Tenofovir Alafenamide
| Evidence Level: L4 | Predicted Indications: 3 |
Table of Contents
- Tenofovir Alafenamide
- Pharmacist Assessment Report
- Tenofovir Alafenamide: From HIV Infection to Simian Immunodeficiency Virus Infection
- One-Sentence Summary
- Quick Overview
- Why is This Prediction Reasonable?
- Clinical Trial Evidence
- Literature Evidence
- Canada Market Information
- Safety Considerations
- Conclusion and Next Steps
- Disclaimer
Tenofovir Alafenamide: From HIV Infection to Simian Immunodeficiency Virus Infection
One-Sentence Summary
Tenofovir alafenamide (TAF) was originally developed to treat HIV infection and AIDS. The TxGNN model predicts it may be effective for simian immunodeficiency virus infection, but this is largely a preclinical model of HIV rather than a truly new human indication. Support currently consists of 0 clinical trials and 8 publications, all preclinical (macaque or humanized mouse studies).
Quick Overview
| Item | Content |
|---|---|
| Original Indication | HIV infection, AIDS |
| Predicted New Indication | Simian immunodeficiency virus infection |
| TxGNN Prediction Score | 0.9989 |
| Evidence Level | L4 |
| Canada Market Status | Marketed (marketed DINs: 7 of 7) |
| Number of DINs | 7 (marketed: 7) |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available from the data compiled for this report. Based on known information, TAF is a prodrug of tenofovir, a nucleotide reverse transcriptase inhibitor. It delivers tenofovir diphosphate efficiently to lymphoid cells after oral dosing.
SIV and SHIV are lentiviruses closely related to HIV-1 and use the same reverse transcriptase-dependent replication cycle, so TAF is expected to be active against them. Macaque studies show protection when TAF is given alone or with emtricitabine as pre- or post-exposure prophylaxis. Delivery formats tested include oral dosing, vaginal implants and topical inserts.
An important caveat: SIV/SHIV infection in macaques is a research model of HIV, and HIV is already an approved indication for TAF. The findings therefore reinforce the existing HIV indication rather than open a new clinical one. Two other predictions have even weaker support. Feline acquired immunodeficiency syndrome is a veterinary indication with no literature. A rare neurodevelopmental disorder has no plausible mechanistic link and is likely a TxGNN model (deep learning) artifact.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 27465645 | 2016 | Preclinical (macaque) | J Infect Dis | Oral emtricitabine + TAF protected macaques from repeated rectal SHIV exposure (PrEP) |
| 31362305 | 2019 | Preclinical (macaque) | J Infect Dis | Oral TAF/FTC and single-agent TAF evaluated against vaginal SHIV infection |
| 35913838 | 2022 | Preclinical (macaque) | J Antimicrob Chemother | Biodegradable TAF implant evaluated for safety and efficacy as vaginal PrEP |
| 38134382 | 2024 | Preclinical (macaque) | J Infect Dis | TAF/elvitegravir vaginal inserts gave extended post-exposure protection against SHIV |
| 39632836 | 2024 | Preclinical (macaque) | Nat Commun | Early oral FTC/TAF plus long-acting cabotegravir/rilpivirine studied for SHIV remission |
| 41342257 | 2026 | Preclinical (macaque) | J Infect Dis | TAF/elvitegravir rectal inserts gave partial post-exposure protection (82.9%) |
| 39559349 | 2024 | Model development | Front Immunol | Humanized mouse model for testing antivirals against both SIV and HIV |
| 31730629 | 2019 | Methods | PLoS One | Protocol for training macaques to take daily oral antiretrovirals |
Canada Market Information
| DIN | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| 02464241 | VEMLIDY | Not specified | Not specified |
| 02454424 | DESCOVY | Not specified | Not specified |
| 02454416 | DESCOVY | Not specified | Not specified |
| 02478579 | BIKTARVY | Not specified | Not specified |
| 02461463 | ODEFSEY | Not specified | Not specified |
Two more authorizations are valid: GENVOYA (02449498) and SYMTUZA (02473720). All 7 are currently valid.
Safety Considerations
- Drug Interactions: The interaction query completed with one pharmacology entry. TAF is listed as a ligand of the bitter taste receptor TAS2R39. This is a target association, not a clinically established drug interaction.
Please refer to the package insert for warnings and contraindications.
Conclusion and Next Steps
Decision: Hold
Rationale: The only supporting evidence is preclinical macaque and mouse work, with no registered clinical trials. SIV/SHIV is a research model of HIV, which is already an approved indication, so this prediction adds little as a new indication. The other two predictions have no supporting evidence.
To proceed, the following is needed:
- Mechanism of action data from DrugBank
- Warnings and contraindications from the Health Canada package insert
- Approved indication text and dosage forms for the Canadian authorizations
- Reframing the question toward a genuinely new human indication, since SIV/SHIV findings only support existing HIV use
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.