Elvitegravir

證據等級: L5

預測適應症: 3 個

Elvitegravir: From HIV-1 Infection to Simian Immunodeficiency Virus (SIV) Infection (Preclinical Model)

One-Sentence Summary

Elvitegravir is an HIV-1 integrase strand transfer inhibitor (INSTI), originally developed as a component of combination antiretroviral therapy for HIV-1 infection. The TxGNN model predicts activity relevant to Simian Immunodeficiency Virus (SIV) infection — a lentivirus closely related to HIV-1 used in non-human primate research models — with 0 clinical trials and 7 preclinical publications currently supporting this direction. Two additional low-confidence predictions (feline AIDS and an unrelated rare neurodevelopmental disorder) were also generated by TxGNN but carry no supporting evidence and are addressed separately below.

Quick Overview

Item	Content
Original Indication	Not formally recorded in the source dataset (`original_indications` is empty and `original_moa` is a data gap). Based on the evidence pack's own mechanistic description, elvitegravir is an HIV-1 integrase strand transfer inhibitor used as part of combination antiretroviral therapy for HIV-1 infection.
Predicted New Indication	Simian Immunodeficiency Virus (SIV) Infection (a non-human primate lentivirus model, not a human clinical indication)
TxGNN Prediction Score	99.89%
Evidence Level	L3 (per pipeline scoring; note all supporting literature is preclinical/animal-model — see caveat below)
Finland Market Status	未上市 (Not Marketed)
Number of Authorizations	0
Recommended Decision	Hold

Note on the other two TxGNN predictions in this pack:

Rank	Predicted Indication	TxGNN Score	Evidence	Decision
1	Feline acquired immunodeficiency syndrome (FIV)	99.89%	0 trials, 0 literature	Hold
3	Neurodevelopmental disorder with ataxic gait, absent speech, and decreased cortical white matter	99.87%	0 trials, 0 literature	Hold — likely false-positive knowledge-graph association

Why is This Prediction Reasonable?

Detailed, formally sourced mechanism-of-action data (DrugBank original_moa field) is currently marked as a data gap in this evidence pack. However, based on the mechanistic description embedded in the TxGNN rationale, elvitegravir is known to act as an HIV-1 integrase strand transfer inhibitor (INSTI), blocking the strand-transfer step of viral cDNA integration into the host genome. It is developed and marketed as a component of fixed-dose combination antiretroviral regimens (e.g., alongside cobicistat, emtricitabine, and tenofovir) for HIV-1 infection in humans.

SIV (simian immunodeficiency virus) is a lentivirus closely related to HIV-1, and SIV/SHIV-infected macaque models are the standard non-human-primate platform used throughout antiretroviral drug development — including for resistance profiling and pre-exposure/post-exposure prophylaxis studies. Because HIV-1 and SIV integrase share substantial structural and functional homology, INSTIs developed against HIV-1 — including elvitegravir itself — have been directly tested and shown to retain antiviral activity against SIV in vitro and in animal models.

Importantly, this predicted "indication" is not a new human disease target in the traditional repurposing sense — it reflects elvitegravir's established role as a research/reference compound in the SIV/SHIV non-human-primate model system rather than a novel clinical population. This distinguishes it from the typical drug-repurposing scenario (e.g., a cardiovascular drug repurposed for cancer) and should be interpreted as validating the model's biological plausibility (correctly identifying an HIV-1 ↔ SIV mechanistic link) rather than surfacing a new therapeutic opportunity requiring clinical development.

Clinical Trial Evidence

Currently no related clinical trials registered.

Literature Evidence

PMID	Year	Type	Journal	Key Findings
17977962	2008	Preclinical (in vitro characterization)	Journal of Virology	Original characterization of elvitegravir (JTK-303/GS-9137): blocks HIV-1 cDNA integration via strand-transfer inhibition; active against multiple HIV-1 subtypes and drug-resistant isolates.
26378179	2015	Preclinical (resistance profiling, SIV model)	Journal of Virology	Confirms SIVmac239 is susceptible to HIV-1 integrase strand transfer inhibitors (INSTIs), with resistance mutations producing similar phenotypes in both viruses.
24920794	2014	Preclinical (resistance mutation study)	Journal of Virology	HIV-1 integrase resistance mutations (including those selected under elvitegravir pressure) introduced into SIVmac239 alter susceptibility to INSTIs, supporting cross-species mechanistic relevance.
25583721	2015	Preclinical (animal model methodology)	Antimicrobial Agents and Chemotherapy	Establishes simian-tropic HIV as a model for studying INSTI drug resistance, building on SIV/HIV integrase homology.
39559349	2024	Preclinical (humanized mouse model)	Frontiers in Immunology	Describes a dual-purpose humanized mouse model for testing antiviral strategies against both SIV and HIV.
38134382	2024	Preclinical (postexposure prophylaxis, not elvitegravir-specific alone)	The Journal of Infectious Diseases	Tenofovir alafenamide/elvitegravir vaginal inserts show extended postexposure protection against SHIV in macaques (93–100% protection).
28923862	2017	Preclinical (class-analog antiviral activity)	Antimicrobial Agents and Chemotherapy	Evaluates bictegravir/cabotegravir (later-generation INSTIs) against integrase-inhibitor-resistant SIVmac239 and HIV-1; references elvitegravir as a comparator/predecessor compound.

Caveat: all seven publications are preclinical (in vitro, cell-based, or non-human-primate/mouse model) studies. Only two (PMID 17977962, 38134382) test elvitegravir directly; the remainder study SIV/INSTI-class biology or later-generation analogs. No human clinical data exist for this application.

Finland Market Information

Elvitegravir currently has no marketing authorizations in Finland (0 authorizations registered; market status: 未上市/Not Marketed).

Safety Considerations

Please refer to the package insert for safety information.

(All safety fields in the source evidence pack — key warnings, contraindications, and drug-drug interactions — are marked as data gaps. Notably, DG001 flags TFDA package-insert warnings/contraindications as a Blocking data gap, meaning this candidate cannot yet proceed to a formal S1 safety review.)

Conclusion and Next Steps

Decision: Hold

Rationale: The TxGNN signal for SIV infection is mechanistically plausible and supported by seven preclinical publications, but it reflects elvitegravir's known role in a non-human-primate research model rather than a validated new human clinical indication — no clinical trials exist, and the drug is not currently marketed in Finland. Combined with a blocking data gap in TFDA safety/label information (DG001), this candidate cannot proceed past preliminary research review. The other two TxGNN predictions in this pack (feline AIDS, and the unrelated neurodevelopmental disorder) have no supporting evidence at all and should remain on hold; the neurodevelopmental disorder prediction in particular should be treated as a likely knowledge-graph false positive given the absence of any plausible mechanistic link.

To proceed, the following is needed:

TFDA/regulatory package insert with warnings, contraindications, and DDI data (currently Blocking gap DG001)
Formal DrugBank-sourced mechanism-of-action (MOA) record (currently High-severity gap DG002)
Clarification of translational relevance: since SIV infection is an animal-model construct, define what human clinical population (if any) this signal is meant to support before further evidence collection
If pursuing the feline AIDS (FIV) signal as a veterinary application, commission dedicated in vitro/in vivo FIV-integrase inhibition studies, since no such data currently exist
No further action recommended on the neurodevelopmental disorder prediction absent a demonstrable mechanistic rationale
Disclaimer

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