Nevirapine
| Evidence Level: L4 | Predicted Indications: 3 |
Table of Contents
Nevirapine: From HIV-1 Infection to Simian Immunodeficiency Virus Infection
One-Sentence Summary
Nevirapine is a non-nucleoside reverse transcriptase inhibitor (NNRTI) used to treat HIV-1 infection. The TxGNN model predicts it may be effective for simian immunodeficiency virus (SIV) infection, but there are 0 clinical trials and 15 publications, all preclinical or indirect. This prediction most likely reflects an animal-model or research use rather than a human therapeutic indication.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | HIV-1 infection (the US license records provided contain no indication text) |
| Predicted New Indication | Simian immunodeficiency virus infection |
| TxGNN Prediction Score | 99.85% |
| Evidence Level | L4 |
| US Market Status | ✓ Marketed |
| Number of NDAs | 9 (all listed records are ANDA generics) |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available in the record. Nevirapine is known as an NNRTI that acts on HIV-1 reverse transcriptase (RT). Its efficacy in HIV-1 infection is established, and HIV-1 is not counted as repurposing.
The relationship to SIV is weak. Wild-type SIV RT is naturally insensitive to NNRTIs, so direct activity against SIV is not expected. The literature mainly concerns chimeric viruses (RT-SHIV) that carry HIV-1 RT. These serve as animal models for testing NNRTIs and studying drug resistance, so they show nevirapine acting on HIV-1 RT and say nothing about treating SIV itself.
The high score most likely reflects the shared retroviral RT target and HIV-related neighbors in the knowledge graph, not an independent SIV indication. This is a research-model use, not a human therapeutic indication.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
No RCTs were found. The studies below are in vitro, animal-model or review papers. Key findings are summarized from the provided abstracts, some of which are truncated.
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 15564466 | 2004 | In vitro | Journal of Virology | NNRTIs do not effectively inhibit SIV RT, so an SIV chimera expressing HIV-1 RT was characterized to study NNRTI resistance in pigtail macaques |
| 7541200 | 1995 | In vitro | Biochem Biophys Res Commun | A hybrid SIV carrying HIV-1 RT (RT-SHIV) was markedly sensitive to NNRTIs, whereas SIV itself was not |
| 11375059 | 2001 | Animal study | AIDS Res Hum Retroviruses | Cynomolgus monkeys infected with RT-SHIV were used as an in vivo model of RT-inhibitor resistance development |
| 19195672 | 2009 | Animal study | Virology | An RT-SHIV transmitted efficiently by the vaginal route in rhesus macaques, supporting its use as a model |
| 15040537 | 2004 | Not classified | Antiviral Therapy | Compared 16 approved drugs against HIV-2, SIV and SHIV strains to inform treatment and post-exposure prophylaxis |
| 16859727 | 2006 | Not classified | Virology | NRTI and NNRTI pretreatment of HIV-1 and SIV virions was examined as a virucide approach |
| 11020686 | 2000 | Review | Annals of Emergency Medicine | HIV post-exposure prophylaxis, with indirect support from animal studies of antiretrovirals against SIV |
| 27748043 | 2017 | In vitro | Chem Biol Drug Des | The compound 3G11 blocked HIV-1 but not SIV or other retroviruses (indirect; not nevirapine) |
| 12234864 | 2002 | In vitro | Antimicrob Agents Chemother | An integrase inhibitor was subsynergistic with nevirapine and other drugs in cell culture (indirect) |
| 9875393 | 1998 | In vitro | Antiviral Chem Chemother | The fluoroquinolone K-12 was active against HIV-1, HIV-2 and SIV (indirect; not nevirapine) |
US Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| ANDA206879 | Nevirapine (Macleods) | Extended-release tablet | Not stated in provided data |
| ANDA205651 | Nevirapine (Mylan) | Extended-release tablet | Not stated in provided data |
| ANDA077521 | Nevirapine (Aurobindo) | Tablet | Not stated in provided data |
| ANDA078584 | Nevirapine (Camber) | Tablet | Not stated in provided data |
| ANDA077702 | Nevirapine (Aurobindo) | Suspension | Not stated in provided data |
Safety Considerations
Please refer to the package insert for safety information.
Conclusion and Next Steps
Decision: Hold
Rationale: Evidence is preclinical only (L4), with no registered trials. Wild-type SIV is naturally insensitive to NNRTIs, and the supporting papers use HIV-1 RT chimeras as research models. There is no human therapeutic case for this indication.
To proceed, the following is needed:
- Package insert warnings and contraindications for a safety screen
- Detailed mechanism of action data from DrugBank
- Confirmation of whether any direct nevirapine data against wild-type SIV exist, as opposed to RT-SHIV models
Other predictions (both Hold):
- Feline acquired immunodeficiency syndrome (L4): one 2023 in vitro biochemical and structural study compared NNRTIs, including nevirapine, against FIV RT. The nevirapine effect size could not be confirmed because the title was truncated. No efficacy data are available.
- Neurodevelopmental disorder with ataxic gait, absent speech, and decreased cortical white matter (L5): no trials, no literature and no plausible mechanism. This is likely a knowledge-graph artifact.
These results are for research reference only and do 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.