Dolutegravir
| Evidence Level: L4 | Predicted Indications: 3 |
Table of Contents
- Dolutegravir
- Pharmacist Assessment Report
- Dolutegravir: From HIV Infection to Simian Immunodeficiency Virus Infection
- One-Sentence Summary
- Quick Overview
- Why is This Prediction Reasonable?
- Clinical Trial Evidence
- Literature Evidence
- Australia Market Information
- Safety Considerations
- Conclusion and Next Steps
- Disclaimer
Dolutegravir: From HIV Infection to Simian Immunodeficiency Virus Infection
One-Sentence Summary
Dolutegravir is an integrase strand transfer inhibitor originally used to treat HIV infection and AIDS. The TxGNN model predicts it may be effective for simian immunodeficiency virus (SIV) infection, with no registered clinical trials and 14 publications (almost entirely preclinical macaque and in vitro work) supporting this direction. This is an animal-model or research use, not a new human indication.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | HIV infectious disease; AIDS (the ARTG entry in the data compiled for this report has no indication text) |
| Predicted New Indication | Simian immunodeficiency virus infection |
| TxGNN Prediction Score | 0.9985 |
| Evidence Level | L4 |
| Australia Market Status | Listed on the PBS Schedule (1 of 1 items) – TGA (ARTG) registration status is not included in this data |
| Number of PBS Items | 1 (valid: 1) |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available in the data compiled for this report. From general knowledge, dolutegravir is an HIV-1 integrase strand transfer inhibitor that blocks viral DNA integration into the host genome.
SIV is a lentivirus closely related to HIV and encodes a similar integrase. Preclinical studies show that SIVmac239 is susceptible to integrase inhibitors and that integrase resistance mutations behave similarly in both viruses. Dolutegravir monotherapy in SIV-infected macaques selected for resistance mutations with variable virological outcomes. The prediction is therefore mechanistically plausible, but it essentially restates the approved HIV mechanism in an animal model. It does not represent a new human therapeutic indication.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
Fourteen publications were retrieved; the most relevant are listed below. All are preclinical or non-interventional, and several are off-topic.
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 30381490 | 2019 | Preclinical (macaque) | J Virol | Dolutegravir monotherapy in SIV-infected macaques selected several resistance mutation patterns with variable virological outcomes |
| 36365101 | 2022 | Preclinical (NHP) | Pharmaceutics | Pharmacological validation of long-term antiretroviral treatment, including dolutegravir, in SIVmac251-infected non-human primates |
| 26150024 | 2016 | Preclinical (macaque) | AIDS Res Hum Retroviruses | Compared coformulated injectable combination ART regimens in SIVmac239-infected rhesus macaques |
| 26378179 | 2015 | Preclinical (in vitro) | J Virol | Integrase inhibitor resistance profiles in SIVmac239 resemble those seen in HIV |
| 24920794 | 2014 | Preclinical (in vitro) | J Virol | HIV integrase resistance mutations introduced into SIVmac239 altered susceptibility to integrase inhibitors similarly |
| 25583721 | 2015 | Preclinical (SHIV model) | Antimicrob Agents Chemother | Simian-tropic HIV proposed as a model for integrase inhibitor resistance |
| 32506843 | 2021 | Review | FEBS J | HIV/SIV intasome structures clarify integrase inhibitor binding and viral escape |
| 34903055 | 2021 | Preclinical (macaque) | mBio | Lentiviral infection persists in the brain despite effective ART |
| 40093003 | 2025 | Preclinical (macaque imaging) | Front Immunol | Brain imaging changes in macaques before and after emtricitabine, tenofovir and dolutegravir treatment |
| 41959211 | 2026 | Preclinical (preprint) | bioRxiv | SIV and ART affect rhesus macaque brain lipid distribution |
Australia Market Information
| ARTG Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| ARTG 10283F | Tivicay | Tablet 50 mg (as sodium) | Not provided in the data compiled for this report |
Safety Considerations
- Drug Interactions: 62 interactions were identified in the data compiled for this report. Most of those listed are Major and involve polyvalent cation products that can reduce dolutegravir absorption: aluminium hydroxide, magaldrate, kaolin, attapulgite, calcium salts (acetate, carbonate, citrate, gluconate, lactate, phosphate, glubionate), magnesium salts (carbonate, chloride, citrate) and iron. Minor interactions include aprepitant, cimetidine, clarithromycin, clotrimazole and dexamethasone.
- Pregnancy: The literature compiled for this report describes a neural tube defect signal with dolutegravir exposure around conception, which later surveillance studies have examined further. This is relevant to any use in women of child-bearing potential.
Please refer to the TGA-approved Product Information (PI) for full warnings and contraindications.
Conclusion and Next Steps
Decision: Hold
Rationale: The prediction rests on preclinical macaque and in vitro data only, with no clinical trials. SIV infection is not a human disease, so it is a research-model use of the already approved HIV mechanism rather than a repurposing opportunity for Australian patients.
To proceed, the following is needed:
- Clarification of whether a human indication exists. If not, the finding is better treated as a research tool for non-human primate HIV models.
- Mechanism of action data and the TGA Product Information warnings and contraindications.
- If a nearby human indication is of interest (for example HIV in pregnancy or paediatric HIV), a separate evaluation that includes the neural tube defect safety data.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.