Emtricitabine
| Evidence Level: L5 | Predicted Indications: 10 |
Table of Contents
Emtricitabine: From HIV Infection to Simian Immunodeficiency Virus Infection
One-Sentence Summary
Emtricitabine is an antiretroviral drug originally used to treat HIV infection and AIDS. The TxGNN model predicts it may be effective for simian immunodeficiency virus (SIV) infection, with 0 registered clinical trials and 20 publications currently supporting this direction. The evidence is almost entirely from macaque studies, so this is a preclinical extension of the existing HIV indication rather than a new human indication.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | HIV infectious disease; AIDS (the Singapore licence records contain no approved indication text) |
| Predicted New Indication | Simian immunodeficiency virus infection |
| TxGNN Prediction Score | 99.92% |
| Evidence Level | L3 (animal and review literature only; no human trials) |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 5 |
| 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, emtricitabine is a nucleoside reverse transcriptase inhibitor (NRTI). Its efficacy in HIV infection has been established, and it may act in the same way against closely related lentiviruses.
SIV and SHIV (simian/human immunodeficiency virus) are close relatives of HIV-1 and rely on a similar reverse transcriptase. This explains the high TxGNN score. Macaque studies show that emtricitabine combined with tenofovir (TAF or TDF) protects animals from SIV/SHIV acquisition. Examples include rectal and vaginal challenge models and a study of a tenofovir-resistant virus.
The prediction therefore mostly reflects emtricitabine's established anti-HIV activity, seen through an animal model of the same disease. Its clinical relevance is as a translational model for HIV PrEP (pre-exposure prophylaxis) and treatment. It does not point to a new human disease.
Other predictions in the list were also reviewed:
- AIDS related complex and congenital HIV overlap with the approved HIV/AIDS indications, so they are not true repurposing.
- Feline immunodeficiency virus (FIV) has only one veterinary study.
- Predictions such as benign prostate tumours, Brenner tumour and familial combined hyperlipidemia have no mechanistic link and no supporting evidence.
Clinical Trial Evidence
Currently no related clinical trials are registered for the predicted indication (simian immunodeficiency virus infection).
Literature Evidence
The 20 publications are mostly animal studies. The table lists the most relevant ones, with the more direct macaque efficacy studies first.
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 27465645 | 2016 | Animal study | J Infect Dis | Oral emtricitabine + tenofovir alafenamide protected macaques from rectal SHIV infection |
| 31362305 | 2019 | Animal study | J Infect Dis | Oral TAF/emtricitabine or TAF alone tested against vaginal SHIV infection in macaques |
| 26743846 | 2016 | Animal study | J Infect Dis | Emtricitabine/TDF prevented vaginal SHIV infection in macaques coinfected with Chlamydia and Trichomonas |
| 24914761 | 2014 | Animal study | AIDS Res Hum Retroviruses | Polyvalent virus-like particle HIV vaccine combined with partially protective oral PrEP prevented SHIV infection in macaques |
| 39632836 | 2024 | Animal study | Nat Commun | Early oral emtricitabine/TAF plus long-acting cabotegravir/rilpivirine in RT-SHIV-infected macaques, aimed at remission |
| 23633402 | 2013 | Animal study | J Infect Dis | Oral emtricitabine/TDF tested against a tenofovir-resistant (K65R) SHIV in macaques |
| 21632769 | 2011 | Animal study | J Virol | Intermittent Truvada tested against an emtricitabine-resistant (M184V) SHIV |
| 12021341 | 2002 | Preclinical virology | J Virol | M184V mutants emerged within 5 weeks in macaques treated with lamivudine or emtricitabine; the mutant virus showed reduced fitness |
| 22964889 | 2012 | Review | Curr Opin HIV AIDS | Lessons from animal models of antiretroviral prophylaxis for HIV prevention |
| 22918448 | 2012 | Review | Curr Opin HIV AIDS | Considerations on antiretroviral chemoprophylaxis in men who have sex with men |
Singapore Market Information
All five licences are valid single-ingredient registrations in oral film-coated tablet form. The data compiled for this report contain no approved indication text for any of them.
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN14147P | Truvada Tablet 200mg/300mg | Film-coated tablet | Not available in compiled data |
| SIN15322P | Descovy Film Coated Tablet 200 mg/25 mg | Film-coated tablet | Not available in compiled data |
| SIN15321P | Descovy Film Coated Tablet 200 mg/10 mg | Film-coated tablet | Not available in compiled data |
| SIN16015P | Odefsey Film-Coated Tablet 200mg/25mg/25mg | Film-coated tablet | Not available in compiled data |
| SIN15604P | Biktarvy Film-Coated Tablets 50mg/200mg/25mg | Film-coated tablet | Not available in compiled data |
Safety Considerations
Please refer to the package insert for safety information. The package insert warnings and contraindications could not be retrieved for this report.
- Disease-level contraindication signals (knowledge graph, not label text): The TxGNN knowledge graph links emtricitabine to a range of conditions, including:
- Liver and kidney disease: liver failure, liver disease, fatty liver disease, non-alcoholic steatohepatitis, kidney disease, Fanconi renotubular syndrome
- Metabolic and bone conditions: lactic acidosis, hypophosphatemia, osteomalacia, rickets, hypertriglyceridemia, obesity
- Viral hepatitis: chronic hepatitis B and hepatitis C virus infection
- Cardiac rhythm and others: long QT syndrome, torsades de pointes, and some neuropsychiatric conditions
These come from knowledge-graph edges and should be verified against the official label.
- Drug Interactions: 20 interactions were found (DDInter). The two Major interactions are:
- Leflunomide
- Teriflunomide
Most of the others are Moderate, including cobicistat, naltrexone, orlistat, methotrexate, interferon beta-1a/1b, cladribine, clofarabine, epirubicin, idelalisib and cabozantinib. Eribulin is Minor.
Conclusion and Next Steps
Decision: Hold
Rationale:
- The predicted indication is a nonhuman primate model of the already-approved HIV indication. The 20 publications are macaque and review studies, with no registered human trials. This supports translational research but not a new clinical use.
- The package insert safety data are missing, which is a blocking gap for safety screening.
To proceed, the following is needed:
- The HSA package insert (warnings, contraindications and approved indication text) downloaded and parsed
- Mechanism of action data from DrugBank
- A decision on whether this should be treated as a research question about preclinical PrEP models rather than a clinical repurposing candidate
- If a human-relevant direction is wanted, a review of other candidates such as prevention of mother-to-child transmission (PMTCT). The pregnancy pharmacokinetic and safety data for tenofovir/emtricitabine (PMID 23169329, 29406430) are the most clinically relevant evidence found. This overlaps with the existing HIV indication.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.