Tenofovir Disoproxil

證據等級: L5

預測適應症: 4 個

Tenofovir Disoproxil: From Antiretroviral Therapy (HIV) to Simian Immunodeficiency Virus Infection

One-Sentence Summary

Tenofovir disoproxil is a nucleotide reverse transcriptase inhibitor (NRTI) prodrug used clinically for HIV antiretroviral therapy. The TxGNN model predicts a strong association with Simian Immunodeficiency Virus (SIV) Infection, supported by 2 clinical trials and 19 publications — however, the underlying evidence largely reconfirms tenofovir's already-known role in HIV/SIV pre-exposure prophylaxis (PrEP) in nonhuman primate models, rather than pointing to a novel human indication.

Quick Overview

Item	Content
Original Indication	Not available — drug has no license record in Norway (0 authorizations); clinically known as part of HIV antiretroviral therapy per underlying evidence
Predicted New Indication	Simian Immunodeficiency Virus (SIV) Infection
TxGNN Prediction Score	99.95%
Evidence Level	L3
Norway Market Status	✗ Not Marketed
Number of Authorizations	0
Recommended Decision	Hold

Why is This Prediction Reasonable?

Currently, detailed mechanism of action data is not available (data gap, DrugBank query pending). Based on the evidence pack's own repurposing rationale, tenofovir disoproxil is the oral prodrug of tenofovir (PMPA), a nucleotide reverse transcriptase inhibitor that blocks the reverse transcriptase enzyme shared across lentiviruses.

SIV and HIV both belong to the lentivirus genus and use structurally similar reverse transcriptase enzymes, which is why tenofovir's antiviral activity extends mechanistically from HIV to SIV. This mechanistic overlap has been extensively validated in nonhuman primate PrEP/PEP (pre- and post-exposure prophylaxis) models over the past two decades.

However, the evidence pack explicitly flags an important caveat: SIV infection is a nonhuman primate/veterinary disease model, not a human clinical indication. The underlying literature does not represent a new repurposing opportunity for human patients — it is preclinical validation of tenofovir's already-established HIV PrEP mechanism, observed in the animal model used to study it. The same caveat applies to the rank-2 prediction (feline AIDS/FIV), which is a veterinary-only indication.

Clinical Trial Evidence

Trial Number	Phase	Status	Enrollment	Key Findings
NCT00863668	Phase NA	Withdrawn	0	Studied HIV RNA decay kinetics using raltegravir (not tenofovir); withdrawn with zero enrollment — low relevance
NCT03577782	Phase 1/2	Unknown	12	Vedolizumab + antiretroviral therapy for HIV virological remission; tenofovir not the study drug, status unknown — low relevance

Note: Both trials were graded "C" (low relevance) in the underlying evidence assessment — neither directly tests tenofovir disoproxil against SIV infection.

Literature Evidence

PMID	Year	Type	Journal	Key Findings
20874040	2010	Review	Pharmacotherapy	Reviews systemic pre-exposure prophylaxis (PrEP) strategies for HIV prevention
27465645	2016	Animal Study	J Infect Dis	TAF + FTC combination protects macaques from rectal SHIV infection
36477356	2022	Animal Study	JCI Insight	Hypo-osmolar rectal tenofovir douche formulation prevents SHIV acquisition in macaques
16810108	2006	Animal Study	J Acquir Immune Defic Syndr	Oral TDF and topical GS-7340 protect infant macaques against repeated oral SIV challenge
16960777	2006	Animal Study	J Infect Dis	TDF chemoprophylaxis provides partial protection against SHIV in macaques with multiple challenges
22072766	2012	Animal Study	J Virol	Vaginal 1% tenofovir gel provides durable protection against SHIV infection in macaques
26743846	2016	Animal Study	J Infect Dis	FTC/TDF prevents vaginal SHIV infection even with chlamydia/trichomonas co-infection
38134382	2024	Animal Study	J Infect Dis	TAF/elvitegravir vaginal inserts extend postexposure protection against SHIV in macaques
23633402	2013	Animal Study	J Infect Dis	FTC/TDF prophylaxis effective even against tenofovir-resistant SHIV (K65R mutation)
14557287	2003	Review	Clin Microbiol Rev	Clinical potential of acyclic nucleoside phosphonates (cidofovir, adefovir, tenofovir) against DNA virus/retrovirus infections

Norway Market Information

Currently no authorization records — tenofovir disoproxil is not marketed in Norway under this evidence pack (0 licenses on file).

Safety Considerations

Please refer to the package insert for safety information. (Key warnings, contraindications, and drug-interaction data are not currently available in this evidence pack — flagged as a Blocking data gap requiring TFDA/official prescribing information before any S1 safety evaluation can proceed.)

Conclusion and Next Steps

Decision: Hold

Rationale: None of the four TxGNN-predicted indications represent a genuine, actionable human repurposing opportunity: the top two (SIV infection, feline AIDS) are animal/veterinary disease models that merely reconfirm tenofovir's already-known antiretroviral mechanism in nonhuman hosts, while the remaining two (a rare neurodevelopmental disorder and an obsolete hyperlipidemia term) have no supporting evidence and are flagged L5 (model prediction only). In addition, safety data required for even a preliminary review is missing (Blocking gap).

To proceed, the following is needed:

Official TFDA/manufacturer prescribing information (warnings, contraindications) — currently a Blocking gap (DG001)
Confirmed mechanism-of-action data from DrugBank — currently a High-severity gap (DG002)
Clarification of Norway regulatory/market status, since 0 licenses are currently on file
If pursued further, reframe the search toward genuinely novel human indications, since the current top candidates only validate tenofovir's established HIV/PrEP mechanism in animal models
Disclaimer

This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.