Doravirine
| Evidence Level: L4 | Predicted Indications: 10 |
Table of Contents
Doravirine: From HIV-1 Infection to Simian Immunodeficiency Virus Infection
One-Sentence Summary
Doravirine (DrugBank DB12301) is a non-nucleoside reverse transcriptase inhibitor (NNRTI) used to treat HIV-1 infection. The TxGNN model predicts it may also be active against Simian Immunodeficiency Virus (SIV) infection, a related primate lentivirus, but this direction is currently supported by only 1 indirectly related publication and no clinical trials, making it a low-confidence, model-only signal.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | HIV-1 Infection (inferred from clinical trial context in this evidence pack; not a TFDA-approved indication, as the drug is not marketed in Taiwan) |
| Predicted New Indication | Simian Immunodeficiency Virus (SIV) Infection |
| TxGNN Prediction Score | 99.93% |
| Evidence Level | L4 |
| Taiwan Market Status | Not marketed (Not Marketed) |
| Number of Authorizations | 0 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Currently, a structured mechanism-of-action (MOA) record for Doravirine is not available in this evidence pack (flagged as a High-severity data gap, DG002). Based on the mechanistic rationale attached to its predicted indications, Doravirine is a non-nucleoside reverse transcriptase inhibitor (NNRTI) that binds and blocks the reverse transcriptase enzyme of HIV-1, preventing conversion of viral RNA into DNA and halting viral replication.
SIV (Simian Immunodeficiency Virus) is a lentivirus closely related to HIV-1 that infects non-human primates and is widely used as an animal model for HIV research. Because SIV reverse transcriptase shares structural similarity with HIV-1 reverse transcriptase, there is a theoretical basis for NNRTI activity extending across the two viruses. This is, however, an indirect taxonomic analogy rather than a finding derived from direct preclinical or clinical testing of Doravirine against SIV.
It is also important to note that the single supporting literature record (PMID 31658118) is a 2020 review discussing Islatravir, a different investigational NNRTI-class antiretroviral — not Doravirine itself. The evidence therefore reflects thematic relevance to the reverse-transcriptase-inhibitor drug class rather than a direct study of Doravirine in an SIV context. This substantially weakens confidence in the prediction despite its mechanistic plausibility.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 31658118 | 2020 | Review | Current Opinion in HIV and AIDS | Discusses islatravir, a related NNRTI-class investigational agent, in the treatment/prevention of HIV-1; does not directly study Doravirine or SIV. |
Taiwan Market Information
Doravirine is currently not marketed in Taiwan (0 authorizations on record), so no license/product information is available.
Safety Considerations
Please refer to the SmPC / TFDA package insert for safety information (key warnings, contraindications, and drug-interaction data were not available in this evidence pack — DG001, Blocking severity).
Conclusion and Next Steps
Decision: Hold
Rationale: The prediction score is high, but the supporting evidence is weak and indirect — there are no clinical trials, and the single literature citation concerns a different drug (Islatravir) rather than Doravirine. Without direct preclinical or clinical data linking Doravirine to SIV, this candidate cannot advance past an initial research hypothesis stage.
To proceed, the following is needed:
- Doravirine MOA confirmation via DrugBank/primary literature (DG002)
- TFDA label warnings/contraindications for baseline safety screening (DG001, Blocking — currently prevents any S1 safety evaluation)
- Direct in-vitro or preclinical evidence of Doravirine activity against SIV reverse transcriptase
- Drug-drug interaction (DDI) data, currently unavailable (query returned “not_found”)
Additional note: Within this same evidence pack, a different predicted indication — congenital human immunodeficiency virus (rank 5, TxGNN score 98.75%, Evidence Level L2, decision stage S2, “Research Question”) — is supported by 5 clinical trials, including a completed Phase 3 pivotal trial (NCT02397096) and a dedicated pregnancy pharmacokinetics study (NCT04518228). This candidate, addressing mother-to-child HIV transmission prevention, is considerably more clinically mature than the SIV signal and may warrant separate, prioritized evaluation.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.