Tenofovir Disoproxil

證據等級: L5

預測適應症: 4 個

Tenofovir Disoproxil: From HIV-1 Infection to Simian Immunodeficiency Virus Infection

One-Sentence Summary

Tenofovir disoproxil is a nucleotide reverse transcriptase inhibitor (NRTI) prodrug originally developed for the treatment of HIV-1 infection and chronic hepatitis B. The TxGNN model predicts it may be effective for Simian Immunodeficiency Virus (SIV) Infection, with 2 clinical trials and ~20 publications currently associated with this direction — however, the underlying evidence is almost entirely preclinical macaque pre-exposure prophylaxis (PrEP) research rather than treatment of SIV disease itself, and the two clinical trials identified are graded as low relevance (Grade C).

Quick Overview

Item	Content
Original Indication	Not documented in this evidence pack (data gap); clinically known to be HIV-1 infection / chronic hepatitis B
Predicted New Indication	Simian Immunodeficiency Virus Infection
TxGNN Prediction Score	99.95%
Evidence Level	L2 (per evidence pack scoring; underlying studies are largely preclinical animal models — see caveat below)
Germany 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 for tenofovir disoproxil in this evidence pack (data gap DG002). Based on known pharmacology, tenofovir disoproxil is a prodrug of tenofovir, an acyclic nucleotide analog that inhibits the reverse transcriptase enzyme shared across lentiviruses. This enzyme is highly conserved between HIV and SIV, which is the biological basis for the TxGNN association.

However, a close reading of the supporting evidence reveals an important mismatch: nearly all literature and trial evidence retrieved for "SIV infection" actually documents tenofovir's use as pre-exposure prophylaxis (PrEP) against HIV/SHIV transmission in macaque models, not treatment of an established SIV infection as a disease entity. In other words, the real-world therapeutic application this evidence supports (HIV PrEP) is already an approved use of tenofovir disoproxil-based regimens, not a genuinely novel indication. This label/evidence mismatch is explicitly flagged in the repurposing rationale and should be treated as a data-mapping artifact rather than a new repurposing opportunity.

Clinical Trial Evidence

Trial Number	Phase	Status	Enrollment	Key Findings
NCT00863668	NA	Withdrawn	0	Studied raltegravir (not tenofovir) HIV decay kinetics referencing SIV-macaque comparators; Grade C relevance — withdrawn, zero enrollment, wrong drug
NCT03577782	Phase 1/2	Unknown	12	Vedolizumab + ART for HIV virological remission; Grade C relevance — tenofovir not the primary intervention, unknown status, very small sample

Both identified trials were assessed as low relevance to the SIV infection indication specifically.

Literature Evidence

PMID	Year	Type	Journal	Key Findings
20874040	2010	RCT	Pharmacotherapy	Systemic pre-exposure prophylaxis for HIV infection — foundational PrEP evidence base
18216122	2008	Review	J Virol	SIVagm dynamics in African green monkeys treated with tenofovir + emtricitabine ART
27465645	2016	Cohort (macaque)	J Infect Dis	TAF + FTC protects macaques from rectal SHIV infection (PrEP model)
36477356	2022	Cohort (macaque)	JCI Insight	Hypo-osmolar rectal tenofovir douche prevents SHIV acquisition
16810108	2006	Cohort (macaque)	J Acquir Immune Defic Syndr	Oral TDF and topical GS-7340 protect infant macaques against oral SIV challenge
16960777	2006	Cohort (macaque)	J Infect Dis	TDF chemoprophylaxis gives partial protection against SHIV with multiple challenges
22072766	2012	Cohort (macaque)	J Virol	Vaginal 1% tenofovir gel provides durable protection from SHIV infection
26743846	2016	Cohort (macaque)	J Infect Dis	FTC/TDF prevents vaginal SHIV infection even with concurrent STIs
38134382	2024	Cohort (macaque)	J Infect Dis	TAF/elvitegravir vaginal inserts give extended postexposure SHIV protection
23633402	2013	Cohort (macaque)	J Infect Dis	FTC/TDF prevents transmission of tenofovir-resistant (K65R) SHIV

Note: All except the two entries above are animal-model PrEP/prophylaxis studies, not treatment studies of established SIV disease.

Germany Market Information

Tenofovir disoproxil is currently not marketed under this dataset (total_licenses = 0), so no authorization records are available to list.

Safety Considerations

Safety data (key warnings, contraindications, and drug-drug interactions) is currently unavailable in this evidence pack. This is tracked internally as data gap DG001 (Blocking severity) — the absence of TFDA/regulatory label information (warnings and contraindications) prevents this candidate from progressing to Stage 1 (S1) safety review. This gap must be closed via TFDA/EMA label retrieval before any further evaluation.

Conclusion and Next Steps

Decision: Hold

Rationale: The predicted indication label ("SIV infection") does not match the substance of its supporting evidence, which almost entirely documents tenofovir's established HIV PrEP mechanism in animal models rather than a genuinely novel therapeutic application. Combined with a Blocking-severity safety data gap (DG001) and the drug's current unmarketed status, there is insufficient basis to advance this candidate.

To proceed, the following is needed:

Resolve DG001: obtain TFDA/EMA package insert data (warnings, contraindications) to enable S1 safety review
Resolve DG002: confirm mechanism of action via DrugBank to properly assess mechanistic plausibility
Clarify with the modeling/evidence pipeline whether "SIV infection" should be re-mapped to the already-approved human HIV PrEP indication, since current evidence does not support it as a distinct new indication
Note: lower-ranked predictions (feline AIDS — veterinary-only evidence; two neurological/metabolic disease predictions with zero supporting evidence, L5) should remain on Hold and are not recommended for further evaluation at this time
Disclaimer

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