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Virological Failure After Switch to Long-Acting Cabotegravir and Rilpivirine Injectable Therapy: An In-depth Analysis
Berend J van Welzen1, Steven F L Van Lelyveld2, Gerjanne Ter Beest3
1Department of Infectious Diseases, University Medical Center Utrecht, Utrecht, The Netherlands.
Summary
Virological failure (VF) in long-acting injectable cabotegravir (CAB) and rilpivirine (RPV) therapy for HIV-1 can occur due to low drug levels and resistance mutations. Comprehensive analysis is crucial for managing such cases.
Area of Science:
- Infectious Diseases
- Pharmacology
- Virology
Background:
- Long-acting (LA) injectable cabotegravir (CAB) and rilpivirine (RPV) is a maintenance therapy for HIV-1 with a low risk of virological failure (VF).
- Real-world circumstances and impact of VF require further investigation.
Purpose of the Study:
- To conduct an in-depth analysis of VF in patients receiving LA CAB/RPV therapy.
- To identify reasons for VF, including virological, clinical, and pharmacokinetic factors.
Main Methods:
- Analysis of 5 cases of VF in the Netherlands.
- Genotypic resistance testing and measurement of plasma drug concentrations (trough levels).
- Identification of low drug levels (≤Q1) and resistance mutations.
Main Results:
- All 5 cases experienced VF despite low predicted risk.
- Extensive selection of nonnucleoside reverse transcriptase inhibitor (NNRTI) mutations and integrase strand transfer inhibitor (INSTI) mutations observed.
- Low drug levels of CAB, RPV, or both were present in all cases, contributing to VF.
Conclusions:
- This is the first in-depth case analysis of VF on LA CAB/RPV in a real-world setting.
- Highlights the need for awareness of evolving risk factors for VF.
- Emphasizes the value of a comprehensive clinical, virological, and pharmacokinetic approach in managing treatment failure.
