Tenofovir Alafenamide
| Evidence Level: L5 | Predicted Indications: 3 |
Table of Contents
- Tenofovir Alafenamide
- Tenofovir Alafenamide: From Antiviral Therapy to Feline Acquired Immunodeficiency Syndrome
Tenofovir Alafenamide: From Antiviral Therapy to Feline Acquired Immunodeficiency Syndrome
One-Sentence Summary
Tenofovir alafenamide (TAF) is an antiviral nucleotide reverse transcriptase inhibitor that is currently marketed in South Africa under 4 SAHPRA registrations. The TxGNN model ranks feline acquired immunodeficiency syndrome as its top prediction, but no clinical trials or publications support it. The best-supported related signal is simian immunodeficiency virus (SIV) infection, with 8 preclinical publications and 1 indirectly related trial.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not stated in the registration data provided |
| Predicted New Indication | Feline acquired immunodeficiency syndrome (veterinary) |
| TxGNN Prediction Score | 99.89% |
| Evidence Level | L5 (SIV infection, rank 2: L4) |
| South Africa Market Status | Marketed |
| Number of SAHPRA Registrations | 4 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not currently available. TAF is a nucleotide reverse transcriptase inhibitor. After it is converted inside cells to tenofovir diphosphate, it blocks the reverse transcriptase enzyme that lentiviruses need to replicate.
Feline immunodeficiency virus (FIV) is a lentivirus that replicates through reverse transcriptase, so an antiviral rationale is plausible. However, this rests only on the model score and class-level reasoning. FIV is also a veterinary pathogen, which limits relevance to human drug repurposing.
The rank 2 prediction, SIV infection, has more support. SIV and SHIV infection in macaques are standard preclinical models of HIV. Several macaque studies test TAF-based regimens directly, including oral emtricitabine/TAF, a vaginal implant and topical GS-7340. This mainly supports the HIV-1 rationale, which is likely already an approved use, so it is probably not a new repurposing signal. The registration data provided contain no original indication, so the HIV-1 label status should be confirmed first.
The rank 3 prediction, a rare genetic neurodevelopmental disorder (ataxic gait, absent speech, decreased cortical white matter), has no identifiable mechanistic link to TAF. Its score (99.87%) is nearly identical to the others, which suggests a knowledge-graph artifact rather than a specific signal.
Clinical Trial Evidence
No clinical trials are currently registered for the rank 1 prediction (feline AIDS). For rank 2 (SIV infection), one trial was retrieved:
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT03577782 | Phase 1/2 | Unknown | 12 | Vedolizumab plus antiretroviral therapy to achieve virological remission in HIV-infected people. The population is HIV, not SIV, and TAF is not the investigational agent, so this is only indirect support (relevance grade C). |
No SANCTR or PACTR records were identified in the data provided.
Literature Evidence
No literature is available for the rank 1 prediction. The table below covers rank 2 (SIV infection). All are animal or model studies, and none is an RCT.
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 39632836 | 2024 | Animal study (macaque) | Nature Communications | Early treatment with oral emtricitabine/TAF and long-acting cabotegravir/rilpivirine in RT-SHIV-infected macaques, aimed at viral remission |
| 38134382 | 2024 | Animal study (macaque) | J Infect Dis | TAF/elvitegravir vaginal inserts for post-exposure protection against SHIV. Earlier work showed 93% and 100% protection when given 4 hours before or after exposure. |
| 39559349 | 2024 | Model development (humanized mouse) | Front Immunol | Dual-purpose mouse model for testing antiviral strategies against both SIV and HIV |
| 35913838 | 2022 | Animal study (macaque) | J Antimicrob Chemother | Safety and efficacy of a biodegradable TAF implant for vaginal PrEP |
| 31362305 | 2019 | Animal study (macaque) | J Infect Dis | Oral TAF/emtricitabine versus TAF alone against repeated vaginal SHIV exposure |
| 31730629 | 2019 | Methods (rhesus macaque) | PLoS One | Protocol for daily oral antiretroviral dosing in macaques with high compliance |
| 27465645 | 2016 | Animal study (macaque) | J Infect Dis | Oral emtricitabine/TAF chemoprophylaxis protected macaques from rectal SHIV infection |
| 22740713 | 2012 | Animal study (macaque) | J Infect Dis | Breakthrough acute SHIV infection during oral PrEP showed reduced inflammation and CD4 loss |
A further study is 16810108 (2006, J Acquir Immune Defic Syndr), which evaluated oral tenofovir disoproxil fumarate and topical tenofovir GS-7340 in infant macaques against repeated oral SIV challenge.
South Africa Market Information
| Registration Number | Product Name | Dosage Form |
|---|---|---|
| Reg. No. 52/20.2.8/0273 | Vemlidy | Fct |
| Reg. No. 55/20.2.8/0080.079 | Tafbin | Fct |
| Reg. No. 55/20.2.8/0455 | Altaeda | Fct |
| Reg. No. 56/20.2.8/0020 | Tavirant | Fct |
The approved indication text and Essential Medicines List status are not available in the data provided.
Safety Considerations
Please refer to the SAHPRA-approved Professional Information (PI) for safety information. Report adverse drug reactions to SAHPRA.
Conclusion and Next Steps
Decision: Hold
Rationale: The top-ranked prediction (feline AIDS) is a veterinary indication with no trials or literature behind it. The SIV signal is preclinical only, and it mostly restates the HIV-1 rationale rather than a new human use. The rank 3 prediction has no plausible mechanistic link.
To proceed, the following is needed:
- SAHPRA package insert data (approved indications, warnings, contraindications), which is required before any safety screening
- Confirmation of the current HIV-1 and hepatitis B label status to judge whether the SIV signal is genuinely new
- Detailed mechanism of action data (for example, from the DrugBank API)
- A clear decision on whether veterinary indications are in scope for human-focused repurposing
This report is for research reference only and does not constitute medical advice. Predicted indications require clinical validation before any application.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.