Lopinavir

證據等級: L5

預測適應症: 3 個

Lopinavir: From HIV-1 Infection to Simian Immunodeficiency Virus Infection

One-Sentence Summary

Lopinavir is an HIV-1 protease inhibitor, typically co-formulated with ritonavir (LPV/RTV) as part of antiretroviral therapy — this is confirmed only indirectly through the supporting literature in this evidence pack, since detailed original indication and mechanism-of-action data are not currently available. The TxGNN model predicts activity against simian immunodeficiency virus (SIV) infection, an HIV-related lentivirus that infects non-human primates, supported by 0 clinical trials and 3 preclinical publications. Because the predicted indication is an animal disease rather than a human condition, and core safety data are missing, this candidate requires substantial additional validation before any clinical consideration.

Quick Overview

Item	Content
Original Indication	Not available in evidence pack (inferred from literature context as HIV-1 antiretroviral therapy — see Data Gap DG002)
Predicted New Indication	Simian immunodeficiency virus infection
TxGNN Prediction Score	99.90%
Evidence Level	L4 (preclinical/mechanism studies only, non-human primate models)
Finland Market Status	未上市 (Not marketed)
Number of Authorizations	0
Recommended Decision	Hold

Why is This Prediction Reasonable?

Detailed mechanism-of-action data for lopinavir is not currently available in this evidence pack (Data Gap DG002, severity: High). Based on the supporting literature retrieved, lopinavir is used in combination with ritonavir (LPV/RTV) as an antiretroviral regimen "as recommended in humans" (per PMID 12951220), consistent with its known role as an HIV-1 protease inhibitor.

SIV is the simian counterpart of HIV — both are primate lentiviruses with closely related viral protease structures, which is the mechanistic basis TxGNN likely used to link lopinavir to this indication. The three supporting publications describe LPV/RTV-containing antiretroviral regimens being tested in macaques experimentally infected with SIV or SHIV (chimeric SIV/HIV) as translational models for evaluating protease inhibitor efficacy — not as a proposed human therapy for a naturally occurring human disease.

Important caveat: SIV infection is a disease of non-human primates, not a human condition. This prediction should be interpreted as validating lopinavir's established antiretroviral/protease-inhibitory mechanism within animal HIV-model research, rather than as a novel human repurposing opportunity. The same caution applies more strongly to the rank 2 prediction (feline acquired immunodeficiency syndrome, a cat-specific disease) and rank 3 (a human neurodevelopmental genetic disorder with no supporting evidence or clear mechanistic link to protease inhibition).

Clinical Trial Evidence

Currently no related clinical trials registered

Literature Evidence

PMID	Year	Type	Journal	Key Findings
16973590	2006	Preclinical (macaque model)	Journal of Virology	Studied viral decay kinetics in SIVmac251-infected cynomolgus macaques receiving a 7-day quadruple antiretroviral regimen
17350308	2007	Preclinical (macaque model)	Microbes and Infection	Constructed a chimeric SHIV bearing the HIV-1 protease gene to enable in vivo testing of protease inhibitors in rhesus macaques
12951220	2003	Preclinical (macaque model)	Journal of Virological Methods	Evaluated oral HAART (AZT + 3TC + Lopinavir/Ritonavir, human-recommended dosing) effects on CD8 subsets in SHIV(89.6P)-infected macaques

Safety Considerations

Please refer to the package insert for safety information.

(Note: TFDA warning/contraindication data is flagged as a Blocking data gap (DG001) — this must be resolved before any safety-based decision can be made.)

Conclusion and Next Steps

Decision: Hold

Rationale: The predicted indication (SIV infection) is a disease of non-human primates rather than a human condition, so the current evidence — while mechanistically plausible given lopinavir's known protease-inhibitor class — does not translate into an actionable human repurposing opportunity. Combined with a Blocking safety data gap and the drug's unmarketed status in Finland, there is insufficient basis to proceed.

To proceed, the following is needed:

TFDA/regulatory package insert warnings and contraindications (Data Gap DG001, Blocking)
Confirmed original indication and mechanism-of-action data for lopinavir (Data Gap DG002)
Reassessment of whether any of the three predicted indications have a genuine human-relevant analog worth pursuing (SIV → HIV-related human indications, if any; FIV and the neurodevelopmental disorder currently show no mechanistic or evidentiary support)
If pursuing an HIV-adjacent human indication, dedicated clinical trial and literature search using human-relevant disease terms rather than the animal-model terms currently predicted
Disclaimer

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