Tenofovir Disoproxil
| Evidence Level: L4 | Predicted Indications: 4 |
Table of Contents
- Tenofovir Disoproxil
- Pharmacist Assessment Report
- Tenofovir Disoproxil: From Chronic Hepatitis B and HIV Infection to Simian Immunodeficiency Virus Infection
- One-Sentence Summary
- Quick Overview
- Why is This Prediction Reasonable?
- Clinical Trial Evidence
- Literature Evidence
- India Market Information
- Safety Considerations
- Conclusion and Next Steps
- Disclaimer
Tenofovir Disoproxil: From Chronic Hepatitis B and HIV Infection to Simian Immunodeficiency Virus Infection
One-Sentence Summary
Tenofovir disoproxil is an antiviral originally used to treat chronic hepatitis B virus infection, HIV infection and AIDS. The TxGNN model predicts it may be effective for simian immunodeficiency virus infection, but this is an animal-model disease, supported by 0 registered clinical trials and 20 publications (mostly preclinical macaque studies and reviews). The data therefore mainly reinforce the existing HIV indication rather than point to a new human indication.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Chronic hepatitis B virus infection, HIV infectious disease, AIDS (the Indian licence records contain no approved-indication text) |
| Predicted New Indication | Simian immunodeficiency virus infection |
| TxGNN Prediction Score | 0.9995 |
| Evidence Level | L4 |
| India Market Status | Listed in a compiled Indian medicine price dataset (at least 20) – CDSCO approval status is not included in this data |
| Number of Listed Products | at least 20 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available. Based on known information, tenofovir disoproxil is a nucleotide reverse transcriptase inhibitor. Its efficacy in HIV and hepatitis B is established, and mechanistically it may be applicable to related retroviruses.
Simian immunodeficiency virus (SIV) and the chimeric SHIV are lentiviruses closely related to HIV-1 and use the same reverse transcriptase target. Macaque studies show partial to substantial protection against SIV/SHIV acquisition with tenofovir disoproxil fumarate (TDF), alone or combined with emtricitabine.
However, SIV infection is a preclinical or veterinary model, not a human disease. The prediction is biologically sensible, but it validates the existing HIV indication rather than creating a new one for patients.
Other predictions from the model are weaker:
- Feline acquired immunodeficiency syndrome: a veterinary indication with a single 2023 publication (combination antiretroviral therapy in FIV-infected cats). It has limited value for human repurposing.
- Neurodevelopmental disorder with ataxic gait, absent speech, and decreased cortical white matter: score 0.9995, but no trials, no literature and no plausible mechanistic link. It is likely a TxGNN model (deep learning) artefact.
- Obsolete familial combined hyperlipidemia: no evidence, the disease term is obsolete, and tenofovir has no lipid-lowering mechanism.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
The most relevant publications are listed below. All are preclinical or review articles, and no randomised controlled trials in humans were identified.
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 16960777 | 2006 | Preclinical (macaque) | J Infect Dis | TDF chemoprophylaxis gave partial protection against repeated SHIV challenges |
| 26743846 | 2016 | Preclinical (macaque) | J Infect Dis | Emtricitabine/TDF prevented vaginal SHIV infection despite coinfection with Chlamydia and Trichomonas |
| 16810108 | 2006 | Preclinical (macaque) | J Acquir Immune Defic Syndr | Oral TDF and topical GS-7340 evaluated in infant macaques against repeated oral SIV challenges |
| 12404171 | 2002 | Preclinical (macaque) | J Infect Dis | Topical low-dose TDF tested in infant macaques against repeated low-dose oral SIV exposures |
| 24043812 | 2013 | Preclinical (macaque) | PNAS | TDF-eluting intravaginal ring completely protected macaques from multiple vaginal SHIV challenges |
| 23633402 | 2013 | Preclinical (macaque) | J Infect Dis | Oral emtricitabine/TDF PrEP tested against tenofovir-resistant (K65R) SHIV |
| 24914761 | 2014 | Preclinical (macaque) | AIDS Res Hum Retroviruses | VLP HIV vaccine plus partially protective oral PrEP prevented SHIV infection |
| 20497048 | 2010 | Preclinical (macaque) | J Infect Dis | In SIV-infected macaques, HAART reduced CNS viral replication and inflammation, but viral DNA persisted |
| 14557287 | 2003 | Review | Clin Microbiol Rev | Acyclic nucleoside phosphonates (cidofovir, adefovir, tenofovir) are active against DNA viruses and retroviruses |
| 20874040 | 2010 | Review | Pharmacotherapy | Overview of systemic pre-exposure prophylaxis for HIV |
India Market Information
Twenty valid single-ingredient licences are registered. Five main ones are shown below. The licence records contain no approved-indication text.
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| 219209 | Tenfoclear 300mg Tablet (Abbott) | Bottle of 30 tablets | Not stated in the licence record |
| 214916 | Tenvir Tablet (Cipla Ltd) | Bottle of 30 tablets | Not stated in the licence record |
| 217770 | Tenof Tablet (Hetero Drugs Ltd) | Strip of 30 tablets | Not stated in the licence record |
| 184862 | Ricovir 300mg Tablet (Mylan Pharmaceuticals Pvt Ltd) | Bottle of 30 tablets | Not stated in the licence record |
| 182888 | Qvir Kit (Cipla Ltd) | Packet of 1 kit | Not stated in the licence record |
Safety Considerations
The data compiled for this report contain no package-insert warnings, contraindications or drug-interaction records. Please refer to the package insert for safety information.
The knowledge graph links the drug to a number of conditions as potential contraindications. These come from graph edges, not label text, and should be verified against the label. The main groups are:
- Cardiac rhythm: long QT syndrome, familial long QT syndrome, torsades de pointes
- Liver: liver failure, liver disease, fatty liver disease, non-alcoholic steatohepatitis, gallbladder disease, hepatitis C virus infection
- Kidney and bone/mineral: kidney disease, Fanconi renotubular syndrome, hypophosphatemia, osteomalacia, rickets
- Metabolic: lactic acidosis, hypertriglyceridemia, obesity
- Neuropsychiatric: epilepsy, anxiety disorder, dysthymic disorder, delusional disorder, paranoid schizophrenia
Conclusion and Next Steps
Decision: Hold
Rationale: The prediction rests only on preclinical macaque studies and reviews (evidence level L4), with no clinical trials. SIV infection is an animal model, so the findings support the existing HIV indication rather than a new human one. The other predicted indications have little or no supporting evidence.
To proceed, the following is needed:
- A clear human-disease target, since SIV and feline AIDS are not human indications. Any repurposing work should look at other human conditions.
- Mechanism of action data for tenofovir disoproxil, which is not available.
- Package insert warnings and contraindications from the Indian regulator, which are required before safety screening can proceed.
- Review of the knowledge-graph contraindication signals (liver, kidney, bone and QT-related) against the label.
- Remapping of the obsolete disease term (familial combined hyperlipidemia) and verification of the unsupported rare neurodevelopmental prediction before any further consideration.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.