Dolutegravir
| Evidence Level: L4 | Predicted Indications: 3 |
Table of Contents
Dolutegravir: From HIV-1 Infection to Feline Acquired Immunodeficiency Syndrome
One-Sentence Summary
Dolutegravir is an HIV-1 integrase inhibitor. The license records in the pack list no indication text, so HIV-1 is inferred from the linked trials. The TxGNN model predicts it may be effective for feline acquired immunodeficiency syndrome (FIV infection in cats). The five linked clinical trials are all human HIV-1 studies, so they support this only indirectly. The only direct evidence is 1 preclinical publication in FIV-infected cats.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | HIV-1 infection (inferred from linked trials; no approved indication text in the license records) |
| Predicted New Indication | Feline acquired immunodeficiency syndrome |
| TxGNN Prediction Score | 99.85% |
| Evidence Level | L4 |
| US Market Status | ✓ Marketed |
| Number of NDAs | 3 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available in the pack. Dolutegravir is an HIV-1 integrase strand-transfer inhibitor. Its efficacy against HIV-1 is shown in the human trials below.
FIV is a lentivirus closely related to HIV. It causes progressive immune dysfunction in cats and also depends on an integrase enzyme. Integrase inhibition is therefore mechanistically plausible. The very high TxGNN score most likely reflects this HIV-related proximity in the knowledge graph.
Two caveats apply. First, FIV is a veterinary disease, so direct evidence has to come from cats, and no clinical trial in cats is registered. Second, cross-species transfer of efficacy and dosing is unproven.
Clinical Trial Evidence
All trials below are in humans with HIV-1. They show that dolutegravir works in a related human lentivirus but say nothing about FIV in cats.
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT01263015 | Phase 3 | Completed | 844 | Dolutegravir + abacavir/lamivudine vs Atripla in treatment-naive adults; non-inferiority tested at Weeks 48 and 96 |
| NCT01227824 | Phase 3 | Completed | 828 | Dolutegravir once daily vs raltegravir twice daily in treatment-naive adults; non-inferiority over 96 weeks |
| NCT01231516 | Phase 3 | Completed | 724 | Dolutegravir vs raltegravir in treatment-experienced, integrase-inhibitor-naive adults; 48-week non-inferiority |
| NCT00951015 | Phase 2 | Completed | 208 | Phase IIb once-daily dose selection with two dual-NRTI backbones |
| NCT01499199 | Phase 3 | Completed | 13 | Single-arm study of central nervous system and plasma pharmacokinetics with abacavir/lamivudine over 96 weeks |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 37112803 | 2023 | Preclinical/animal study (inferred from title) | Viruses | Evaluated pharmacokinetics and clinical outcomes of a combination antiretroviral regimen (dolutegravir 2.5 mg/kg, tenofovir 20 mg/kg, emtricitabine 40 mg/kg) in FIV-infected cats. The abstract in the pack is truncated, so outcomes are not confirmed here. |
US Market Information
| Authorization Number | Product Name | Dosage Form | Manufacturer |
|---|---|---|---|
| NDA213983 | Tivicay PD | Tablet, for suspension | ViiV Healthcare Company |
| NDA204790 | Tivicay | Tablet, film coated | ViiV Healthcare Company |
| NDA204790 | Tivicay | Tablet, film coated | St. Mary’s Medical Park Pharmacy |
All products are oral. The records carry no approved-indication text.
Safety Considerations
Please refer to the package insert for safety information.
Conclusion and Next Steps
Decision: Hold
Rationale: The mechanistic link is plausible, and the human HIV-1 data show the drug is effective and tolerated in people. However, no feline efficacy or dosing data is confirmed. The one cat study has only a truncated abstract, and the indication is veterinary. The pack rates this as a research question rather than a candidate for development.
The other two predictions are weaker. Simian immunodeficiency virus infection has only an indirect human trial in which dolutegravir is at most background therapy. The rare neurodevelopmental disorder has no evidence and no plausible mechanism.
To proceed, the following is needed:
- Full text of the 2023 feline study (PMID 37112803), including virological and clinical outcomes and pharmacokinetics
- Feline-specific dose, exposure and safety data
- Detailed mechanism of action data, plus any FIV integrase inhibition data
- Package insert warnings and contraindications
- A decision on whether a veterinary indication is in scope, since the human license records do not cover it
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.