Tenofovir Disoproxil
| Evidence Level: L3 | Predicted Indications: 4 |
Table of Contents
- Tenofovir Disoproxil
- Tenofovir Disoproxil: From HIV Infection to Simian Immunodeficiency Virus (SIV) Infection
Tenofovir Disoproxil: From HIV Infection to Simian Immunodeficiency Virus (SIV) Infection
One-Sentence Summary
Tenofovir disoproxil is a nucleotide reverse transcriptase inhibitor (NRTI) established as an antiretroviral agent against HIV infection. The TxGNN model predicts it may be effective for Simian Immunodeficiency Virus (SIV) infection, with 2 clinical trials and 20 publications currently identified — however, this indication describes a non-human primate disease model rather than a distinct human condition, and the supporting evidence largely reflects decades of preclinical validation of tenofovir’s already-known anti-lentiviral mechanism rather than a genuinely novel human therapeutic use.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not recorded in structured licensing data; literature evidence consistently identifies the drug as an antiretroviral used for HIV-1 infection (nucleotide reverse transcriptase inhibitor) |
| Predicted New Indication | Simian Immunodeficiency Virus (SIV) Infection |
| TxGNN Prediction Score | 99.95% |
| Evidence Level | L3 |
| UK Market Status | Not marketed |
| Number of Marketing Authorisations | 0 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available in structured form (data gap). Based on the supporting rationale in the Evidence Pack, tenofovir is a nucleotide reverse transcriptase inhibitor that blocks viral DNA synthesis — a mechanism that is well established for HIV-1 and has been extensively used in human antiretroviral therapy and pre-exposure prophylaxis (PrEP).
SIV and HIV both belong to the Lentivirus genus and share highly homologous reverse transcriptase enzymes. This close structural relationship explains the very high mechanistic transferability captured by the TxGNN model: an agent that inhibits HIV reverse transcriptase would be expected, on molecular grounds, to inhibit SIV reverse transcriptase equally well.
However, this mechanistic plausibility should be interpreted with caution. SIV infection is not an independent human disease — it is the standard non-human primate (macaque) model used specifically to study HIV pathogenesis and to validate antiretroviral and PrEP strategies before human application. Nearly all of the identified evidence for this “predicted indication” in fact represents decades of animal-model research confirming tenofovir’s already-established anti-HIV activity, rather than evidence of a new therapeutic application in humans. The prediction should therefore be read as a validation of known pharmacology within an animal model, not as a novel repurposing opportunity for clinical practice.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrolment | Key Findings |
|---|---|---|---|---|
| NCT00863668 | N/A | Withdrawn | 0 | Studied HIV RNA decay kinetics with raltegravir (not tenofovir) in the context of SIV-macaque decay comparisons; trial withdrawn with zero enrolment — low relevance (mismatched drug) |
| NCT03577782 | Phase 1/2 | Unknown | 12 | Evaluated vedolizumab combined with antiretroviral therapy for HIV virological remission in humans, not the SIV animal model — low relevance (species mismatch) |
Both trials were assessed as low relevance (Grade C) to the specific SIV infection indication, reflecting either drug mismatch or a human-HIV vs animal-SIV mismatch.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 20874040 | 2010 | Review | Pharmacotherapy | Reviews systemic pre-exposure prophylaxis (PrEP) evidence for HIV infection in humans, underpinning the rationale for tenofovir’s antiretroviral use |
| 36477356 | 2022 | Animal study (macaque) | JCI Insight | Hypo-osmolar rectal tenofovir douche formulation prevented SHIV acquisition in macaques |
| 27465645 | 2016 | Animal study (macaque) | J Infect Dis | Oral emtricitabine/tenofovir alafenamide protected macaques from rectal SHIV infection |
| 22072766 | 2012 | Animal study (macaque) | J Virol | Vaginal 1% tenofovir gel provided durable protection against SHIV in macaques |
| 26743846 | 2016 | Animal study (macaque) | J Infect Dis | Emtricitabine/tenofovir disoproxil fumarate prevented vaginal SHIV infection despite co-infections |
| 16810108 | 2006 | Animal study (infant macaque) | JAIDS | Oral tenofovir disoproxil fumarate protected infant macaques against repeated oral SIV challenge |
| 16960777 | 2006 | Animal study (macaque) | J Infect Dis | Tenofovir disoproxil fumarate provided partial protection against SHIV in macaques with multiple challenges |
| 38134382 | 2024 | Animal study (macaque, PEP) | J Infect Dis | Tenofovir alafenamide/elvitegravir vaginal inserts extended post-exposure protection against SHIV in macaques |
| 39632836 | 2024 | Animal study (macaque) | Nature Communications | Early ART with long-acting antivirals achieved SHIV remission in macaques |
| 23633402 | 2013 | Animal study (macaque) | J Infect Dis | Emtricitabine/tenofovir disoproxil fumarate prevented transmission of a tenofovir-resistant SHIV strain (K65R mutation) in macaques |
UK Market Information
No UK marketing authorisation is currently on record for this drug in this Evidence Pack (total_licenses = 0). This preparation is currently classed as not marketed in the UK per available data.
Safety Considerations
Please refer to the SmPC and BNF for safety information. Report suspected adverse reactions via the Yellow Card Scheme.
Conclusion and Next Steps
Decision: Hold
Rationale: The predicted indication, SIV infection, is a non-human primate disease model rather than an independent human condition, and the identified clinical trial evidence shows low relevance (species/drug mismatches). While the underlying mechanistic link between tenofovir and lentiviral reverse transcriptase is sound, the current evidence base largely reconfirms tenofovir’s known anti-HIV activity in animal models rather than supporting a genuinely new human therapeutic indication.
To proceed, the following is needed:
- Verified mechanism of action (MOA) documentation from a primary source (e.g. DrugBank), currently marked as a high-severity data gap
- Product labelling warnings and contraindications from the relevant regulatory authority, currently marked as a blocking data gap preventing initial safety screening (S1)
- Clarification of whether “SIV infection” should be reclassified as an animal-health/veterinary research target rather than a candidate for human drug repurposing, given the species mismatch
- Re-evaluation of the knowledge-graph output against lower-ranked candidates (feline immunodeficiency virus, neurodevelopmental disorder, obsolete hyperlipidaemia classification), which were independently flagged as low-confidence or likely knowledge-graph artefacts (L4–L5, Hold)
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.