Lopinavir
| 證據等級: L5 | 預測適應症: 3 個 |
目錄
Using the evidence pack content directly (no fabricated data), here is the evaluation report:
Lopinavir: From HIV-1 Infection to Simian Immunodeficiency Virus (SIV) Infection
One-Sentence Summary
Lopinavir is an HIV-1 protease inhibitor, most familiar as a component of combination antiretroviral therapy for HIV-1 infection. The TxGNN model predicts a high similarity score for Simian Immunodeficiency Virus (SIV) Infection, but this “new indication” is not a human disease — it is the standard non-human primate model used to test HIV antiretrovirals — so the signal is currently supported only by 3 animal-model publications and zero clinical trials.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not documented in the evidence pack’s regulatory data (no taiwan_regulatory.licenses entries); based on the mechanistic rationale supplied with the prediction, Lopinavir is an HIV-1 protease inhibitor used in antiretroviral therapy |
| Predicted New Indication | Simian Immunodeficiency Virus (SIV) Infection |
| TxGNN Prediction Score | 99.90% |
| Evidence Level | L4 |
| Canada Market Status | ✗ Not Marketed |
| Number of DINs | 0 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed formal mechanism-of-action data is not available in the evidence pack (flagged as data gap DG002). Based on the rationale accompanying the prediction, Lopinavir is an HIV-1 protease inhibitor, and SIV protease shares high sequence/structural homology with HIV-1 protease — which is precisely why SIV-infected macaques are routinely used as a pre-clinical animal model for testing HIV antiretroviral drugs, including protease inhibitors like Lopinavir.
However, this mechanistic link needs to be read carefully: SIV infection is not a human disease. It is a veterinary/research condition confined to non-human primates. The three supporting publications describe Lopinavir (often as part of combination antiretroviral regimens) being used to suppress SIV/SHIV replication in macaques as a proxy for studying HIV-1 dynamics — not as evidence of a genuinely novel, independently actionable human indication.
In effect, this candidate largely reconfirms Lopinavir’s known antiretroviral mechanism via an animal-model term rather than surfacing a new treatable human condition. The two lower-ranked candidates in this evidence pack (feline acquired immunodeficiency syndrome, and a rare neurodevelopmental disorder) are similarly not clinically actionable: the former is a non-human disease with no supporting literature, and the latter shows no known biological pathway connecting HIV protease inhibition to neurodevelopmental pathology — both are flagged in the evidence pack as likely knowledge-graph embedding artifacts (L5, Hold) rather than real signals, and are not carried further in this report.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 16973590 | 2006 | Animal Study | Journal of Virology | Quadruple antiretroviral therapy in SIVmac251-infected cynomolgus macaques produced rapid viral decay, used to model HIV-1 viral dynamics |
| 17350308 | 2007 | Animal Study | Microbes and Infection | Constructed a novel SHIV carrying the HIV-1 protease gene in rhesus macaques as an in vivo tool for testing protease inhibitor efficacy |
| 12951220 | 2003 | Animal Study | Journal of Virological Methods | Oral HAART (AZT + 3TC + Lopinavir/Ritonavir) evaluated for impact on CD8 T-cell subsets in SHIV(89.6P)-infected rhesus macaques |
Canada Market Information
No Health Canada marketing authorizations (DINs) were found for this ingredient in the evidence pack — total_licenses = 0 and market status is recorded as Not Marketed.
Safety Considerations
Please refer to the package insert for safety information.
(Note: the evidence pack flags the absence of product-monograph warnings/contraindications as a Blocking data gap — DG001 — meaning this candidate cannot yet enter safety pre-screening (S1) regardless of the efficacy signal above.)
Conclusion and Next Steps
Decision: Hold
Rationale: The top-ranked predicted indication, SIV infection, is not a human disease and functions as an HIV-1 animal model rather than an independently actionable repurposing target; supporting evidence is limited to 3 animal studies (L4) with no clinical trials. Combined with the drug’s non-marketed status in Canada (0 DINs) and a Blocking data gap on safety/product-monograph information (DG001), this candidate is not ready to advance past S0.
To proceed, the following is needed:
- Resolve DG001 (Health Canada product monograph warnings/contraindications) — Blocking, required before any S1 safety pre-screening
- Resolve DG002 (formal mechanism-of-action documentation from DrugBank)
- Re-evaluate whether a clinically meaningful human indication (rather than the SIV animal-model term) should be pursued for this protease-inhibitor mechanism
- If pursued, obtain human clinical evidence (trials/RCTs) rather than relying on animal-model literature alone
- If repurposing is to move forward, assess the Health Canada regulatory pathway given the drug is currently not marketed in Canada
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.