Tenofovir Disoproxil
| Evidence Level: L4 | Predicted Indications: 10 |
Table of Contents
- Tenofovir Disoproxil
- Tenofovir Disoproxil: From HIV-1/Hepatitis B Infection to Feline Acquired Immunodeficiency Syndrome
Tenofovir Disoproxil: From HIV-1/Hepatitis B Infection to Feline Acquired Immunodeficiency Syndrome
One-Sentence Summary
Tenofovir disoproxil is a nucleotide reverse transcriptase inhibitor best known as a core component of antiretroviral therapy for HIV-1 infection and as a treatment for chronic hepatitis B virus infection. The TxGNN model predicts it may also be effective against feline acquired immunodeficiency syndrome (the AIDS-like disease caused by Feline Immunodeficiency Virus, FIV, in domestic cats), with 4 clinical trials and 2 publications currently linked to this candidate. However, the linked clinical trials are all human HIV-1 studies rather than feline-specific trials, so the actual disease-specific evidence base is limited to two small preclinical animal studies.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not captured in this Evidence Pack’s EU license data (drug not EU-marketed); publicly known as an HIV-1 and chronic hepatitis B antiviral |
| Predicted New Indication | Feline Acquired Immunodeficiency Syndrome (FIV infection in cats) |
| TxGNN Prediction Score | 99.95% (rank 766) |
| Evidence Level | L4 |
| EU Market Status | ✗ Not marketed |
| Number of Authorizations | 0 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism-of-action data for this candidate is flagged as a data gap in the Evidence Pack (DG002). Based on well-established pharmacological knowledge, tenofovir disoproxil is a prodrug of tenofovir, a nucleotide analogue reverse transcriptase inhibitor (NtRTI). It is administered as part of combination antiretroviral therapy for human HIV-1 infection and is separately approved for chronic hepatitis B virus infection — both indications rely on inhibition of viral reverse transcriptase.
Feline Immunodeficiency Virus (FIV), the cause of feline AIDS, is a lentivirus in the same genus as HIV-1, and it depends on the same reverse-transcriptase-mediated replication mechanism. This shared virology gives the TxGNN prediction a plausible mechanistic basis: a reverse transcriptase inhibitor effective against HIV-1 could, in principle, also suppress FIV replication. This is supported by the Evidence Pack itself — tenofovir already has a validated antiviral track record against HBV (see rank 6, “hepatitis B virus infection”, with dozens of completed Phase 3 trials), reinforcing that the drug’s core mechanism generalizes across unrelated viral families that share reverse-transcriptase or polymerase machinery.
That said, this is a veterinary indication in a non-human species, which falls outside the conventional human drug-repurposing pathway. The mechanistic plausibility does not by itself establish clinical translatability to a regulatory human-indication pipeline, and the specific literature evidence comes from small experimental cat studies rather than controlled clinical trials.
Clinical Trial Evidence
Note: none of the trials below were conducted in cats or for FIV specifically. All four are human HIV-1 antiretroviral trials in which tenofovir disoproxil (as TDF, often within Truvada/Atripla) was used as a comparator or backbone regimen; they were linked to this candidate through the shared “immunodeficiency syndrome” disease ontology term rather than direct feline-disease evidence.
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT01263015 | Phase 3 | Completed | 844 | Dolutegravir + abacavir/lamivudine vs. Atripla (efavirenz/emtricitabine/TDF) over 96 weeks in ART-naive HIV-1 adults |
| NCT01227824 | Phase 3 | Completed | 828 | Dolutegravir vs. raltegravir, each with a dual-NRTI backbone (including TDF/FTC), in ART-naive HIV-1 adults |
| NCT02770508 | Phase 4 | Completed | 145 | Boosted darunavir + lamivudine vs. darunavir + FTC/TDF or 3TC/TDF in ART-naive HIV-1 patients |
| NCT00951015 | Phase 2 | Completed | 208 | Dose-finding for dolutegravir combined with abacavir/lamivudine or tenofovir/emtricitabine in ART-naive HIV-1 adults |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 37112803 | 2023 | Preclinical (animal study) | Viruses | Combination antiretroviral therapy (dolutegravir + tenofovir + emtricitabine) evaluated for pharmacokinetics and immunophenotype in specific-pathogen-free FIV-infected domestic cats |
| 24782459 | 2015 | Preclinical (animal study) | Journal of Feline Medicine and Surgery | Naturally FIV-infected cats treated with an experimental nucleotide analogue (PMEDAP); reports on antiviral effect and tolerability in a small case series |
EU Market Information
Tenofovir disoproxil is not currently authorized for marketing in the EU under the data captured in this Evidence Pack (0 licenses recorded, market status: not marketed). No product-level EU authorization details are available for review.
Safety Considerations
Please refer to the SmPC for safety information.
Conclusion and Next Steps
Decision: Hold
Rationale: The predicted indication is a veterinary disease (feline AIDS/FIV infection), which falls outside the standard human drug-repurposing evaluation scope, and the supporting evidence is limited to two small preclinical animal studies with no controlled clinical trials in the target species or population. While the underlying lentivirus-to-lentivirus mechanistic rationale is biologically plausible, it is not sufficient on its own to support progression given the species mismatch and lack of EU marketing status.
To proceed, the following is needed:
- Confirm whether veterinary indications are in scope for this repurposing pipeline; if not, this candidate should be deprioritized in favor of the model’s human-disease predictions
- Mechanism of action data (DG002) to properly assess cross-species applicability
- TFDA/EMA labeling data on warnings and contraindications (DG001) before any safety pre-assessment (S1) can proceed
- If veterinary development is pursued, dedicated feline pharmacokinetic and controlled efficacy/safety trials, given tenofovir’s known nephrotoxicity risk profile in other species
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.