Lamivudine
| Evidence Level: L4 | Predicted Indications: 5 |
Table of Contents
Lamivudine: From Antiviral Therapy to Feline Acquired Immunodeficiency Syndrome
One-Sentence Summary
Lamivudine is a nucleoside reverse transcriptase inhibitor (NRTI) antiviral that is already marketed in South Africa. The TxGNN model predicts it may be effective for feline acquired immunodeficiency syndrome (FIV infection in cats), which is a veterinary disease and not a human indication. Support comes from 5 listed clinical trials, none of which studied FIV (all are human HIV-1 studies), and 5 publications (in vitro, animal and cohort studies in cats).
Quick Overview
| Item | Content |
|---|---|
| Predicted New Indication | Feline acquired immunodeficiency syndrome |
| TxGNN Prediction Score | 99.93% |
| Evidence Level | L4 |
| South Africa Market Status | Marketed |
| Number of SAHPRA Registrations | 20 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available in the Evidence Pack. Lamivudine belongs to the NRTI class, which blocks the reverse transcriptase enzyme that retroviruses use to copy their genetic material. FIV is a lentivirus, in the same family as HIV, and depends on the same enzyme. This makes activity against FIV biologically plausible.
The animal literature supports this link. Studies show that reverse transcriptase inhibitors active against HIV are also active against FIV. This is why the FIV-infected cat is used as an animal model of HIV. Lamivudine (3TC) has been tested against FIV mainly in combination with zidovudine (AZT), with or without abacavir.
This prediction is not a human repurposing candidate. FIV affects cats, and the retrieved human trials show only lamivudine’s established antiretroviral activity, not efficacy in FIV. The Evidence Pack also lists no original indications for lamivudine, so the mapping to its original use is unverified.
Clinical Trial Evidence
All five trials below are human HIV-1 studies. None tests lamivudine in FIV or in cats. Each was graded “C” (low relevance) in the evidence review. They do not count toward the L1 or L2 criteria for this indication. No SANCTR or PACTR registrations were retrieved.
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT01227824 | Phase 3 | Completed | 828 | Dolutegravir vs raltegravir with ABC/3TC or TDF/FTC backbone in ART-naive HIV-1 adults. Lamivudine is background therapy only. |
| NCT02770508 | Phase 4 | Completed | 145 | Boosted darunavir plus lamivudine vs boosted darunavir plus emtricitabine/tenofovir or lamivudine/tenofovir in naive HIV-1 patients. |
| NCT00951015 | Phase 2 | Completed | 208 | Dose selection of dolutegravir with abacavir/lamivudine or tenofovir/emtricitabine in ART-naive HIV-1 adults. |
| NCT01499199 | Phase 3 | Completed | 13 | Single-arm study of dolutegravir plus abacavir/lamivudine, including CNS pharmacokinetics, in HIV-1 adults. |
| NCT01263015 | Phase 3 | Completed | 844 | Dolutegravir plus abacavir/lamivudine vs Atripla in ART-naive HIV-1 adults. |
Literature Evidence
These are the only feline or FIV-specific data. All are in vitro, animal or small cohort studies.
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 22816032 | 2012 | Cohort | Viruses | Compared ZDV alone, ZDV + interferon-α, ZDV + lamivudine and ZDV + valproic acid in naturally FIV-infected cats over one year, using viral load, CD4+/CD8+ ratio and clinical evaluation. |
| 25855689 | 2016 | Cohort | J Feline Med Surg | Follow-up of long-term antiretroviral therapy in FIV-infected cats, started with zidovudine and continued for 5-6 years. |
| 11943320 | 2002 | Animal study | Vet Immunol Immunopathol | AZT/3TC was additive to synergistic against FIV in primary PBMC, but not in chronically infected T-cell lines. Prophylactic and therapeutic efficacy were also evaluated in vivo. |
| 11684314 | 2002 | Animal study | Antiviral Res | Combined ZDV, 3TC and abacavir suppression of FIV replication in vitro, supporting the cat as an HIV model. |
| 11327469 | 2001 | In vitro | Am J Vet Res | Compared replication and nucleoside analog susceptibility of FIV clones, including two 3TC-resistant mutants. |
South Africa Market Information
Lamivudine has 20 SAHPRA registrations. Five are shown below. The approved indication text was not available in the retrieved data. Some products, such as Cipla-duovir and Tenofovir Winthrop, may be combination products, so check each product’s Professional Information (PI).
| Registration Number | Product Name | Dosage Form |
|---|---|---|
| Reg. No. 41/20.2.8/0236 | Adco-lamivudine | Tablet |
| Reg. No. 46/20.2.8/0010 | Lazena | Tablet |
| Reg. No. 45/20.2.8/0108 | Mivuten | Tablet |
| Reg. No. A40/20.2.8/0244 | Cipla-duovir | Tablet |
| Reg. No. 46/20.2.8/0040 | Tenofovir Winthrop | Film-coated tablet (FCT) |
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: The FIV prediction rests on a plausible mechanism and small animal and in vitro studies, and no trial tests lamivudine in FIV. FIV is a veterinary disease, so it is not a human repurposing indication. The lower-ranked predictions in the pack (SIV infection, a rare neurodevelopmental disorder, an obsolete hyperlipidaemia term) have no supporting evidence. The chronic hepatitis C prediction is also not supported: lamivudine has no established activity against HCV, and the retrieved evidence mostly concerns hepatitis B.
To proceed, the following is needed:
- Confirmation of the intended use: veterinary FIV research, or a human indication after re-screening of the prediction list
- Lamivudine’s original indications and mechanism of action, which are missing from the pack
- SAHPRA package insert warnings and contraindications (a blocking gap for safety screening)
- Manual review of NCT06356740 (abacavir/lamivudine in systemic lupus erythematosus, Phase 2, not yet recruiting), the only trial that tests lamivudine directly. It was retrieved under the HCV prediction and is not linked to FIV.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.