Lopinavir

證據等級: L5

預測適應症: 10 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 (Kaletra/Aluvia), that blocks viral maturation and has been a cornerstone of antiretroviral therapy — though it is not currently registered in Singapore. The TxGNN model predicts it may be effective for Simian Immunodeficiency Virus (SIV) Infection, with 0 clinical trials and 3 animal study publications currently supporting this direction.

Quick Overview

Item	Content
Original Indication	Not registered in Singapore; established HIV-1 protease inhibitor
Predicted New Indication	Simian Immunodeficiency Virus (SIV) Infection
TxGNN Prediction Score	99.90%
Evidence Level	L4
Singapore Market Status	Not marketed
Number of Registrations	0
Recommended Decision	Hold

Why is This Prediction Reasonable?

Lopinavir inhibits the HIV-1 aspartyl protease, preventing cleavage of the Gag-Pol polyprotein during viral assembly. Without this processing step, immature, non-infectious virions are produced. It is invariably co-administered with ritonavir, a CYP3A4 inhibitor that acts as a pharmacokinetic booster to sustain therapeutically effective lopinavir plasma concentrations.

The rationale for an SIV prediction rests on structural analogy: SIV possesses a homologous aspartyl protease, but its amino-acid sequence diverges substantially from HIV-1. This divergence means lopinavir's binding affinity to wild-type SIV protease is considerably weaker than to its intended HIV-1 target — making direct clinical translation uncertain. A key nuance in the evidence is that the animal studies available involve SHIV (chimeric SIV constructs that carry the HIV-1 protease gene inserted into an SIV backbone), not authentic wild-type SIV. In SHIV models, lopinavir activity is expected and mechanistically predictable; for wild-type SIV, efficacy remains unestablished.

The very high TxGNN prediction score most likely reflects knowledge-graph co-clustering of HIV and SIV nodes — a network topology signal — rather than a confirmed pharmacological signal against wild-type SIV protease. The mechanistic connection is indirect analogy, not direct biological equivalence.

Clinical Trial Evidence

Currently no related clinical trials registered.

Literature Evidence

PMID	Year	Type	Journal	Key Findings
16973590	2006	Animal Study (Macaque)	Journal of Virology	Quadruple ART including lopinavir produced rapid viral decay in cynomolgus macaques infected with SIVmac251, modelling HIV-1 kinetic parameters
12951220	2003	Animal Study (Macaque)	Journal of Virological Methods	Oral LPV/r + AZT + 3TC (HAART) modulated peripheral CD8 subsets in SHIV(89.6P)-infected rhesus macaques; LPV/r active in chimeric SHIV model
17350308	2007	Animal Model Construction	Microbes and Infection	Construction of SHIV-pr carrying HIV-1 protease gene; viral growth completely blocked by peptide-analog PI in vitro; weak persistent viremia in inoculated macaques

Singapore Market Information

Lopinavir has no marketing authorizations on record with the Health Sciences Authority (HSA) of Singapore. The drug is classified as not marketed.

Safety Considerations

Please refer to the package insert for safety information.

Conclusion and Next Steps

Decision: Hold

Rationale: Evidence is confined to preclinical macaque studies using SHIV chimeric models (which incorporate the HIV-1 protease gene), rather than wild-type SIV, providing insufficient basis to advance lopinavir as a repurposing candidate for SIV infection in any clinical or translational context.

To proceed, the following is needed:

MOA clarification against wild-type SIV protease: quantitative inhibition data (IC₅₀ comparison: HIV-1 PR vs. SIV PR) to determine whether any biologically meaningful activity exists
Clarification of clinical intent: SIV infection is a non-human primate disease — if the downstream goal is primate research (e.g., vaccine model support) rather than human indication, a fundamentally different evaluation framework applies
Singapore (HSA) regulatory filing: obtain approved indications, full label warnings, and contraindication text to enable S1 safety screening
DrugBank MOA data: retrieve full mechanism-of-action, drug interaction, and toxicity profiles to complete the evidence dossier before any further development decision
Disclaimer

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