Dolutegravir
| Evidence Level: L5 | Predicted Indications: 3 |
Table of Contents
- Dolutegravir
- Pharmacist Assessment Report
- Dolutegravir: 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
Dolutegravir: From HIV Infection to Feline Acquired Immunodeficiency Syndrome
One-Sentence Summary
Dolutegravir is an HIV-1 integrase inhibitor originally used to treat HIV infection and AIDS. The TxGNN model predicts it may be effective for feline acquired immunodeficiency syndrome (FIV), but there are 0 registered clinical trials and only 1 publication (a veterinary preclinical study) supporting this direction.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | HIV infectious disease; AIDS |
| Predicted New Indication | Feline acquired immunodeficiency syndrome |
| TxGNN Prediction Score | 0.9985 |
| Evidence Level | L5 |
| Canada Market Status | Marketed (marketed DINs: 5 of 5) |
| Number of DINs | 5 (marketed: 5) |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Dolutegravir is an HIV-1 integrase strand transfer inhibitor. It blocks the viral enzyme that inserts viral DNA into the host genome, a step required for the virus to replicate. Detailed mechanism of action data is not available in the data compiled for this report, so this description is based on the drug’s known class.
Feline immunodeficiency virus (FIV) is a lentivirus that causes progressive immune dysfunction in cats, much like HIV does in humans. Its integrase enzyme is structurally related to that of HIV, so a mechanistic rationale exists for the prediction.
The very high TxGNN score reflects a network-based prediction, not clinical validation. The only supporting study is a 2023 preclinical report of a combination regimen (dolutegravir, tenofovir, emtricitabine) in FIV-infected cats, so dolutegravir’s individual contribution is unclear. Because this is a veterinary indication and dolutegravir is already marketed for HIV, the repurposing value for human medicine is limited.
Two other predictions were also generated, but they are weaker or of limited relevance:
- Simian immunodeficiency virus infection (score 0.9985): Evidence is animal and preclinical only, including dolutegravir monotherapy in SIV-infected macaques. SIV is mainly a research model for HIV, not a new human indication.
- A rare neurodevelopmental disorder with ataxic gait, absent speech, and decreased cortical white matter (score 0.9980): No mechanistic link, trials or literature were found. This is likely a TxGNN model (deep learning) artifact.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 37112803 | 2023 | Preclinical/Veterinary study | Viruses | Evaluated pharmacokinetics and clinical outcomes of combination antiretroviral therapy (dolutegravir, tenofovir, emtricitabine) in FIV-infected domestic cats, along with immunophenotype. |
For reference, the related SIV prediction has more preclinical literature, for example 30381490 (2019, J Virol), which describes dolutegravir monotherapy in SIV-infected macaques selecting for several resistance mutation patterns with variable virological outcomes.
Canada Market Information
| DIN | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| 02511517 | TIVICAY | Not specified | Not specified |
| 02414945 | TIVICAY | Not specified | Not specified |
| 02491753 | DOVATO | Not specified | Not specified |
| 02475774 | JULUCA | Not specified | Not specified |
| 02430932 | TRIUMEQ | Not specified | Not specified |
Safety Considerations
- Drug Interactions: 62 interactions were identified. Major interactions are mainly with polyvalent cation products, which can reduce dolutegravir absorption by chelation:
- Antacids and minerals: aluminum hydroxide, magaldrate, magnesium carbonate, magnesium chloride, magnesium citrate
- Calcium salts: calcium acetate, calcium carbonate, calcium citrate, calcium glubionate, calcium gluconate, calcium lactate, calcium phosphate
- Others: iron, kaolin, attapulgite
- Minor interactions include aprepitant, cimetidine, clarithromycin, clotrimazole and dexamethasone.
- Neural tube defect and neuropsychiatric adverse event considerations are relevant to dolutegravir, particularly in any neurodevelopmental context.
Please refer to the package insert for warnings and contraindications.
Conclusion and Next Steps
Decision: Hold
Rationale: The prediction is supported by only one veterinary preclinical study of a combination regimen and no clinical trials. The predicted indication is a veterinary disease, and dolutegravir is already marketed for HIV, so the value as a human repurposing candidate is limited.
To proceed, the following is needed:
- Health Canada package insert warnings and contraindications, which are required before safety screening
- Detailed mechanism of action data
- Dolutegravir-specific efficacy and pharmacokinetic data in FIV-infected cats (separate from the combination regimen)
- A decision on whether a veterinary indication falls within the scope of this repurposing program
- Target and pathway analysis for the neurodevelopmental disorder prediction, if it is to be pursued at all
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.