Atazanavir
| Evidence Level: L4 | Predicted Indications: 4 |
Table of Contents
- Atazanavir
- Pharmacist Assessment Report
- Atazanavir: From HIV Infection to Simian Immunodeficiency Virus Infection
- 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
Atazanavir: From HIV Infection to Simian Immunodeficiency Virus Infection
One-Sentence Summary
Atazanavir is an HIV-1 protease inhibitor, originally used to treat HIV infection and AIDS. The TxGNN model predicts it may be effective for simian immunodeficiency virus (SIV) infection, but there are no registered clinical trials and only 1 publication (a non-human primate study) behind this prediction. In practice, this is an extension of the original indication to an animal-model virus rather than a true repurposing opportunity.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | HIV infectious disease; AIDS (approved indication text is not available in the Canadian licence records) |
| Predicted New Indication | Simian immunodeficiency virus infection |
| TxGNN Prediction Score | 0.9998 |
| Evidence Level | L4 |
| Canada Market Status | Marketed (marketed DINs: 6 of 11; dormant: 3; cancelled: 2) |
| Number of DINs | 11 (marketed: 6) |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available in the data compiled for this report. Based on known information, atazanavir is an HIV-1 protease inhibitor. Its efficacy in HIV infection is established, and mechanistically it may be applicable to related lentiviruses.
SIV is the macaque lentiviral counterpart of HIV-1, so protease inhibition is biologically plausible. The high TxGNN score comes from the TxGNN model (deep learning) and may reflect similarities the model learned between related diseases, not biological evidence. This is essentially the original indication carried over to an animal-model virus, and it does not represent a new human therapeutic area.
The other predictions are weaker or less relevant:
- Feline acquired immunodeficiency syndrome (score 0.9998): a veterinary lentiviral condition with no trials or literature. Protease inhibition is theoretically plausible, but there is no supporting evidence.
- A rare neurodevelopmental disorder (score 0.9998): no mechanistic link was identified, and the score is probably a TxGNN model (deep learning) artifact.
- Obsolete familial combined hyperlipidemia (score 0.9982): protease inhibitors are generally associated with adverse lipid effects, so a benefit is not supported.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 20497048 | 2010 | Animal study (non-human primate) | The Journal of Infectious Diseases | In SIV-infected macaques given highly active antiretroviral therapy, central nervous system viral replication and inflammation were reduced, but viral DNA persisted. |
Canada Market Information
| DIN | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| 02248611 | REYATAZ | Not specified | Not specified |
| 02294176 | REYATAZ | Not specified | Not specified |
| 02513102 | JAMP ATAZANAVIR | Not specified | Not specified |
| 02456893 | MYLAN-ATAZANAVIR | Not specified | Not specified |
| 02443821 | TEVA-ATAZANAVIR | Not specified | Not specified |
The table shows the first five.
Safety Considerations
Contraindication-related conditions (from the knowledge graph, not label text): liver failure, liver disease, gallbladder disease, hyperglycemia, diabetes mellitus, diabetic ketoacidosis, chronic hepatitis B and C virus infection, hemophilia, hyperbilirubinemia (including hereditary forms and Gilbert syndrome), nephrolithiasis, acute urate nephropathy, atrioventricular block, and lactic acidosis.
Drug Interactions: 100 interactions were found in total. Examples of major interactions include:
- Acid-suppressing drugs: famotidine, ranitidine, rabeprazole, omeprazole
- Corticosteroids: triamcinolone, budesonide
- Loperamide
Examples of moderate interactions include:
- Antidiabetic drugs: acarbose, alogliptin, metformin, pioglitazone, albiglutide, acetohexamide
- Others: hydrocortisone, betamethasone, alosetron, aprepitant, aluminum hydroxide, calcium carbonate
Package insert warnings and contraindications were not available in the data compiled for this report. Please refer to the package insert for full safety information.
Conclusion and Next Steps
Decision: Hold
Rationale: The top predictions are either the original HIV indication extended to animal viruses (SIV, feline AIDS) or are unsupported by mechanism. Evidence is limited to a single non-human primate study, with no human trials, so there is no actionable repurposing opportunity at present. Of the predictions, congenital HIV has the most literature (L3), but it is a population extension of the existing HIV indication.
To proceed, the following is needed:
- Health Canada package insert warnings and contraindications (a blocking gap for safety screening)
- Detailed mechanism of action data
- Approved indication text and dosage forms for the Canadian licences
- If a perinatal HIV direction is pursued, a dedicated review of pregnancy safety and pharmacokinetic data
- A decision on whether an animal-model virus is a relevant target at all, given its limited relevance to human drug repurposing
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.