Emtricitabine
| Evidence Level: L5 | Predicted Indications: 3 |
Table of Contents
Emtricitabine: Feline acquired immunodeficiency syndrome
One-Sentence Summary
Emtricitabine is a nucleoside reverse transcriptase inhibitor, originally used to treat HIV infection and AIDS (always in combination with other antiretrovirals). The TxGNN model predicts it may be effective for simian immunodeficiency virus (SIV) infection, with 0 registered clinical trials and 20 publications (mostly macaque studies) currently supporting this direction. This is an animal-model finding that largely mirrors the existing HIV indication, not a new human use.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not recorded in the local data |
| Predicted New Indication | Feline acquired immunodeficiency syndrome |
| TxGNN Prediction Score | 0.9992 |
| Evidence Level | L5 |
| Australia Market Status | Listed on the PBS Schedule (7 of 7 items) – TGA (ARTG) registration status is not included in this data |
| Number of PBS Items | 7 (valid: 7) |
| Recommended Decision | Hold |
Note: The first-ranked prediction, feline immunodeficiency virus (FIV) infection, is a veterinary indication with a single supporting paper, so this report focuses on the second-ranked prediction, SIV infection, which has the stronger evidence base. A third prediction (a rare neurodevelopmental disorder) has no mechanistic link and no evidence, and is not assessed further.
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available in the data compiled for this report. Based on known pharmacology, emtricitabine is a nucleoside reverse transcriptase inhibitor (NRTI) that acts on HIV-1 reverse transcriptase. Its efficacy in HIV is established, and mechanistically it may be applicable to related lentiviruses that rely on similar reverse transcriptase enzymes.
SIV and SHIV (simian/human immunodeficiency virus) infection in macaques are the standard preclinical models of HIV. Emtricitabine combined with tenofovir (as TDF or TAF) protected macaques from SHIV acquisition in several prophylaxis studies. The emtricitabine resistance pathway (M184V mutation) has also been characterised in SIV. The mechanistic link is therefore well supported.
However, the evidence is entirely animal-model data that serves as a proxy for the already-approved human HIV indication. SIV infection is not a human disease, so this prediction does not represent a genuinely new human indication. The TxGNN score reflects network proximity to HIV rather than independent clinical validation.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
Ten of the 20 publications are listed below, prioritising the most relevant. Study types are based on titles and abstracts as provided.
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 27465645 | 2016 | Preclinical (macaque) | J Infect Dis | Oral emtricitabine + tenofovir alafenamide protected macaques from rectal SHIV infection |
| 31362305 | 2019 | Preclinical (macaque) | J Infect Dis | Oral TAF/emtricitabine or TAF alone tested against vaginal SHIV infection |
| 26743846 | 2016 | Preclinical (macaque) | J Infect Dis | Emtricitabine/TDF prevented vaginal SHIV infection in macaques with Chlamydia and Trichomonas coinfection |
| 23633402 | 2013 | Preclinical (macaque) | J Infect Dis | Emtricitabine/TDF prophylaxis tested against tenofovir-resistant (K65R) SHIV |
| 21632769 | 2011 | Preclinical (macaque) | J Virol | Intermittent Truvada prophylaxis tested against emtricitabine-resistant (M184V) SHIV |
| 12021341 | 2002 | Preclinical (virology) | J Virol | M184V mutant SIV emerged within 5 weeks on lamivudine or emtricitabine in newborn macaques, with reduced viral fitness |
| 22814162 | 2012 | Preclinical (macaque) | Jpn J Infect Dis | Double oral dose of emtricitabine/tenofovir before exposure protected against highly pathogenic SHIV |
| 24914761 | 2014 | Preclinical (macaque) | AIDS Res Hum Retroviruses | HIV vaccine plus partially protective oral PrEP prevented SHIV infection in macaques |
| 22964889 | 2012 | Review | Curr Opin HIV AIDS | Lessons from animal models of antiretroviral prophylaxis |
| 22918448 | 2012 | Review | Curr Opin HIV AIDS | Considerations for antiretroviral chemoprophylaxis in men who have sex with men |
Australia Market Information
Emtricitabine is available in Australia only as fixed-dose combination tablets. No approved indication text was available in the data compiled for this report.
| ARTG Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| ARTG 10347N | Cipla Tenofovir + Emtricitabine 300/200 | Tablet: tenofovir disoproxil fumarate 300 mg with emtricitabine 200 mg | Not available |
| ARTG 11099E | Descovy | Tablet: emtricitabine 200 mg with tenofovir alafenamide 10 mg | Not available |
| ARTG 11649D | Biktarvy | Tablet: bictegravir 50 mg with emtricitabine 200 mg and tenofovir alafenamide 25 mg | Not available |
| ARTG 11732L | Tenofovir Disoproxil Emtricitabine Efavirenz Viatris 300/200/600 | Tablet: tenofovir disoproxil maleate 300 mg with emtricitabine 200 mg and efavirenz 600 mg | Not available |
| ARTG 11104K | Odefsey | Tablet: emtricitabine 200 mg with rilpivirine 25 mg and tenofovir alafenamide 25 mg | Not available |
Two further entries are registered: Genvoya (ARTG 11114Y) and Symtuza (ARTG 11955F). All 7 entries are oral tablets and currently valid.
Safety Considerations
- Contraindications and warnings from the knowledge graph (drug-disease associations from the TxGNN knowledge graph, not label text): liver disease and liver failure, kidney disease, chronic hepatitis B and C virus infection, lactic acidosis, Fanconi renotubular syndrome, hypophosphatemia, osteomalacia and rickets, fatty liver disease and non-alcoholic steatohepatitis, hypertriglyceridemia, long QT syndrome and torsades de pointes, epilepsy, and several psychiatric conditions (anxiety, dysthymic and delusional disorders, paranoid schizophrenia). Many of these likely reflect partner drugs in the combination products rather than emtricitabine alone, and they should be verified against the Product Information.
- Drug Interactions (20 recorded; main ones):
- Major: leflunomide, teriflunomide
- Moderate: cobicistat, methotrexate, interferon beta-1a/1b, peginterferon beta-1a, orlistat, naltrexone, cladribine, clofarabine, epirubicin, idelalisib, tioguanine, trabectedin, cabozantinib, brentuximab vedotin, asparaginase and pegaspargase
- Minor: eribulin
Please refer to the TGA-approved Product Information (PI) for authoritative warnings and contraindications.
Conclusion and Next Steps
Decision: Hold
Rationale: The supporting evidence is entirely preclinical (macaque and virology studies) and is a proxy for the existing HIV indication. SIV infection is not a human disease, so no new human indication is established. The top-ranked feline prediction rests on a single paper whose design could not be verified.
To proceed, the following is needed:
- A clear definition of the intended human use, if any, since the current evidence maps onto the already-approved HIV treatment and prophylaxis indications
- Mechanism of action data (MOA) for emtricitabine
- Approved indication text and Product Information (warnings and contraindications) for the ARTG-listed products
- Full-text review of the literature, since many study designs were inferred from titles and abstracts
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.