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Updated: May 4, 2026
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Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors
Published on: May 9, 2025
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Immune activation throughout a boosted darunavir monotherapy simplification strategy.
O J BenMarzouk-Hidalgo1, A Torres-Cornejo, A Gutiérrez-Valencia
1Unidad Clínica de Enfermedades Infecciosas, Microbiología y Medicina Preventiva, Hospital Universitario Virgen del Rocío, Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Sevilla, Spain.
Summary
Ritonavir-boosted darunavir monotherapy is a safe HIV treatment simplification strategy. Viral blips do not impact immune activation, but virological failure increases it, especially with high baseline T-cell activation.
Area of Science:
- Immunology
- Virology
- HIV/AIDS Research
Background:
- Ritonavir-boosted darunavir monotherapy (mtDRV/rtv) is explored as a simplification strategy for HIV-1 infected patients.
- Understanding the impact of viral blips and virological failure (VF) on immune activation (IA) is crucial for long-term treatment success.
Purpose of the Study:
- To assess the evolution and impact of viral blips, intermittent low-level viraemia, and VF on immune activation profiles during mtDRV/rtv.
- To identify predictors of VF in patients on mtDRV/rtv.
Main Methods:
- Prospective cohort study (MonDAR) of 75 HIV-1 patients on mtDRV/rtv for 2 years.
- Assessed cellular IA (HLA-DR, CD38 on T-cell subsets) and systemic IA (sCD14, D-dimer).
- Classified patients into groups: continuous undetectable viraemia, blips, intermittent viraemia, and VF.
Main Results:
- Patients with sustained viral suppression showed decreased T-cell activation and IA markers.
- Transient low-level viraemia (blips, intermittent) had minimal impact on IA profiles.
- Virological failure was associated with significant increases in T-cell activation and systemic IA markers.
- High baseline HLA-DR(+)CD38(+)CD8(+) T-cells (>6.4%) independently predicted VF.
Conclusions:
- mtDRV/rtv is a safe simplification strategy when viral replication is controlled.
- Transient viraemia episodes do not negatively affect immune activation.
- Baseline T-cell activation levels are important considerations for switching to mtDRV/rtv to predict VF risk.
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