Lopinavir

Evidence Level: L4

Predicted Indications: 3

Lopinavir

Pharmacist Assessment Report

Lopinavir: From HIV Infection to Simian Immunodeficiency Virus Infection

One-Sentence Summary

Lopinavir is an HIV-1 protease inhibitor, originally used to treat HIV infection and AIDS. The TxGNN model predicts it may be effective for simian immunodeficiency virus (SIV) infection, an animal disease with no human clinical indication. Support is limited to 3 preclinical publications in macaques and no registered clinical trials.

Quick Overview

Item	Content
Original Indication	HIV infectious disease; AIDS (the ARTG entry has no indication text)
Predicted New Indication	Simian immunodeficiency virus infection
TxGNN Prediction Score	0.9990
Evidence Level	L4
Australia Market Status	Listed on the PBS Schedule (1 of 1 items) – TGA (ARTG) registration status is not included in this data
Number of PBS Items	1 (valid: 1)
Recommended Decision	Hold

Why is This Prediction Reasonable?

Detailed mechanism of action data is not available in the data compiled for this report. Lopinavir is known to be an HIV-1 protease inhibitor. It is marketed as a fixed-dose combination with ritonavir (Kaletra, 200 mg/50 mg tablet), and its efficacy in HIV infection is established.

SIV is a closely related primate lentivirus with a structurally similar protease, so activity against it is mechanistically plausible. The supporting literature consists of macaque studies in which lopinavir was one component of antiretroviral combinations. This is indirect, preclinical-model evidence.

SIV infection is an animal disease and has no human clinical indication. The high TxGNN score probably reflects the similarity to the original HIV indication rather than a genuine new therapeutic opportunity. In practice, SIV and SHIV macaque models are mainly useful as research tools for testing antiretroviral regimens.

Two other predictions were also generated: feline acquired immunodeficiency syndrome (score 0.9990, no supporting studies, veterinary indication, and feline protease is less sensitive to HIV protease inhibitors) and a rare neurodevelopmental disorder with ataxic gait, absent speech and decreased cortical white matter (score 0.9990, no plausible mechanistic link, possibly a TxGNN model (deep learning) artefact). Neither is recommended for further action.

Clinical Trial Evidence

Currently no related clinical trials registered.

Literature Evidence

PMID	Year	Type	Journal	Key Findings
16973590	2006	Preclinical animal study	Journal of Virology	Four cynomolgus macaques infected with SIVmac251 received a 7-day course of quadruple antiretroviral therapy; study of rapid viral decay and viral dynamics compared with HIV-1
17350308	2007	Preclinical model development	Microbes and Infection	Construction of a novel SHIV carrying the HIV-1 protease gene, as a tool for in vivo testing of protease inhibitors in rhesus macaques
12951220	2003	Preclinical animal study	Journal of Virological Methods	Two SHIV 89.6P-infected rhesus macaques received oral AZT, 3TC and lopinavir/ritonavir for 28 days; impact on the CD8 subset assessed

Australia Market Information

ARTG Number	Product Name	Dosage Form	Approved Indication
ARTG 10272P	Kaletra	Tablet 200 mg-50 mg (oral)	Indication text not available

Safety Considerations

The following comes from knowledge-graph contraindication associations (not product label text) and from drug interaction screening.

Knowledge-graph contraindication associations (conditions linked to lopinavir):
- Cardiac and conduction: long QT syndrome (including familial), torsades de pointes, sudden cardiac arrest, heart conduction disease, atrioventricular block, cardiomyopathy (including hypertrophic), myocardial ischaemia, coronary artery disease
- Hepatic and biliary: liver disease, cirrhosis, chronic hepatitis B and C infection, gallbladder disease, hyperbilirubinaemia (including Gilbert syndrome)
- Metabolic and pancreatic: pancreatitis, hyperglycaemia, diabetes mellitus, diabetic ketoacidosis, hypertriglyceridaemia, familial combined hyperlipidaemia, potassium deficiency
- Other: haemophilia
Drug interactions (65 recorded; examples from the screening data):
- Major: dolasetron, papaverine
- Moderate: acarbose, dapagliflozin, metformin, famotidine, levofloxacin, ondansetron, palonosetron, and several laxatives (bisacodyl, castor oil, glycerin, lactitol, lactulose, magnesium citrate, magnesium hydroxide, mineral oil)
- Minor: cimetidine, clotrimazole

Product Information (PI) warnings and contraindications were not available. Please refer to the TGA-approved Product Information (PI) for authoritative safety information.

Conclusion and Next Steps

Decision: Hold

Rationale: The prediction is supported only by indirect preclinical macaque studies, and SIV infection has no human clinical indication. The other predicted indications have no supporting evidence. Lopinavir already has an established role in HIV, so this prediction offers no new therapeutic opportunity.

To proceed, the following is needed:

Confirmation that a human-relevant indication exists, since SIV and feline immunodeficiency are not human diseases
Mechanism of action data (MOA) from DrugBank
The TGA Product Information (PI), including warnings, contraindications and approved indication text
For the neurodevelopmental disorder prediction, a gene or pathway-level mechanistic link before any further consideration
Disclaimer

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