Dolutegravir
| Evidence Level: L5 | 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 strand transfer inhibitor, already marketed in South Africa for HIV-1 infection. The TxGNN model predicts it may be effective for feline acquired immunodeficiency syndrome (FIV), a cat lentivirus infection. Support is indirect: 5 clinical trials (all in human HIV-1, none in cats) and 1 veterinary publication.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | HIV-1 infection (the SAHPRA indication text is blank in the record) |
| Predicted New Indication | Feline acquired immunodeficiency syndrome |
| TxGNN Prediction Score | 99.85% |
| Evidence Level | L4 (preclinical/veterinary only) |
| South Africa Market Status | Marketed |
| Number of SAHPRA Registrations | 20 |
| Recommended Decision | Hold (research question) |
Why is This Prediction Reasonable?
Dolutegravir blocks the viral integrase enzyme, which inserts viral DNA into the host genome. FIV is a lentivirus related to HIV, and it causes progressive immune failure in cats that resembles AIDS. Blocking integration is therefore a plausible way to slow FIV. Related evidence from the simian model (SIV in macaques) shows that integrase inhibitors, including dolutegravir, act on a lentivirus outside humans.
Detailed mechanism of action data is not available in the record. Dolutegravir’s efficacy in HIV-1 is well established, and mechanistically it may be applicable to FIV. However, the integrase sequences of FIV and HIV-1 differ, so activity in cats is not established by the data supplied.
The one veterinary study, from 2023, tested dolutegravir inside a three-drug regimen in FIV-infected cats. The provided abstract is truncated, so its clinical results cannot be summarised here.
Clinical Trial Evidence
All trials below are in human HIV-1. They support the drug’s antiviral efficacy and safety in its source disease, not efficacy in cats.
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT01231516 | Phase 3 | Completed | 724 | Dolutegravir vs raltegravir in treatment-experienced, integrase-inhibitor-naïve adults (48 weeks) |
| NCT01227824 | Phase 3 | Completed | 828 | Dolutegravir vs raltegravir with dual NRTI backbone in treatment-naïve adults (96 weeks) |
| NCT01263015 | Phase 3 | Completed | 844 | Dolutegravir + abacavir/lamivudine vs Atripla in treatment-naïve adults (96 weeks) |
| NCT00951015 | Phase 2 | Completed | 208 | Phase IIb once-daily dose selection with two NRTI backbones |
| NCT01499199 | Phase 3 | Completed | 13 | Single-arm study of plasma and cerebrospinal fluid pharmacokinetics with abacavir/lamivudine |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 37112803 | 2023 | Preclinical/veterinary | Viruses | Pharmacokinetics and clinical outcomes of combination ART (dolutegravir 2.5 mg/kg, tenofovir 20 mg/kg, emtricitabine 40 mg/kg) in FIV-infected domestic cats; abstract truncated in the record |
South Africa Market Information
Twenty registrations are on file; the five main ones are shown. Approved indication text is not recorded for any of them.
| Registration Number | Product Name | Dosage Form |
|---|---|---|
| Reg. No. 56/20.2.8/0018 | Odinsti Dispersible Tablets | Orally disintegrating tablet (ODT) |
| Reg. No. 51/20.2.8/1032.1031 | Dalimune | Tablet |
| Reg. No. 52/20.2.8/0002.001 | Hetvir 50 | Film-coated tablet |
| Reg. No. 54/20.2.8/0642.641 | Lomida | Tablet |
| Reg. No. 55/20.2.8/0301 | Daliduo | Film-coated tablet |
An effervescent tablet form is also listed among the registered dosage forms.
Safety Considerations
Please refer to the SAHPRA-approved Professional Information (PI) for safety information. Report adverse drug reactions to SAHPRA.
Note for any neurodevelopmental use: neural tube defect signals in pregnancy (Tsepamo study, Botswana) have been reported with dolutegravir and would need careful review.
Conclusion and Next Steps
Decision: Hold
Rationale: The high TxGNN score is supported only by human HIV-1 trials and a single veterinary study whose results we could not review. Cross-species activity against FIV integrase is not established. Nothing in the record indicates a human clinical use for this prediction, so it remains a research question.
To proceed, the following is needed:
- Full review of the 2023 FIV cat study (PMID 37112803), including efficacy, dosing and safety outcomes
- Integrase sequence and in vitro susceptibility data for dolutegravir against FIV
- SAHPRA Professional Information (warnings and contraindications), currently missing and blocking safety screening
- Mechanism of action data from DrugBank
- Confirmation of the regulatory pathway for any veterinary use, since SAHPRA registrations cover human medicines
Other predictions in the pack:
- Simian immunodeficiency virus infection (Hold, L4): Macaque studies support the integrase mechanism. SIV is an animal model, so this backs the existing HIV-1 use rather than a new human target.
- Neurodevelopmental disorder with ataxic gait, absent speech, and decreased cortical white matter (Hold, L5): There is no supporting trial or literature and no plausible mechanistic link. It is likely a knowledge-graph artifact and needs manual review.
This report is for research reference only and does not constitute medical advice. Repurposing candidates require clinical validation before any application.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.