Efavirenz
| Evidence Level: L4 | Predicted Indications: 3 |
Table of Contents
Efavirenz: From HIV-1 Infection to Simian Immunodeficiency Virus Infection
One-Sentence Summary
Efavirenz is a non-nucleoside reverse transcriptase inhibitor (NNRTI) used against HIV-1 infection. The TxGNN model predicts it may be effective for Simian Immunodeficiency Virus (SIV) Infection, a non-human primate disease. Support is limited to 1 withdrawn clinical trial (no participants enrolled) and 15 publications, all preclinical or in vitro. There is no human efficacy evidence for this indication.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | HIV-1 infection (registration indication text was not supplied in the data) |
| Predicted New Indication | Simian immunodeficiency virus infection |
| TxGNN Prediction Score | 99.80% |
| Evidence Level | L4 |
| South Africa Market Status | Marketed |
| Number of SAHPRA Registrations | 14 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not currently available in the input. Efavirenz is a known HIV-1 NNRTI: it acts on HIV-1 reverse transcriptase (RT), and its efficacy in HIV-1 infection is established.
The macaque studies use RT-SHIV, a chimeric virus in which the SIV RT is replaced by HIV-1 RT. This makes the virus susceptible to efavirenz. Wild-type SIV is generally not NNRTI-susceptible. The literature therefore uses efavirenz as a tool drug in a primate model of HIV-1 therapy. It does not show a new indication.
SIV is a virus of non-human primates, so this prediction is not a realistic human repurposing opportunity. The high score (about 0.998) most likely reflects graph proximity among retroviral nodes in the knowledge graph. The evidence is indirect (animal and in vitro only).
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT00863668 | NA | Withdrawn | 0 | Decay kinetics of HIV with raltegravir in HIV-1 infection. It is not about SIV and efavirenz is not the study drug. No data were produced. |
No SANCTR or PACTR registrations were identified.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 15328115 | 2004 | Preclinical animal study | Antimicrob Agents Chemother | Evaluated efavirenz in rhesus macaques infected with RT-SHIV, which is NNRTI-susceptible unlike SIV |
| 15919889 | 2005 | Preclinical animal study | J Virol | Efavirenz + lamivudine + tenofovir in 7 RT-SHIV macaques; plasma viral RNA fell in all animals |
| 15040537 | 2004 | In vitro study | Antivir Ther | Compared activity of approved anti-HIV drugs against HIV-2, SIV and SHIV strains |
| 21084490 | 2011 | Preclinical animal study | J Virol | Viral genetic diversity persisted in macaques despite ART; some animals received short efavirenz monotherapy first |
| 19889213 | 2009 | Preclinical animal study | Retrovirology | Tracked viral subpopulations in macaques on efavirenz monotherapy followed by combination ART |
| 22933296 | 2012 | Preclinical animal study | J Virol | Ultrasensitive PCR detected rare pre-existing drug-resistant variants in RT-SHIV macaques |
| 24777106 | 2014 | Preclinical animal study | Antimicrob Agents Chemother | Four- and five-drug regimens improved early viral decay kinetics in RT-SHIV macaques |
| 20668516 | 2010 | Preclinical animal study | PLoS One | Characterised viral decay kinetics in a HAART-treated rhesus macaque model of AIDS |
| 26559632 | 2015 | Preclinical animal study | Retrovirology | Plasma and tissue viral populations were well mixed, suggesting little tissue replication during ART |
| 35856680 | 2022 | Preclinical imaging study | Antimicrob Agents Chemother | Imaged the spatial relationship between six antiretrovirals, viral RNA and fibrosis in macaque spleen |
South Africa Market Information
Efavirenz has 14 SAHPRA registrations; the main ones are listed below. The approved-indication text was not supplied in the data, so that column is omitted.
| Registration Number | Product Name | Dosage Form |
|---|---|---|
| Reg. No. 42/20.2.8/0979 | Adco-efavirenz | Capsule |
| Reg. No. A40/20.2.8/0508 | Sonke-efavirenz | Tablet |
| Reg. No. A40/20.2.8/272 | Sonke-lamivudine | Tablet |
| Reg. No. 43/20.2.8/0363 | Hevaz | Tablet |
| Reg. No. 52/20.2.8/0062 | Triovir | Film-coated tablet |
A kit presentation is also registered.
Safety Considerations
Please refer to the SAHPRA-approved Professional Information (PI) for safety information. Report adverse drug reactions to SAHPRA.
Conclusion and Next Steps
Decision: Hold
Rationale: The evidence is limited to animal and in vitro studies in which efavirenz serves as a tool drug against an HIV-1 RT chimeric virus. The only registered trial was withdrawn with no participants. SIV is a non-human primate infection, so this is not a genuine new human indication.
The other two model predictions are also on hold. Feline acquired immunodeficiency syndrome (L4) has only an in vitro structural study, and the two supporting trials are human HIV-1 studies. The neurodevelopmental disorder prediction (L5) has no trials or literature.
To proceed, the following is needed:
- SAHPRA package insert warnings and contraindications (a blocking gap for safety screening)
- Mechanism of action data from DrugBank
- Confirmation of the registered indication text for the SAHPRA products
- A defined human-relevant question, since the current evidence does not support a human indication for this prediction
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.