Tenofovir Alafenamide

Evidence Level: L4 Predicted Indications: 3

Table of Contents

  1. Tenofovir Alafenamide
    1. Pharmacist Assessment Report
    2. Tenofovir Alafenamide: From HIV Infection to Simian Immunodeficiency Virus Infection
    3. One-Sentence Summary
    4. Quick Overview
    5. Why is This Prediction Reasonable?
    6. Clinical Trial Evidence
    7. Literature Evidence
    8. Australia Market Information
    9. Safety Considerations
    10. Conclusion and Next Steps
    11. Disclaimer

Pharmacist Assessment Report

Tenofovir Alafenamide: From HIV Infection to Simian Immunodeficiency Virus Infection

One-Sentence Summary

Tenofovir alafenamide (TAF) is an antiretroviral originally used to treat HIV infection and AIDS. The TxGNN model predicts it may be effective for simian immunodeficiency virus (SIV) infection, with no registered clinical trials and 8 preclinical publications (mainly macaque studies) currently supporting this direction. SIV infection is an animal research model rather than a human disease, so this prediction mostly reflects a translational proxy for the already-approved HIV indication.

Quick Overview

Item Content
Original Indication HIV infectious disease; AIDS
Predicted New Indication Simian immunodeficiency virus infection
TxGNN Prediction Score 0.9989
Evidence Level L4
Australia Market Status Listed on the PBS Schedule (5 of 5 items) – TGA (ARTG) registration status is not included in this data
Number of PBS Items 5 (valid: 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 pharmacology, TAF is a prodrug of tenofovir and a nucleotide reverse transcriptase inhibitor active against HIV-1 and HIV-2. It delivers tenofovir diphosphate efficiently into lymphoid cells after oral administration.

SIV and the chimeric SHIV are closely related lentiviruses that use the same reverse transcriptase target as HIV. The antiviral mechanism is therefore directly applicable, and the high TxGNN score is consistent with this similarity to the original HIV indication.

However, SIV infection is a veterinary and preclinical research model, not a human disease. The macaque studies are best read as supporting evidence for HIV prevention and treatment, not as a new human therapeutic indication. The other predictions in the list (feline AIDS, and a rare neurodevelopmental disorder) have no supporting studies. The neurodevelopmental prediction has no plausible mechanistic link and is likely a TxGNN model (deep learning) artefact.

Clinical Trial Evidence

Currently no related clinical trials registered.

Literature Evidence

All eight publications are preclinical. No RCTs or human studies were identified.

PMID Year Type Journal Key Findings
27465645 2016 Preclinical (macaque) J Infect Dis Oral emtricitabine/TAF used as PrEP in macaques exposed rectally to SHIV
31362305 2019 Preclinical (macaque) J Infect Dis Oral TAF/emtricitabine or TAF alone tested against repeated vaginal SHIV exposure
35913838 2022 Preclinical (macaque) J Antimicrob Chemother Biodegradable TAF-releasing 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 (earlier work: 93% protection before and 100% after exposure)
39632836 2024 Preclinical (macaque) Nat Commun Oral emtricitabine/TAF plus long-acting cabotegravir/rilpivirine, with or without an immune agent, tested for SHIV remission
41342257 2026 Preclinical (macaque) J Infect Dis Rectal TAF/elvitegravir inserts gave partial post-exposure protection (82.9%)
39559349 2024 Preclinical (humanised mouse) Front Immunol Dual-purpose humanised mouse model for testing antivirals against SIV and HIV
31730629 2019 Methods/model development PLoS One Protocol for training macaques to take daily oral ARVs for preclinical studies

Australia Market Information

All five ARTG entries are fixed-dose combination tablets containing TAF. Approved indication text was not available in the data compiled for this report.

ARTG Number Product Name Dosage Form Approved Indication
ARTG 11099E Descovy Tablet: emtricitabine 200 mg / tenofovir alafenamide 10 mg Not available
ARTG 11649D Biktarvy Tablet: bictegravir 50 mg / emtricitabine 200 mg / tenofovir alafenamide 25 mg Not available
ARTG 11104K Odefsey Tablet: emtricitabine 200 mg / rilpivirine 25 mg / tenofovir alafenamide 25 mg Not available
ARTG 11114Y Genvoya Tablet: tenofovir alafenamide 10 mg / emtricitabine 200 mg / elvitegravir 150 mg / cobicistat 150 mg Not available
ARTG 11955F Symtuza Tablet: darunavir 800 mg / cobicistat 150 mg / emtricitabine 200 mg / tenofovir alafenamide 10 mg Not available

Safety Considerations

Please refer to the TGA-approved Product Information (PI) for safety information.

The only interaction-related entry in the data compiled for this report is a pharmacology record linking TAF to the taste receptor TAS2R39. It is not a clinically meaningful drug interaction.

Conclusion and Next Steps

Decision: Hold

Rationale: The only supporting evidence is preclinical (macaque and humanised mouse models), and SIV infection is not a human disease. It offers no new human therapeutic indication beyond the already-approved HIV indication. The other predicted indications have no supporting evidence.

To proceed, the following is needed:

  • Reframing the question toward a human indication, such as HIV pre-exposure prophylaxis, if that is not already covered by current approvals
  • Approved indication text and safety information (warnings, contraindications) from the TGA Product Information for each ARTG entry
  • Detailed mechanism of action data
  • A review of whether any of the macaque PrEP or PEP findings have human trial counterparts

    Disclaimer

This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.

This site uses Just the Docs, a documentation theme for Jekyll.