Raltegravir
| Evidence Level: L4 | Predicted Indications: 10 |
Table of Contents
Raltegravir: From HIV-1 Infection to Simian Immunodeficiency Virus (SIV) Infection
One-Sentence Summary
Raltegravir is an HIV-1 integrase strand transfer inhibitor; its established indication is HIV-1 infection, though this evidence pack contains no formal licensing/MOA data confirming this (both flagged as data gaps). The TxGNN model’s top-ranked prediction is Simian Immunodeficiency Virus (SIV) Infection, which the evidence pack’s own analysis flags as a species/entity-mapping artifact rather than a translatable human indication — it is supported by only 1 withdrawn clinical trial (zero enrollment) and 19 mostly preclinical/animal-model publications.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not available — drug is not currently marketed/licensed in this jurisdiction (no license records); publicly known indication is HIV-1 infection |
| Predicted New Indication | Simian Immunodeficiency Virus (SIV) Infection |
| TxGNN Prediction Score | 99.78% |
| 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 (flagged as a data gap, DG002). Based on known public drug information, Raltegravir is an HIV-1 integrase strand transfer inhibitor, and its efficacy in HIV-1 infection is well established in clinical practice.
SIV is a primate lentivirus that shares the same genus (Lentivirus) as HIV and a homologous integrase domain, so the drug’s integrase-inhibition mechanism is plausible in nonhuman primate models — several preclinical studies in this pack do use raltegravir-based ART in SIV-infected rhesus macaques as a research tool. However, SIV infection is a veterinary/research-model disease, not a human disease, and does not constitute a clinically translatable repurposing indication. This top-ranked prediction most likely reflects a knowledge-graph entity mapping artifact (HIV/SIV structural similarity in the graph) rather than a genuine repurposing opportunity.
Notably, two lower-ranked but far more clinically credible signals exist further down this evidence pack: congenital HIV infection (rank 4, L2, “Proceed with Guardrails”) and AIDS related complex (rank 5, L2, “Proceed with Guardrails”). Both represent legitimate extensions of raltegravir’s existing HIV indication into specific populations (neonatal/pregnancy PMTCT, pediatric use) and disease staging, backed by real Phase 1–4 trials and cohort/pharmacovigilance literature — unlike the SIV prediction, these are not novel repurposing hypotheses but confirmatory extensions of known use, and may warrant a separate evaluation as their own candidates.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT00863668 | NA | Withdrawn | 0 | Intended to study HIV/SIV viral decay kinetics under integrase-inhibitor ART; trial was withdrawn with zero enrollment, yielding no usable data. |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 20233398 | 2010 | Preclinical (animal model) | Retrovirology | Established a raltegravir-based ART regimen in SIVmac251-infected macaques, creating an animal model for lentiviral persistence research. |
| 32166319 | 2020 | Preclinical (mechanistic) | Clin Infect Dis | Raltegravir and dolutegravir shown to exert proadipogenic/profibrotic effects and induce insulin resistance in human/simian adipose tissue models. |
| 26378179 | 2015 | Preclinical (animal model) | J Virol | Characterized integrase strand-transfer inhibitor resistance mutation profiles in SIVmac239. |
| 24622515 | 2014 | Preclinical (animal model, PrEP) | Sci Transl Med | Topical integrase inhibitors tested for postexposure protection against vaginal SHIV infection in macaques. |
| 28923862 | 2017 | Preclinical (in vitro/animal) | Antimicrob Agents Chemother | Evaluated antiviral activity of newer integrase inhibitors against raltegravir-resistant SIVmac239 and HIV-1. |
| 29643246 | 2018 | Preclinical (animal model) | J Virol | Assessed 2-LTR circle dynamics in raltegravir-treated, SIV-infected macaques to study CD8+ cell-mediated viral control. |
| 29466356 | 2018 | Preclinical (animal model) | PLoS One | Documented emergence of resistance mutations in SIV-infected macaques receiving raltegravir-intensified non-suppressive ART. |
| 31597776 | 2019 | Preclinical (animal model) | J Virol | Evaluated persistence of intact viral genomes in SIV-infected macaques after early raltegravir-based ART initiation. |
| 34903055 | 2021 | Preclinical (animal model) | mBio | Investigated CNS lentiviral persistence despite effective ART (including raltegravir) in SIV brain infection models. |
| 23365453 | 2013 | Preclinical (in vitro) | J Virol | In vitro susceptibility analysis of simian retrovirus type 4 to antiretroviral agents including raltegravir. |
EU Market Information
Raltegravir currently has no marketing authorization on record in this dataset (market status: not marketed, 0 licenses). No product/authorization table is available.
Safety Considerations
Please refer to the SmPC for safety information. (Key warnings, contraindications, and drug-drug interaction data are all marked as data gaps in this evidence pack — TFDA/regulatory label warnings are flagged as a Blocking data gap, DG001.)
Conclusion and Next Steps
Decision: Hold
Rationale: The top-ranked prediction, SIV infection, is not a human disease and does not constitute a clinically actionable repurposing candidate — the evidence pack’s own rationale identifies it as a likely entity-mapping artifact from HIV/SIV mechanistic homology. Supporting evidence is limited to one withdrawn trial (zero enrollment) and preclinical animal-model literature (L4), insufficient to justify progression.
To proceed, the following is needed:
- Resolve the Blocking data gap (DG001): retrieve official label warnings/contraindications before any safety pre-screening (S1) can occur
- Resolve the mechanism-of-action data gap (DG002) via DrugBank API
- If pursuing repurposing signals from this pack, redirect evaluation toward the human-relevant candidates — congenital HIV infection and AIDS related complex (both L2, “Proceed with Guardrails”) — as separate, better-supported candidates rather than the SIV signal
- Confirm/obtain formal original-indication licensing text, since no EU authorization record currently exists for this drug in this dataset
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.