Lamivudine
| Evidence Level: L4 | Predicted Indications: 5 |
Table of Contents
Lamivudine: Simian immunodeficiency virus infection
One-Sentence Summary
Lamivudine is a nucleoside reverse transcriptase inhibitor, originally used to treat chronic hepatitis B and HIV infection (including AIDS). The TxGNN model predicts it may be effective for simian immunodeficiency virus (SIV) infection, but the supporting evidence is animal-model literature only (15 publications, mostly macaque studies) and no registered clinical trials. This prediction largely restates lamivudine’s existing anti-HIV activity in an animal model and is not a new human indication.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not recorded in the local data |
| Predicted New Indication | Simian immunodeficiency virus infection |
| TxGNN Prediction Score | 0.9993 |
| Evidence Level | L4 |
| Australia Market Status | Listed on the PBS Schedule (1 of 1 items) – TGA (ARTG) registration status is not included in this data |
| Number of PBS Items | 1 (valid: 1) |
| 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 pharmacology, lamivudine is a cytosine nucleoside analogue. Its active triphosphate form inhibits viral reverse transcriptase and terminates the growing DNA chain.
SIV is a lentivirus closely related to HIV and uses a similar reverse transcriptase enzyme. Activity against SIV is therefore biologically plausible. The macaque studies in the literature use lamivudine as part of combination antiretroviral regimens, and they have also studied the M184V resistance mutation that lamivudine selects.
The prediction does not describe a new human use. SIV infects non-human primates, so this is essentially the original HIV indication modelled in animals. It has little bearing on a human repurposing decision.
Other predictions in the top 10 were reviewed and are summarised here for context.
- Feline acquired immunodeficiency syndrome (rank 2): the evidence is veterinary only, with no human trials.
- Hepatitis B virus infection (rank 6): this is already an approved indication, so it validates the model rather than offering a new opportunity. It has the strongest evidence (L1, with multiple completed Phase 3 trials, mostly using lamivudine as a comparator), and it would be the only prediction to reach “Proceed with Guardrails”. Resistance (YMDD mutations) is common with monotherapy, and entecavir or tenofovir are now preferred first-line agents.
- The literature is general hepatitis reviews, and the trials are in HCV/HIV co-infected patients where lamivudine treats the HIV.
- Ranks 3 and 4 (neurodevelopmental disorder, obsolete familial combined hyperlipidaemia): model prediction only, with no trials, no literature and no identifiable mechanistic link.
Clinical Trial Evidence
Currently no related clinical trials registered for simian immunodeficiency virus infection.
Literature Evidence
The evidence below comes from macaque and in vitro studies. No randomised controlled trials in humans were found.
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 19240457 | 2009 | Preclinical (macaque PEP study) | AIDS | Post-exposure prophylaxis with zidovudine, lamivudine and indinavir after vaginal SIV exposure in macaques |
| 15919889 | 2005 | Preclinical (macaque, HAART) | J Virol | Efavirenz, lamivudine and tenofovir suppressed viral load in rhesus macaques infected with RT-SHIV |
| 16973590 | 2006 | Preclinical (macaque) | J Virol | Rapid viral decay in SIV-infected macaques given quadruple antiretroviral therapy |
| 12021341 | 2002 | Preclinical (macaque/in vitro) | J Virol | M184V mutant SIV emerged within 5 weeks of lamivudine or emtricitabine therapy in newborn macaques, with reduced viral fitness |
| 12502828 | 2003 | Preclinical (macaque/in vitro) | J Virol | Tenofovir selected for reversion of M184V in SIV, even in the presence of lamivudine |
| 15040537 | 2004 | In vitro | Antivir Ther | Susceptibility of HIV-2, SIV and SHIV to anti-HIV-1 compounds, with implications for treatment and post-exposure prophylaxis |
| 12163615 | 2002 | In vitro | J Virol | M184V mutation delayed reversion of attenuated SIV variants |
| 12804006 | 2003 | Preclinical (primate) | AIDS Res Hum Retroviruses | HAART (zidovudine, lamivudine, indinavir) altered P-glycoprotein and cellular kinase expression in a primate AIDS model |
| 14610172 | 2003 | Preclinical (macaque) | J Virol | Early post-exposure HAART and lymphocyte proliferation kinetics in SIVmac251 infection (preliminary report) |
| 31658118 | 2020 | Review | Curr Opin HIV AIDS | Islatravir for HIV-1 treatment and prevention (not specific to lamivudine) |
Australia Market Information
| ARTG Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| ARTG 10311Q | 3TC | Tablet 300 mg (oral) | Not recorded in the data compiled for this report |
Safety Considerations
The knowledge graph links lamivudine to the following conditions as contraindication or caution signals. This is graph-derived information and not product label text.
- Liver and biliary: liver failure, liver disease, fatty liver disease, non-alcoholic steatohepatitis, pancreatitis, gallbladder disease
- Renal: kidney disease, pyoureter
- Haematological: neutropenia, agranulocytosis, anaemia (including macrocytic anaemia)
- Muscle: myopathy, muscular disease, skeletal muscle disease, myositis, dermatomyositis, familial periodic paralysis
- Metabolic: lactic acidosis, hypertriglyceridaemia, obesity disorder, monogenic obesity
Drug interactions: 100 interactions were identified in total. The main moderate-level interactions are with:
- Lactitol
- Mannitol
- Sorbitol
- Naltrexone
- Orlistat
Other listed interactions are of unknown severity (for example metformin, omeprazole, pantoprazole, lansoprazole, cimetidine, morphine, vancomycin, amphotericin B and glimepiride).
Please refer to the TGA-approved Product Information (PI) for authoritative warnings and contraindications.
Conclusion and Next Steps
Decision: Hold
Rationale: The SIV prediction is supported only by macaque and in vitro studies, with no human clinical trials. Lamivudine is already approved for HIV, so this is not a genuine new human indication. The evidence level is L4.
To proceed, the following is needed:
- A clear decision on whether the SIV/animal-model prediction has any human relevance. If not, deprioritise it.
- Detailed mechanism of action data
- Approved indication text for the ARTG entry and the TGA Product Information safety content
- If a human repurposing opportunity is wanted, evaluate other predictions on their merits. Hepatitis B is the only one with substantial trial evidence, and it is already an approved use.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.