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 an HIV-1 reverse transcriptase inhibitor that is marketed in South Africa. The TxGNN model predicts it may be effective for simian immunodeficiency virus (SIV) infection, with a very high score. However, there are 0 clinical trials and only preclinical literature, so this looks more like a research-model use than a true repurposing indication.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | HIV-1 infection (the SAHPRA registration entries in the data have no indication text) |
| Predicted New Indication | Simian immunodeficiency virus infection |
| TxGNN Prediction Score | 99.85% |
| Evidence Level | L4 |
| South Africa Market Status | Marketed |
| Number of SAHPRA Registrations | 4 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not currently available in the record. Nevirapine is known to be a non-nucleoside reverse transcriptase inhibitor (NNRTI) that targets HIV-1 reverse transcriptase (RT). Its efficacy in HIV-1 is established, and SIV is a related lentivirus, so a graph model could plausibly link the two.
The link is weaker than the score suggests. Native SIV and HIV-2 RT are generally reported to be intrinsically insensitive to NNRTIs. The high score probably reflects HIV-related network proximity rather than true anti-SIV activity.
The literature shows activity mainly against RT-SHIV chimeras. These are SIV constructs carrying HIV-1 RT, and they are used as macaque models to study drug resistance. This supports using nevirapine in preclinical models, not as a treatment for SIV infection. This assessment is based on titles and truncated abstracts only.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 7541200 | 1995 | Preclinical in vitro | Biochem Biophys Res Commun | A hybrid SIV carrying the HIV-1 RT gene (RT-SHIV) was markedly sensitive to nucleoside and non-nucleoside RT inhibitors, unlike wild-type SIV |
| 15564466 | 2004 | Preclinical in vitro | J Virol | NNRTIs do not effectively inhibit SIV RT; an SIV-HIV chimera expressing HIV-1 RT was characterised to study NNRTI resistance in pigtail macaques |
| 11375059 | 2001 | Preclinical animal model | AIDS Res Hum Retroviruses | RT-SHIV-infected cynomolgus monkeys were used as an in vivo model of RT-inhibitor resistance development |
| 15040537 | 2004 | Preclinical in vitro | Antivir Ther | Compared 16 approved anti-HIV drugs against HIV-2, SIV and SHIV, to guide treatment and postexposure prophylaxis |
| 19195672 | 2009 | Preclinical animal model | Virology | RT-SHIV (with HIV-1 RT) transmitted efficiently by the vaginal route in rhesus macaques, supporting its use as a model |
| 16859727 | 2006 | Not classified (in vitro) | Virology | NRTIs and NNRTIs were tested for inactivating HIV-1 and SIV virions through endogenous reverse transcription |
| 11020686 | 2000 | Review | Ann Emerg Med | Non-occupational HIV postexposure prophylaxis; indirect support comes from animal studies with antiretrovirals against SIV |
| 27748043 | 2017 | Preclinical in vitro (other compound) | Chem Biol Drug Des | A different compound (3G11) blocked HIV-1 but not SIVmac; not evidence for nevirapine |
| 12234864 | 2002 | Preclinical in vitro (other compound) | Antimicrob Agents Chemother | Integrase inhibitor combined with nevirapine was subsynergistic; not evidence of nevirapine activity against SIV |
South Africa Market Information
| Registration Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| Reg. No. A40/20.2.8/0659 | Sonke-Laminevstav 30 | Tablet | Not stated in the registration data |
| Reg. No. 45/20.2.8/0388 | Mivirdo | Tablet | Not stated in the registration data |
| Reg. No. 44/20.2.8/0212 | Tri-Nestlam 150/30/200 | Tablet | Not stated in the registration data |
| Reg. No. 46/20.2.8/0943 | Nevasta | Tablet | Not stated in the registration data |
All four registrations are oral tablets. Essential Medicines List (EML) status is not included in the data provided and should be checked against the current EML.
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 preclinical work (L4) with no clinical trials. The literature mainly supports nevirapine’s use in macaque RT-SHIV models, and native SIV is generally insensitive to NNRTIs. The high TxGNN score therefore likely reflects network proximity rather than a real therapeutic opportunity. SIV infection is also not a human disease, so it is not a clinically actionable indication for South African patients.
The other two predictions for this drug are also on Hold:
- Feline acquired immunodeficiency syndrome (L4): one 2023 biochemical and structural comparison of NNRTIs against feline and human immunodeficiency viruses. This is a veterinary condition with no trials.
- A rare neurodevelopmental disorder (L5): no trials, no literature and no identifiable mechanistic rationale. This is likely a graph-prediction artifact.
To proceed, the following is needed:
- SAHPRA Professional Information (PI) warnings and contraindications, currently a blocking gap for safety screening
- Mechanism of action data from DrugBank
- Full-text review of the RT-SHIV literature to confirm the findings, since this assessment is based on titles and truncated abstracts
- Approved indication text for the four SAHPRA registrations
- An independent mechanistic review of the third prediction before any further work
This report is for research reference only and does not constitute medical advice. Repurposing candidates require clinical validation before any clinical use.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.