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Updated: May 5, 2026
10:29
Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors
Published on: May 9, 2025
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[Resistance profile of rilpivirine]
Arkaitz Imaz1, Federico García, Silvana di Yacovo
1Unidad de VIH, Servicio de Enfermedades Infecciosas, Hospital Universitari de Bellvitge, L'Hospitalet de Llobregat, Barcelona, España.
Enfermedades Infecciosas Y Microbiologia Clinica
|November 21, 2013
Summary
Rilpivirine (RPV), a second-generation nonnucleoside reverse transcriptase inhibitor (NNRTI), shows low virologic failure rates in treatment-naïve HIV-1 patients. However, emerging resistance mutations like E138K can lead to cross-resistance with other NNRTIs.
Area of Science:
- Virology
- Pharmacology
- Infectious Diseases
Context:
- Rilpivirine (RPV) is a second-generation nonnucleoside reverse transcriptase inhibitor (NNRTI) for HIV-1 treatment.
- Approved for treatment-naïve patients with viral load ≤100,000 copies/mL in combination with two nucleoside/nucleotide reverse transcriptase inhibitors (NRTI).
- RPV exhibits potent in vitro activity against HIV-1 variants with first-generation NNRTI resistance mutations.
Purpose:
- To identify mutations associated with RPV resistance.
- To assess the virologic failure risk and resistance patterns in patients receiving RPV plus 2 NRTI.
- To understand the cross-resistance profiles of RPV resistance mutations.
Summary:
- 16 mutations conferring RPV resistance were identified in vitro and in clinical trials.
- Virologic failure risk is low, but emergent resistance mutations (e.g., E138K) are common upon failure.
- E138K often co-occurs with M184I, conferring resistance to RPV and NRTIs like lamivudine and emtricitabine.
- RPV resistance leads to cross-resistance with other NNRTIs, including etravirine.
Impact:
- Identifies specific mutations linked to RPV resistance, aiding in monitoring and treatment decisions.
- Highlights the potential for cross-resistance, informing the selection of alternative antiretroviral therapies.
- Provides crucial data for understanding HIV-1 NNRTI resistance mechanisms and developing future treatment strategies.
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