Lopinavir
| Evidence Level: L4 | Predicted Indications: 10 |
Table of Contents
Lopinavir: From HIV-1 Infection to Simian Immunodeficiency Virus Infection
One-Sentence Summary
Lopinavir (co-formulated with ritonavir as Lopinavir/Ritonavir, brand name Kaletra) is an HIV-1 protease inhibitor originally used for HIV-1 infection. The TxGNN model’s top-ranked prediction suggests it may be effective for Simian Immunodeficiency Virus (SIV) Infection, but this is currently supported by 0 clinical trials and only 3 publications (all animal-model studies), placing it at the lowest evidence tier.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | HIV-1 Infection (established antiretroviral use, as part of Lopinavir/Ritonavir combination therapy) |
| Predicted New Indication | Simian Immunodeficiency Virus (SIV) Infection |
| TxGNN Prediction Score | 99.90% |
| Evidence Level | L4 |
| EU Market Status | Not marketed |
| Number of Authorizations | 0 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available from DrugBank for this evidence pack. Based on well-established pharmacology, Lopinavir is a HIV-1 protease inhibitor, boosted by ritonavir (Lopinavir/Ritonavir, Kaletra), and its efficacy in HIV-1 infection has been extensively proven in clinical practice.
The predicted new indication, SIV infection, is a lentivirus disease affecting non-human primates. SIV protease shares high structural homology with HIV-1 protease, which is why SIV-infected macaque models have long served as a preclinical platform to test antiretroviral regimens intended for human HIV-1 treatment.
However, this prediction is essentially a veterinary/animal-model application rather than a genuine human clinical indication. The high TxGNN score (99.90%) likely reflects tight embedding-space proximity between “SIV” and “HIV” nodes in the knowledge graph, rather than an unmet human therapeutic need. It should be read as a technical extension of the existing HIV-1 indication, not a novel repurposing opportunity for human patients.
Note: Within the same evidence pack, two other predicted indications — congenital human immunodeficiency virus (rank 4) and AIDS related complex (rank 5) — carry L1 evidence (multiple completed Phase 3 RCTs, “Proceed with Guardrails”). These are stronger, clinically meaningful signals but represent extensions of the already-approved HIV-1 indication rather than the model’s top-ranked (rank 1) prediction reported above.
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 antiretroviral therapy produced rapid viral decay in SIV-infected cynomolgus macaques |
| 17350308 | 2007 | Animal Study (SHIV construct) | Microbes and Infection | Novel SHIV bearing an HIV-1-derived protease gene, used as an in vivo platform for testing protease inhibitors |
| 12951220 | 2003 | Animal Study (Macaque) | Journal of Virological Methods | Oral HAART including Lopinavir/Ritonavir affected CD8 subset in SHIV-infected monkeys |
EU Market Information
Lopinavir currently holds no EU marketing authorizations on record (market status: not marketed, 0 licenses).
Safety Considerations
Please refer to the SmPC for safety information.
(Note: TFDA/EMA label warnings and contraindications are flagged as a Blocking data gap — DG001 — pending SmPC PDF retrieval and parsing.)
Conclusion and Next Steps
Decision: Hold
Rationale: The top-ranked prediction (SIV infection) has no clinical trial support and is backed only by three Tier-3 animal-model publications. It represents a veterinary/preclinical model condition rather than a human therapeutic need, and the high TxGNN score is best explained by knowledge-graph node proximity (SIV↔HIV) rather than a genuine repurposing signal.
To proceed, the following is needed:
- Confirm this candidate should not advance as a human indication; redirect evaluation focus to the higher-evidence candidates in this same evidence pack (congenital HIV infection and AIDS related complex, both L1 / Proceed with Guardrails)
- Resolve DG001 (TFDA/EMA label warnings and contraindications — Blocking)
- Resolve DG002 (detailed mechanism of action from DrugBank)
- Verify EU marketing authorization status, since current data shows 0 licenses
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.