Elvitegravir
| Evidence Level: L5 | Predicted Indications: 3 |
Table of Contents
- Elvitegravir
- Pharmacist Assessment Report
- Elvitegravir: From HIV Infection to Feline Acquired Immunodeficiency Syndrome
- One-Sentence Summary
- Quick Overview
- Why is This Prediction Reasonable?
- Clinical Trial Evidence
- Literature Evidence
- Canada Market Information
- Safety Considerations
- Conclusion and Next Steps
- Disclaimer
Elvitegravir: From HIV Infection to Feline Acquired Immunodeficiency Syndrome
One-Sentence Summary
Elvitegravir is an HIV integrase inhibitor, originally used to treat HIV infection and AIDS. The TxGNN model’s top-ranked prediction is feline acquired immunodeficiency syndrome, which has no supporting studies. The best-supported direction is simian immunodeficiency virus (SIV) infection, with 0 clinical trials and 8 preclinical publications currently supporting it.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | HIV infection, AIDS (the Canadian licence records contain no indication text) |
| Predicted New Indication | Feline acquired immunodeficiency syndrome (rank 1, no evidence); the best-supported prediction is SIV infection (rank 2) |
| TxGNN Prediction Score | 0.9989 (both feline AIDS and SIV infection) |
| Evidence Level | L5 for feline AIDS; L4 for SIV infection |
| Canada Market Status | Marketed (marketed DINs: 2 of 2) |
| Number of DINs | 2 (marketed: 2) |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not currently available in the data compiled for this report. Based on known information, elvitegravir is an HIV-1 integrase strand transfer inhibitor. It blocks the step in which viral DNA is inserted into the host genome, and its efficacy in HIV infection is established.
Feline AIDS (rank 1). The feline immunodeficiency virus (FIV) is a lentivirus related to HIV-1 and also encodes an integrase enzyme, so activity is biologically plausible. However, there are no trials, no literature, and no laboratory data on FIV. The high score is a computational prediction from the TxGNN model (deep learning) and may reflect similarities the model learned between related diseases, such as the disease’s similarity to HIV/AIDS, not biological evidence. Differences between the FIV and HIV-1 integrase sequences could reduce susceptibility, and this has not been tested.
SIV infection (rank 2). SIV and HIV-1 integrases are closely related, and the preclinical literature shows that SIVmac239 is susceptible to integrase inhibitors and develops similar resistance mutations. Macaque studies of topical tenofovir alafenamide/elvitegravir inserts showed protection against SHIV (a simian/human hybrid virus). SIV infection is not a human clinical indication, so its realistic value is as a preclinical model for HIV prevention and treatment, which overlaps with elvitegravir’s existing indication. The one prophylaxis study with elvitegravir in the rectal model showed only partial protection.
Neurodevelopmental disorder (rank 3). The third prediction, a neurodevelopmental disorder with ataxic gait, absent speech, and decreased cortical white matter, has no evident mechanistic link. Elvitegravir targets a viral enzyme with no relevant human counterpart, and its brain penetration is limited. This prediction is likely a network artifact and is not evaluated further.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
The following publications relate to SIV infection (rank 2). All are preclinical; no literature was found for the other two predictions.
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 38134382 | 2024 | Preclinical (macaque challenge) | J Infect Dis | Vaginal TAF/elvitegravir inserts gave extended post-exposure protection against SHIV in macaques; earlier work showed 93% (before exposure) and 100% (after exposure) protection |
| 41342257 | 2026 | Preclinical (macaque challenge) | J Infect Dis | Rectal TAF/elvitegravir inserts gave partial post-exposure protection against SHIV (82.9%); 93% efficacy as pre-exposure prophylaxis |
| 39559349 | 2024 | Preclinical (humanized mouse) | Front Immunol | Dual-purpose humanized mouse model for testing antiviral strategies against both SIV and HIV |
| 17977962 | 2008 | Preclinical (in vitro) | J Virol | Elvitegravir blocks HIV-1 integration by inhibiting DNA strand transfer; broad activity across subtypes and drug-resistant strains, with a resistance profile described |
| 25583721 | 2015 | Preclinical (in vitro) | Antimicrob Agents Chemother | Simian-tropic HIV as a model for studying resistance to integrase inhibitors |
| 24920794 | 2014 | Preclinical (in vitro) | J Virol | HIV integrase resistance mutations introduced into SIVmac239 and their effect on integrase inhibitor susceptibility |
| 26378179 | 2015 | Preclinical (in vitro) | J Virol | Resistance profiles of integrase inhibitors in SIVmac239; SIV is susceptible and shows resistance phenotypes similar to HIV |
| 28923862 | 2017 | Preclinical (in vitro) | Antimicrob Agents Chemother | Bictegravir and cabotegravir activity against integrase inhibitor-resistant SIVmac239 and HIV-1 |
Canada Market Information
| DIN | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| 02449498 | GENVOYA | Not specified | Not specified |
| 02397137 | STRIBILD | Not specified | Not specified |
Safety Considerations
Drug Interactions: 27 interactions were identified in total. The major-level interactions among those listed are:
- Zinc acetate, zinc gluconate, zinc sulfate, and zinc chloride
- Lumacaftor
- Apalutamide
Moderate-level interactions include:
- Antacids and mineral supplements (magnesium oxide, magnesium hydroxide, magnesium carbonate, magaldrate, aluminum hydroxide, calcium carbonate, sodium citrate, sodium bicarbonate), which may reduce absorption
- Dexamethasone, orlistat, diclofenac, elagolix, somatotropin, and ethinylestradiol
Please refer to the package insert for warnings and contraindications.
Conclusion and Next Steps
Decision: Hold
Rationale: The top-ranked prediction (feline AIDS) rests on a model score alone, and the neurodevelopmental disorder prediction has no plausible mechanism. The SIV evidence is preclinical, indirect, and shows only partial protection in one study. SIV infection is not a human indication, so its value is as a research model for HIV rather than a new treatment, and it overlaps with elvitegravir’s existing approved use.
To proceed, the following is needed:
- Package insert warnings and contraindications from Health Canada
- Detailed mechanism of action data (MOA)
- For feline AIDS: laboratory data on elvitegravir activity against FIV integrase
- For SIV: a defined research purpose, such as use as a model for HIV prevention, rather than a therapeutic indication
- Indication text and dosage forms for the two Canadian authorisations (GENVOYA and STRIBILD)
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.