Raltegravir
| Evidence Level: L4 | Predicted Indications: 3 |
Table of Contents
Raltegravir: From HIV-1 Infection to Simian Immunodeficiency Virus Infection
One-Sentence Summary
Raltegravir is an HIV-1 integrase strand transfer inhibitor (INSTI) with an established antiretroviral profile, but it is not currently marketed in Taiwan and detailed original-indication/MOA data are missing from this evidence pack. The TxGNN model’s top prediction — Simian Immunodeficiency Virus (SIV) Infection — is not a human clinical indication; it is an animal-model disease used in HIV translational research, and the single linked clinical trial is a mismatched pairing artifact. Evidence level is L4 (mechanistic/preclinical only), supported by 1 loosely related clinical trial and ~20 preclinical/animal publications, none of which establish a human therapeutic use.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not documented in evidence pack (data gap); Raltegravir is clinically known as an HIV-1 integrase inhibitor |
| Predicted New Indication | Simian Immunodeficiency Virus (SIV) Infection |
| TxGNN Prediction Score | 99.78% |
| Evidence Level | L4 |
| Taiwan Market Status | Not Marketed (Not marketed) |
| Number of Registrations | 0 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available (DG002, High severity). Based on known pharmacology, Raltegravir is an HIV-1 integrase strand transfer inhibitor (INSTI), and its efficacy in HIV-1 infection is well established in clinical practice, even though the formal Taiwan-approved indication text is not present in this dataset (drug is currently not marketed in Taiwan, 0 registrations).
The mechanistic rationale for the predicted indication rests on viral homology rather than a distinct human disease target: SIV and HIV are both lentiviruses with highly conserved integrase structures, so INSTIs like raltegravir are pharmacologically active against SIV in vitro and in nonhuman primate models. However, SIV infection is a disease of nonhuman primates (e.g., rhesus macaques), not a human condition — it is used almost exclusively as a translational research model to study HIV pathophysiology, viral reservoirs, and antiretroviral pharmacodynamics, not as a target for new human drug indications.
The single clinical trial linked to this prediction (NCT00863668) was itself a human HIV decay-kinetics study, was withdrawn (enrollment = 0), and was flagged by the source evidence pack as a mismatched pairing (“Grade C” relevance — disease label does not match trial content). All supporting literature consists of tier-3 animal/in-vitro studies. Taken together, this prediction should be interpreted as a knowledge-graph artifact driven by semantic/ontological proximity between “HIV” and “SIV,” rather than a genuine actionable repurposing signal. (The pack’s own two lower-ranked predictions — feline AIDS and a rare pediatric neurodevelopmental disorder — show the same pattern: no credible mechanistic or clinical link, evidence level L5, recommendation Hold.)
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT00863668 | NA | Withdrawn | 0 | Study of HIV (not SIV) viral decay kinetics under raltegravir-based ART; withdrawn with zero enrollment. Flagged as a disease-label mismatch (Grade C) — not genuine SIV evidence. |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 20233398 | 2010 | Animal model (SIVmac251 macaque) | Retrovirology | Raltegravir-based ART regimen tested in SIVmac251-infected macaques as a model for lentiviral persistence during therapy |
| 29643246 | 2018 | Animal study (viral dynamics) | Journal of Virology | 2-LTR circle dynamics in raltegravir-treated SIV-infected macaques with/without CD8+ cells |
| 31597776 | 2019 | Animal study (viral genomics) | Journal of Virology | Intactness of persistent SIV genomes in macaques after early ART initiation |
| 32166319 | 2020 | Animal/cell study (metabolic toxicity) | Clin Infect Dis | Raltegravir and dolutegravir show proadipogenic/profibrotic effects and insulin resistance in adipose tissue |
| 29466356 | 2018 | Animal study (resistance) | PLoS One | Resistance mutations emerge in SIV-infected macaques on non-suppressive raltegravir-containing ART |
| 26378179 | 2015 | Animal/resistance profiling | Journal of Virology | Drug resistance profiles of integrase inhibitors characterized in SIVmac239 |
| 24622515 | 2014 | Animal study (prevention) | Science Translational Medicine | Topical integrase inhibitors for post-exposure protection against vaginal SHIV infection in macaques |
| 34903055 | 2021 | Animal/neuroimmune study | mBio | Lentiviral persistence in brain despite effective ART in animal/human tissue models |
| 28923862 | 2017 | In vitro/animal antiviral activity | Antimicrob Agents Chemother | Bictegravir/cabotegravir activity against integrase-inhibitor-resistant SIVmac239 and HIV-1 (raltegravir comparator) |
| 23365453 | 2013 | In vitro susceptibility | Journal of Virology | Susceptibility of simian retrovirus type 4 to antiretrovirals including raltegravir |
Taiwan Market Information
Raltegravir is currently not marketed in Taiwan (0 registered licenses). No product registration, dosage form, or approved-indication text is available in this evidence pack.
Safety Considerations
Drug Interactions (from DDI database, 36 total interactions identified; key clinically relevant ones below):
| Interacting Drug | Severity |
|---|---|
| Aluminum hydroxide | Major |
| Calcium carbonate | Major |
| Zinc sulfate | Major |
| Zinc acetate | Major |
| Magnesium oxide | Moderate |
| Magnesium sulfate | Moderate |
| Magnesium chloride | Moderate |
| Orlistat | Moderate |
| Omeprazole, Esomeprazole, Pantoprazole, Lansoprazole, Dexlansoprazole, Rabeprazole (PPIs) | Minor |
| Famotidine, Ranitidine, Cimetidine, Nizatidine (H2 blockers) | Minor |
| Pioglitazone, Dexamethasone | Minor |
The Major-severity pattern (polyvalent cation antacids/minerals — Al, Ca, Zn, Mg) is consistent with raltegravir’s known chelation-mediated absorption reduction and should be treated as clinically significant even though formal Taiwan label warnings and contraindications are not available in this dataset (data gap DG001, Blocking severity).
Conclusion and Next Steps
Decision: Hold
Rationale: The top-ranked TxGNN prediction (SIV infection) targets a nonhuman-primate disease with no human clinical relevance; its only linked clinical trial is a confirmed disease-label mismatch, and all literature is preclinical/animal-model research (Evidence Level L4). The two next-ranked predictions (feline AIDS, a rare pediatric neurodevelopmental disorder) are even weaker (L5, no trials, no literature) and represent likely knowledge-graph artifacts rather than actionable signals.
To proceed, the following is needed:
- TFDA label warnings/contraindications (DG001, Blocking) before any safety evaluation (S1) can begin
- Confirmed mechanism of action from DrugBank (DG002)
- Re-run TxGNN disease-candidate review with non-human/veterinary and ultra-rare monogenic disease categories filtered out, to surface genuinely actionable human indications further down the ranked list
- If a human-relevant indication is identified in later ranks, re-evaluate market entry strategy given raltegravir’s current non-marketed status in Taiwan
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.