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
- Australia 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 oral antiviral originally used for chronic hepatitis B virus infection and HIV infection (including AIDS). The TxGNN model predicts it may be effective for simian immunodeficiency virus (SIV) infection, which is a primate counterpart of HIV rather than a new human disease. Support is limited to 0 registered clinical trials and animal-model and review publications (mostly macaque studies).
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Chronic hepatitis B virus infection; HIV infection; AIDS |
| Predicted New Indication | Simian immunodeficiency virus infection |
| TxGNN Prediction Score | 0.9995 |
| Evidence Level | L4 (preclinical studies only) |
| Australia Market Status | Listed on the PBS Schedule (1 of 1 items) – TGA (ARTG) registration status is not included in this data |
| Number of PBS Items | 1 (valid: 1) |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available in the data compiled for this report. Tenofovir is known to be a nucleotide reverse transcriptase inhibitor. Its efficacy in HIV and hepatitis B is established, and mechanistically it may be applicable to SIV.
SIV is the primate lentivirus counterpart of HIV-1 and also relies on reverse transcriptase. A nucleotide reverse transcriptase inhibitor is therefore expected to inhibit SIV replication. The retrieved literature is consistent with this. It consists mainly of macaque studies of pre-exposure prophylaxis (PrEP), prophylaxis in infant macaques, and antiretroviral therapy.
Important caveat: SIV infection in macaques is an animal model of an already-approved human indication (HIV). The evidence supports mechanism and dosing but is not a distinct human indication. The model’s other high-scoring predictions are also not new human opportunities:
- Hepatitis B virus infection is already an approved indication.
- AIDS related complex is a historical term overlapping with the approved HIV indication.
- Feline AIDS is a veterinary indication.
- Several rare tumour and genetic disorder predictions have no supporting evidence.
Clinical Trial Evidence
Currently no related clinical trials registered for SIV infection. No ANZCTR identifiers were found.
Literature Evidence
All studies below are preclinical (animal) work, reviews, or one human pharmacokinetic trial. None is a human efficacy RCT for this indication.
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 16960777 | 2006 | Animal study | J Infect Dis | Weekly tenofovir disoproxil fumarate (TDF) gave partial protection against repeated rectal SHIV challenges in macaques |
| 26743846 | 2016 | Animal study | J Infect Dis | Emtricitabine/TDF prevented vaginal SHIV infection in macaques coinfected with Chlamydia and Trichomonas |
| 23633402 | 2013 | Animal study | J Infect Dis | Emtricitabine/TDF PrEP was tested against a tenofovir-resistant SHIV (K65R mutation) in macaques |
| 24043812 | 2013 | Animal study | PNAS | A TDF-eluting intravaginal ring protected macaques from multiple vaginal SHIV challenges |
| 16810108 | 2006 | Animal study | J Acquir Immune Defic Syndr | Oral TDF and topical tenofovir GS-7340 were evaluated against repeated oral SIV challenges in infant macaques |
| 12404171 | 2002 | Animal study | J Infect Dis | Low-dose topical (oral) TDF was tested for protecting infant macaques from repeated low-dose oral SIV exposure |
| 24914761 | 2014 | Animal study | AIDS Res Hum Retroviruses | Combining a virus-like particle HIV vaccine with partially protective oral PrEP prevented SHIV infection in macaques |
| 22964889 | 2012 | Review | Curr Opin HIV AIDS | Reviews lessons from animal models of antiretroviral PrEP and next steps in preclinical research |
| 14557287 | 2003 | Review | Clin Microbiol Rev | Reviews acyclic nucleoside phosphonates (cidofovir, adefovir, tenofovir) against DNA virus and retrovirus infections |
| 21896911 | 2011 | Human PK trial | Antimicrob Agents Chemother | Single-dose TDF and TDF-emtricitabine pharmacokinetics and safety in HIV-infected pregnant women and their infants |
Australia Market Information
| ARTG Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| ARTG 10310P | Tenofovir Sandoz | Tablet containing tenofovir disoproxil fumarate 300 mg (oral) | Indication text not specified in the data compiled for this report |
Safety Considerations
- Knowledge-graph contraindication signals (not label text): The TxGNN knowledge graph links tenofovir disoproxil to the following conditions. These are model-derived associations and should be verified against the approved label.
- Renal and hepatic: kidney disease, liver disease, liver failure, fatty liver disease and non-alcoholic steatohepatitis, lactic acidosis, Fanconi renotubular syndrome.
- Bone and metabolic: hypophosphatemia, osteomalacia, rickets, hypertriglyceridemia, obesity disorder.
- Cardiac and neuropsychiatric: long QT syndrome and torsades de pointes, epilepsy, anxiety and related disorders, delusional disorder, paranoid schizophrenia.
- Other: gallbladder disease, hepatitis C virus infection.
- Drug Interactions: No interaction records were found in the data compiled.
Please refer to the TGA-approved Product Information (PI) for authoritative warnings, contraindications and interaction information.
Conclusion and Next Steps
Decision: Hold
Rationale:
- Evidence is preclinical only (L4). There are no registered clinical trials for SIV infection, and the indication is an animal model of the already-approved HIV indication, not a distinct human indication.
- The model score is very high (0.9995), but it does not translate into a new clinical opportunity.
To proceed, the following is needed:
- Confirmation of whether any human indication is being pursued. For SIV, the practical value is as a preclinical model to support dosing and prophylaxis research, not a new patient indication.
- Detailed mechanism of action data (MOA).
- The approved indication text and safety information (warnings, contraindications) from the TGA Product Information for ARTG 10310P.
- Review of the model’s human-relevant predictions separately. Hepatitis B is already approved, and a Phase 3 RCT (NCT01745822, perinatal HBV transmission) supports that use. Any such review should include monitoring of renal function and bone density.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.