Tenofovir Alafenamide
| Evidence Level: L4 | Predicted Indications: 3 |
Table of Contents
- Tenofovir Alafenamide
- Tenofovir Alafenamide: From Chronic Hepatitis B to Simian Immunodeficiency Virus Infection
Tenofovir Alafenamide: From Chronic Hepatitis B to Simian Immunodeficiency Virus Infection
One-Sentence Summary
Tenofovir alafenamide (TAF) is a nucleotide reverse transcriptase inhibitor prodrug, with pharmacology data in this evidence pack identifying it as used to treat chronic Hepatitis B virus (HBV) infection. The TxGNN model predicts it may be effective for Simian Immunodeficiency Virus (SIV) Infection, with 1 clinical trial and 9 publications currently supporting this direction — though nearly all of this evidence comes from non-human primate (macaque) research models rather than human disease.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Chronic Hepatitis B virus (HBV) infection (sourced from pharmacology reference data; no official India label text available) |
| Predicted New Indication | Simian Immunodeficiency Virus Infection |
| TxGNN Prediction Score | 99.89% |
| Evidence Level | L4 |
| India Market Status | Not Marketed |
| Number of Registrations | 0 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available. Based on the information present in this evidence pack, tenofovir alafenamide is a nucleotide reverse transcriptase inhibitor (NRTI) prodrug (synonyms: GS-7340, Vemlidy®) whose clinical use is documented as treatment of chronic Hepatitis B virus infection. Its antiviral efficacy relies on inhibiting reverse transcriptase, an enzyme shared across retroviruses and lentiviruses.
Simian Immunodeficiency Virus (SIV) is the non-human-primate analog of HIV and belongs to the same lentivirus family. Because TAF (and its combination with emtricitabine) is an established anti-HIV reverse-transcriptase inhibitor, it is mechanistically plausible that the same enzymatic target confers activity against SIV — which is why nearly all supporting literature consists of macaque SIV/SHIV challenge studies used as translational pre-exposure prophylaxis (PrEP) models for human HIV.
Important caveat: the predicted indication, “simian immunodeficiency virus infection,” is an animal disease used in HIV/PrEP research models, not a standalone human disease target. This prediction should be interpreted as reflecting TAF’s known anti-lentiviral (HIV) research utility rather than a genuinely new human indication, which limits its direct repurposing applicability.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT03577782 | Phase 1/2 | Unknown | 12 | Trial of vedolizumab combined with antiretroviral therapy (ART) in ART-naïve HIV-infected subjects, aiming for virological remission after ART interruption. Trial focuses on human HIV; TAF-specific relevance and SIV relevance are not established in the summary (relevance grading: pending). |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 39632836 | 2024 | Preclinical (macaque model) | Nature Communications | SHIV remission in macaques with early oral emtricitabine/TAF plus long-acting cabotegravir/rilpivirine and immune agent combinations |
| 38134382 | 2024 | Preclinical (macaque model) | J Infect Dis | TAF fumarate/elvitegravir vaginal inserts show extended postexposure protection against vaginal SHIV in macaques |
| 39559349 | 2024 | Preclinical (humanized mouse model) | Frontiers in Immunology | Dual-purpose humanized mouse model developed for testing antiviral strategies against both SIV and HIV |
| 35913838 | 2022 | Preclinical (macaque model) | J Antimicrob Chemother | Biodegradable polycaprolactone implant releasing TAF shows safety/efficacy for vaginal HIV pre-exposure prophylaxis in macaques |
| 31362305 | 2019 | Preclinical (macaque model) | J Infect Dis | Oral TAF/emtricitabine or TAF alone evaluated against vaginal SHIV infection in macaques |
| 31730629 | 2019 | Preclinical (macaque model) | PLoS One | Protocol developed for high-compliance daily oral ARV dosing in rhesus macaques for SIV/SHIV prevention/treatment studies |
| 27465645 | 2016 | Preclinical (macaque model) | J Infect Dis | Oral emtricitabine + TAF chemoprophylaxis protects macaques from rectal SHIV infection |
| 22740713 | 2012 | Preclinical (macaque model) | J Infect Dis | Oral pre-exposure prophylaxis associated with reduced inflammation and CD4 loss in acute SHIV infection |
| 16810108 | 2006 | Preclinical (macaque model) | J Acquir Immune Defic Syndr | Oral tenofovir disoproxil fumarate and topical GS-7340 (TAF) evaluated to protect infant macaques from repeated oral SIV challenge |
India Market Information
Tenofovir alafenamide currently has no registered authorizations in India (0 licenses on record; market status: Not Marketed).
Safety Considerations
- Drug Interactions: The safety pack lists one pharmacology interaction record — a binding association between tenofovir alafenamide and TAS2R39, a bitter-taste receptor. This is an off-target bioactivity/binding assay result, not a clinically actionable drug-drug interaction, and should not be treated as a DDI warning.
No India label warnings, contraindications, or clinically validated drug interaction data are currently available. Please refer to the official package insert for full safety information once available.
Conclusion and Next Steps
Decision: Hold
Rationale: The predicted indication is a non-human-primate disease model (SIV infection in macaques) rather than a validated human disease target, and the single supporting clinical trial does not directly evaluate TAF or SIV. Combined with a Blocking-severity data gap (DG001: missing India label warnings/contraindications, which prevents any initial safety assessment) and missing mechanism-of-action data (DG002), the evidence base is insufficient to advance.
To proceed, the following is needed:
- India label warnings and contraindications (resolves DG001, currently blocking)
- Confirmed mechanism-of-action documentation (resolves DG002)
- Clarification of the actual human-relevant target indication (e.g., HIV PrEP/treatment) that the SIV macaque-model evidence is meant to translate to
- Completion of pending literature classification (study type/tier) and clinical trial relevance grading (NCT03577782)
- A clinically validated drug-drug interaction review, since the current DDI record (TAS2R39) is not clinically actionable
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.