | J Virol | The M184V mutation can delay reversion of attenuated SIV variants |
| 12804006 | 2003 | Preclinical (macaque) | AIDS Res Hum Retroviruses | HAART and infection modulate P-glycoprotein and cellular kinase expression in a primate AIDS model |
| 31658118 | 2020 | Review | Curr Opin HIV AIDS | Islatravir for HIV-1 treatment and prevention (indirect relevance) |
Singapore Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN09134P | EPIVIR TABLET 150 mg | Film-coated tablet | Not specified in the records |
| SIN11152P | ZEFFIX TABLETS 100 mg | Film-coated tablet | Not specified in the records |
| SIN09135P | EPIVIR ORAL SOLUTION 10 mg/ml | Solution | Not specified in the records |
| SIN15204P | LAVUDIN STANDARD F.C. TABLET 100 mg | Film-coated tablet | Not specified in the records |
| SIN15989P | DOVATO FILM-COATED TABLET 50MG/300MG | Film-coated tablet | Not specified in the records |
Ten valid registrations are on record in total. The others include COMBIVIR, ABALAM, Kivexa, DELSTRIGO and TRIUMEQ, which are fixed-dose combinations containing lamivudine.
Safety Considerations
- Contraindication-related conditions from the knowledge graph (not label text): liver failure, liver disease, kidney disease, pancreatitis, neutropenia, agranulocytosis, anaemia, lactic acidosis, myopathy/myositis, hypertriglyceridaemia, fatty liver disease and non-alcoholic steatohepatitis, among others. These should be verified against the package insert.
- Drug interactions: 100 interactions were found. Moderate-level ones include lactitol, mannitol, sorbitol, naltrexone and orlistat. Others, such as metformin, cimetidine, omeprazole, pantoprazole and vancomycin, are of unknown severity.
Please refer to the package insert for authoritative warnings and contraindications.
Conclusion and Next Steps
Decision: Hold
Rationale: The only evidence for SIV infection is preclinical (macaque) work with no registered clinical trials. SIV is an animal-model disease and overlaps with lamivudine's already-approved HIV indication, so it offers no new human therapeutic opportunity.
To proceed, the following is needed:
- A clear decision on whether an animal-model indication has any translational value, since the HIV indication is already covered
- Mechanism of action data from DrugBank
- HSA package insert warnings and contraindications
- Review of the other predicted indications for any more actionable direction
Note on other predictions: Hepatitis B virus infection (rank 6) is an already-approved indication and is not a true repurposing candidate. It has the strongest evidence (L1, with several Phase 3 trials), but lamivudine has a high resistance rate and guidelines favour entecavir or tenofovir. The remaining predictions (chronic hepatitis C, feline AIDS and several rare liver or neurodevelopmental disorders) have no supporting mechanism or only veterinary evidence, and are also rated Hold.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.