Tenofovir Disoproxil
| Evidence Level: L5 | Predicted Indications: 10 |
Table of Contents
- Tenofovir Disoproxil
- Tenofovir Disoproxil: From HIV/AIDS and Chronic Hepatitis B to Simian Immunodeficiency Virus Infection
Tenofovir Disoproxil: From HIV/AIDS and Chronic Hepatitis B to Simian Immunodeficiency Virus Infection
One-Sentence Summary
Tenofovir disoproxil is an antiviral originally used to treat chronic hepatitis B and HIV infection/AIDS. The TxGNN model predicts it may be effective for simian immunodeficiency virus (SIV) infection, an infection of non-human primates. This direction currently has 0 clinical trials and 20 publications, nearly all of them animal studies or reviews. SIV is an animal disease model, not a human indication, and it overlaps with the already approved HIV use.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Chronic hepatitis B virus infection; HIV infection / AIDS (the Singapore licence records contain no indication text) |
| Predicted New Indication | Simian immunodeficiency virus infection |
| TxGNN Prediction Score | 99.95% |
| Evidence Level | L4 (preclinical studies only) |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 7 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available in the data compiled for this report. Tenofovir disoproxil is the oral prodrug of tenofovir, a nucleotide reverse transcriptase inhibitor. Based on known pharmacology, tenofovir diphosphate is incorporated into viral DNA and terminates chain elongation. Its efficacy in HIV-1 and hepatitis B is established.
SIV is the monkey counterpart of HIV-1. Both are lentiviruses with similar reverse transcriptases, so activity in macaque models is biologically consistent. The literature shows tenofovir-based regimens being used in macaques for pre-exposure prophylaxis and for long-term antiretroviral therapy.
Two limitations apply. SIV infection is a research model rather than a human disease, so the finding does not create a new treatable human condition. The evidence also confirms what is already known for HIV, so it is not a true repurposing opportunity.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
All entries below are animal studies or reviews. No human randomised trial is linked to this predicted indication.
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 16960777 | 2006 | Preclinical (macaque) | J Infect Dis | Weekly TDF gave partial protection against repeated rectal SHIV challenges in rhesus macaques |
| 26743846 | 2016 | Preclinical (macaque) | J Infect Dis | Oral FTC/TDF prevented vaginal SHIV infection even in macaques co-infected with Chlamydia and Trichomonas |
| 23633402 | 2013 | Preclinical (macaque) | J Infect Dis | FTC/TDF was tested as prophylaxis against a tenofovir-resistant (K65R) SHIV |
| 24043812 | 2013 | Preclinical (macaque) | PNAS | A TDF-eluting intravaginal ring completely protected macaques from multiple vaginal SHIV challenges |
| 27275923 | 2016 | Preclinical (macaque) | PLoS One | Pod-intravaginal rings delivering TDF and FTC protected macaques from repeated SHIV exposures |
| 16810108 | 2006 | Preclinical (infant macaque) | J Acquir Immune Defic Syndr | Oral TDF and topical GS-7340 were evaluated against repeated oral SIV challenges in infant macaques |
| 12404171 | 2002 | Preclinical (infant macaque) | J Infect Dis | Low-dose topical (oral) TDF was tested for protecting infant macaques against SIV exposure |
| 36365101 | 2022 | Preclinical (macaque) | Pharmaceutics | Pharmacological validation of long-term TDF, emtricitabine and dolutegravir treatment in SIV-infected macaques |
| 22964889 | 2012 | Review | Curr Opin HIV AIDS | Lessons from animal models of antiretroviral prophylaxis and next steps in preclinical PrEP research |
| 14557287 | 2003 | Review | Clin Microbiol Rev | Acyclic nucleoside phosphonates, including tenofovir, are active against DNA viruses and retroviruses in cell culture, animals and clinical studies |
Singapore Market Information
All 7 licences are valid single-ingredient registrations. The five below are listed. The licence records contain no approved indication text.
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN15564P | TENOF Tenofovir Disoproxil Fumarate Film-Coated Tablets 300 mg | Film-coated tablet | — |
| SIN16566P | HOVID Tenofovir Disoproxil Fumarate Film-Coated Tablet 300 mg | Film-coated tablet | — |
| SIN15936P | VIRKIL Film-Coated Tablets 300 mg | Film-coated tablet | — |
| SIN13938P | Viread Tablets 300 mg | Film-coated tablet | — |
| SIN16078P | VIRCLEAN F.C. Tablets 300 mg | Film-coated tablet | — |
Safety Considerations
- Contraindication signals from the knowledge graph (not label text): The drug-disease graph used by the model links tenofovir disoproxil to several conditions. The most clinically relevant are kidney disease, Fanconi renotubular syndrome, hypophosphatemia, osteomalacia, rickets, lactic acidosis, liver disease and liver failure, fatty liver disease, and hepatitis C virus infection. The graph also lists QT-related conditions (long QT syndrome, torsades de pointes) and several psychiatric and neurological conditions. These signals should be checked against the official labelling before any conclusion is drawn.
- Literature-based concerns: The reviewed literature repeatedly points to renal and bone effects with long-term tenofovir disoproxil use.
Please refer to the package insert for authoritative warnings, contraindications and drug interaction information.
Conclusion and Next Steps
Decision: Hold
Rationale: The SIV prediction has a very high model score, but the evidence consists only of animal studies and reviews, with no clinical trials. SIV is not a human indication, and the finding duplicates the already approved HIV use, so it offers no new patient benefit.
To proceed, the following is needed:
- A clear human disease target. The data compiled for this report suggest re-framing toward established HIV prevention and treatment questions, or toward hepatitis B, where Phase 3 randomised evidence already exists. That indication is already approved and would be confirmatory rather than new.
- Mechanism of action data from DrugBank.
- Package insert warnings and contraindications from the HSA, so that safety screening can proceed.
- A renal and bone safety monitoring plan, and consideration of tenofovir alafenamide for at-risk patients.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.