Doravirine

Evidence Level: L5

Predicted Indications: 3

Doravirine

Pharmacist Assessment Report

Doravirine: From HIV Infection to Feline Acquired Immunodeficiency Syndrome

One-Sentence Summary

Doravirine is an antiviral originally used to treat HIV infection and AIDS. The TxGNN model predicts it may be effective for feline acquired immunodeficiency syndrome, but there are currently 0 clinical trials and 0 publications directly supporting this prediction, so it rests on model prediction alone.

Quick Overview

Item	Content
Original Indication	HIV infectious disease; AIDS
Predicted New Indication	Feline acquired immunodeficiency syndrome
TxGNN Prediction Score	0.9993
Evidence Level	L5
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 available in the data compiled for this report. Based on known information, doravirine is a non-nucleoside reverse transcriptase inhibitor (NNRTI) that acts against HIV-1. Its efficacy in HIV infection and AIDS is established, and the prediction is that it may be applicable to a related lentiviral disease.

Feline immunodeficiency virus (FIV) is a lentivirus related to HIV, so a mechanism targeting reverse transcriptase is conceivable. However, NNRTIs are generally poorly active against FIV because its reverse transcriptase differs structurally from that of HIV-1. No supporting data were available to resolve this question.

The high TxGNN score (0.9993) comes from the TxGNN model (deep learning) and may reflect similarities the model learned between related diseases, not biological evidence. It is not independent evidence of efficacy.

Other predictions:

Simian immunodeficiency virus infection (score 0.9993): SIV is closely related to HIV, so a rationale is plausible. The only linked publication concerns a different drug (islatravir), and SIV infection is mainly an animal research model rather than a human clinical indication.
Neurodevelopmental disorder with ataxic gait, absent speech, and decreased cortical white matter (score 0.9991): No plausible mechanistic link was identified. This is a rare genetic disorder with no viral target, and the score comes from the TxGNN model (deep learning) and may reflect similarities the model learned between related diseases, not biological evidence.

Clinical Trial Evidence

Currently no related clinical trials registered.

Literature Evidence

Currently no related literature available for feline acquired immunodeficiency syndrome.

For the second-ranked prediction (SIV infection), one review was linked, but it does not study doravirine:

PMID	Year	Type	Journal	Key Findings
31658118	2020	Review	Current Opinion in HIV and AIDS	Discusses islatravir, a different reverse transcriptase translocation inhibitor, for HIV-1 treatment and prevention. No direct evidence for doravirine.

Canada Market Information

DIN	Product Name	Dosage Form	Approved Indication
02481545	PIFELTRO	Not specified	Not specified
02482592	DELSTRIGO	Not specified	Not specified

Safety Considerations

Drug Interactions: 59 interactions were identified. Examples among those listed:

Major: Dexamethasone, Lumacaftor
Moderate: Glycerol phenylbutyrate, Metreleptin, Troglitazone, Deferasirox, Praziquantel, Griseofulvin
Minor: Aprepitant, Cimetidine, Clarithromycin, Clotrimazole, Miconazole, Cobicistat, Ticagrelor, Ivacaftor, Zafirlukast, Chloramphenicol, Erythromycin, Fluconazole

Please refer to the package insert for warnings and contraindications.

Conclusion and Next Steps

Decision: Hold

Rationale: The prediction is supported only by the TxGNN model score (evidence level L5), with no clinical trials or directly relevant literature. The mechanistic rationale is also weak: NNRTIs are generally poorly active against FIV, and feline and simian immunodeficiency are veterinary or animal-model conditions rather than human indications.

To proceed, the following is needed:

Health Canada package insert warnings and contraindications, which are required for safety screening
Detailed mechanism of action data for doravirine
Preclinical data on doravirine activity against FIV or SIV reverse transcriptase
Clarification of whether a veterinary or animal-model indication is relevant to the intended repurposing programme
A review of the major interactions (dexamethasone, lumacaftor) if the drug is developed further
Disclaimer

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