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), a mechanistic class of drug developed and used for HIV-1 infection. The TxGNN model predicts a possible link to Simian Immunodeficiency Virus (SIV) Infection, a non-human primate retroviral disease, but this is currently supported only by 17 in vitro/animal mechanistic publications and no clinical trials, and the accompanying mechanistic rationale itself flags the link as weak.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | HIV-1 infection (inferred from mechanistic rationale text; not independently confirmed by regulatory data in this evidence pack) |
| Predicted New Indication | Simian Immunodeficiency Virus Infection |
| TxGNN Prediction Score | 99.85% |
| Evidence Level | L4 |
| UK Market Status | Not marketed |
| Number of Marketing Authorisations | 0 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available in this evidence pack. Based on the mechanistic rationale supplied, Nevirapine is an HIV-1-specific NNRTI that binds a hydrophobic pocket unique to HIV-1 reverse transcriptase (RT); its efficacy in HIV-1 infection is well established in general clinical practice.
However, the supporting literature indicates this mechanism does not transfer well to SIV. SIV/SHIV are primate model viruses whose RT sequence and binding pocket differ substantially from HIV-1 RT. Several of the cited studies (e.g. PMID 7541200, PMID 15040537) specifically demonstrate that first-generation NNRTIs show markedly reduced or absent inhibitory activity against SIV compared with HIV-1. This means the TxGNN knowledge-graph association, while scoring highly, is built largely on studies that use SIV/SHIV as tools to study HIV-1 drug resistance rather than as a genuine therapeutic target for Nevirapine itself.
Two further predicted indications from the same evidence pack (Feline Acquired Immunodeficiency Syndrome, rank 2; and a rare neurodevelopmental disorder, rank 3) show similarly weak or absent mechanistic support — the neurodevelopmental disorder association in particular has no clinical trial or literature evidence whatsoever (Evidence Level L5) and is likely a knowledge-graph false positive. None of the three predictions are considered clinically actionable at this stage.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 27748043 | 2017 | In vitro mechanism study | Chemical Biology & Drug Design | Small-molecule HIV-1 RT inhibitor (3G11) does not block SIVmac, illustrating HIV-1 vs SIV specificity of NNRTI-class compounds |
| 15564466 | 2004 | In vitro chimeric virus characterisation | Journal of Virology | SIV-HIV chimera (RT-SHIV) built because NNRTIs do not effectively inhibit native SIV RT, enabling in vivo NNRTI resistance studies in macaques |
| 19195672 | 2009 | Animal model (macaque) | Virology | Vaginal transmission characterisation of RT-SHIV (HIV-1 RT inserted into SIV backbone) in rhesus macaques |
| 11020686 | 2000 | Review/clinical commentary | Annals of Emergency Medicine | HIV post-exposure prophylaxis review citing animal (including SIV) data indirectly supporting antiretroviral efficacy; not SIV-specific therapy |
| 7541200 | 1995 | In vitro resistance profiling | Biochemical and Biophysical Research Communications | RT-SHIV markedly sensitive to NNRTIs, whereas native SIV is inhibited only by nucleoside analogues — supports mechanistic mismatch |
| 11375059 | 2001 | In vivo animal model | AIDS Research and Human Retroviruses | Cynomolgus monkey RT-SHIV model used to study emergence of NNRTI drug resistance |
| 1283296 | 1992 | In vitro antiviral screening | Antimicrobial Agents and Chemotherapy | Nucleoside analogue (FTC, not an NNRTI) shown active against SIV; included as broader antiviral-screening context |
| 9875393 | 1998 | In vitro antiviral screening | Antiviral Chemistry & Chemotherapy | Fluoroquinolone derivative K-12 shows broad anti-HIV/SIV activity via a transcriptional mechanism distinct from NNRTIs |
| 15040537 | 2004 | In vitro comparative susceptibility | Antiviral Therapy | Systematic comparison of 16 approved anti-HIV-1 drugs (including NNRTIs) against HIV-2, SIV and SHIV strains, directly informing treatment/PEP implications |
| 12234864 | 2002 | In vitro mechanism study | Antimicrobial Agents and Chemotherapy | Integrase inhibitor combined with nevirapine tested against SIVmac; nevirapine combination noted as subsynergistic |
UK Market Information
No UK marketing authorisation data is present in this evidence pack (market status: Not marketed, 0 licences on record). No product-level information is currently available for review.
Safety Considerations
Please refer to the SmPC and BNF for safety information. Report suspected adverse reactions via the Yellow Card Scheme.
Note: a Blocking data gap exists — regulatory label warnings and contraindications for this drug are currently unavailable (DG001), which prevents any formal safety (S1) assessment.
Conclusion and Next Steps
Decision: Hold
Rationale: The evidence base is limited to mechanistic, in vitro and animal-model studies (Evidence Level L4) with no clinical trials, and the underlying literature itself indicates that NNRTIs such as Nevirapine have reduced or absent activity against SIV compared with HIV-1, undermining the mechanistic case. A Blocking data gap (missing label warnings/contraindications, DG001) also prevents progression to safety review at this time.
To proceed, the following is needed:
- Confirmed drug label warnings and contraindications (resolve DG001, Blocking)
- Confirmed mechanism of action data (resolve DG002)
- Confirmed original indication and regulatory history for Nevirapine
- Dedicated in vivo efficacy data demonstrating anti-SIV activity specifically for Nevirapine (not chimeric RT-SHIV models using HIV-1 RT)
- Reassessment against the two lower-ranked predictions (FIV, neurodevelopmental disorder), both of which show even weaker or no supporting evidence and are likely lower priority than SIV infection
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.