Lopinavir
| Evidence Level: L4 | Predicted Indications: 3 |
Table of Contents
Lopinavir: From HIV Infection / AIDS 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, but there are 0 clinical trials and only 3 animal-model publications supporting this direction. This is an animal-model (veterinary/research) indication rather than a human therapeutic use, and it is essentially an extension of the original antiretroviral indication.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | HIV infectious disease; AIDS (from the knowledge graph, since the New Zealand licence record has no indication text) |
| Predicted New Indication | Simian immunodeficiency virus infection |
| TxGNN Prediction Score | 99.90% |
| Evidence Level | L4 |
| New Zealand Market Status | Cancelled only (no currently valid licence) |
| Number of Authorizations | 1 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available in the data compiled for this report. Based on known information, lopinavir is an HIV-1 protease inhibitor, marketed in a fixed-dose combination with ritonavir (a pharmacokinetic booster). Its efficacy in HIV infection is established, and mechanistically it may be applicable to SIV.
SIV is a closely related primate lentivirus, and its protease is structurally similar to HIV-1 protease, so activity is biologically plausible. The available literature consists of macaque studies of combination antiretroviral regimens including lopinavir, plus a chimeric SHIV engineered with an HIV-1 protease gene so that macaques become susceptible to HIV protease inhibitors.
This evidence is indirect and preclinical. The prediction mostly reflects network proximity to the original HIV/AIDS indication, so it is not a true repurposing opportunity for a new human disease.
The other two predictions in the dataset are weaker:
- Feline acquired immunodeficiency syndrome (score 99.90%): FIV protease differs from HIV-1 protease in substrate specificity and inhibitor sensitivity, so activity cannot be assumed. No trials or literature are available (L5).
- A rare neurodevelopmental disorder with ataxic gait, absent speech and decreased cortical white matter (score 99.90%): no plausible mechanistic link was found, and the prediction is likely a graph artifact (L5).
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 16973590 | 2006 | Animal study | Journal of Virology | Four SIVmac251-infected cynomolgus macaques received 7 days of quadruple antiretroviral therapy; rapid viral decay was observed, informing comparison of viral dynamics between SIV and HIV-1 |
| 12951220 | 2003 | Animal study | Journal of Virological Methods | Two SHIV 89.6P-infected rhesus macaques received oral AZT, 3TC and lopinavir/ritonavir for 28 days; the study assessed effects on the CD8 subset |
| 17350308 | 2007 | Animal model development | Microbes and Infection | A novel SHIV carrying the HIV-1 protease gene was built; its growth was blocked by a protease inhibitor in cell culture, and it persisted weakly in macaques, making it a tool for testing protease inhibitors in vivo |
New Zealand Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| 2613549 (cancelled) | Lopinavir/Ritonavir Mylan | Tab 200 mg with ritonavir 50 mg | Not recorded |
Safety Considerations
- Contraindications / conditions of concern (from knowledge graph, not label text): long QT syndrome (including familial), torsades de pointes, sudden cardiac arrest, heart conduction disease, atrioventricular block, cardiomyopathy, myocardial ischaemia and coronary artery disease; pancreatitis; liver disease, cirrhosis, and chronic hepatitis B or C; hyperglycaemia, diabetes mellitus and diabetic ketoacidosis; hypertriglyceridaemia and familial combined hyperlipidaemia; hyperbilirubinaemia, including Gilbert syndrome; gallbladder disease; potassium deficiency; and haemophilia.
- Drug Interactions: 65 interactions recorded. Major-level interactions include dolasetron and papaverine. Moderate-level interactions include acarbose, dapagliflozin, metformin, famotidine, levofloxacin and ondansetron, among others. Minor-level interactions include cimetidine and clotrimazole.
Package insert warnings and contraindications were not available, so please refer to the package insert for full safety information.
Conclusion and Next Steps
Decision: Hold
Rationale: The only supporting evidence is three preclinical macaque studies, with no registered clinical trials. SIV infection is an animal-model indication rather than a human therapeutic use, so the prediction extends the original antiretroviral indication rather than opening a new treatment opportunity. The product's only New Zealand licence is cancelled.
To proceed, the following is needed:
- Medsafe package insert warnings and contraindications (a blocking gap for safety screening)
- Mechanism of action data from DrugBank
- Clarification of whether a research or veterinary use case justifies further work
- If a human indication is pursued instead, new mechanistic work and a safety review given the cardiac, hepatic, metabolic and interaction concerns listed above
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.