Prevalence of genotypic baseline risk factors for cabotegravir + rilpivirine failure among ARV-naive patients
| Autor: | Charlotte Charpentier, Sidonie Lambert-Niclot, Marc Wirden, Karine Lacombe, Anne-Geneviève Marcelin, Valentine Marie Ferré, Alexandre Storto, Jade Ghosn, Romain Palich, Christine Katlama, Roland Landman, V Joly, Diane Descamps, Laurence Morand-Joubert, Vincent Calvez, Cathia Soulié |
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| Rok vydání: | 2021 |
| Předmět: |
Microbiology (medical)
medicine.medical_specialty Anti-HIV Agents Pyridones Baseline risk HIV Infections Drug resistance Therapy naive chemistry.chemical_compound Cabotegravir Risk Factors Polymorphism (computer science) Internal medicine Drug Resistance Viral Genotype Prevalence medicine Humans Pharmacology (medical) Pharmacology business.industry Rilpivirine Infectious Diseases chemistry HIV-1 Genotypic resistance business |
| Zdroj: | Journal of Antimicrobial Chemotherapy. 76:2983-2987 |
| ISSN: | 1460-2091 0305-7453 |
| DOI: | 10.1093/jac/dkab161 |
| Popis: | Background Multivariable baseline factor analysis across cabotegravir + rilpivirine clinical trials showed that HIV-1 subtypes A6/A1 and the presence of rilpivirine resistance-associated mutations (RAMs) were associated with an increased risk of virological failure of this dual therapy. The aim of this study was to describe the prevalence of genotypic baseline risk factors for cabotegravir + rilpivirine failure among ARV-naive patients. Patients and methods From 2010 to 2020, 4212 sequences from ARV-naive patients were collected from three large Parisian academic hospital genotypic databases. Cabotegravir and rilpivirine RAMs were defined according to the ANRS algorithm. Results Among 4212 ARV-naive patients, 38.6% were infected with subtype B, 32.4% with CRF02_AG (32.4%) and 5.1% with subtype A (85.5% being A6/A1 subtype). Overall, the presence of at least one cabotegravir or rilpivirine RAM was 16.2% and 14.3%, respectively. Considering genotypic resistance interpretation, using the ANRS algorithm, 0.74% (n = 31), 6.2% (n = 261) and 0.09% (n = 4) of sequences were resistant to cabotegravir, rilpivirine or both, respectively. The overall prevalence of L74I in integrase and E138A in RT was 13.0% and 3.2%, respectively, and stable over the decade. Thus, adding 183 subtype A6/A1 sequences to 244 sequences interpreted as resistant to rilpivirine led to 427 (10.1%) sequences combining both baseline virological risk factors for cabotegravir + rilpivirine dual-therapy failure. Conclusions Among large sequence databases, when adding prevalence of rilpivirine-resistant viruses and HIV-1 subtype A6/A1 sequences, 10.1% of patients would not be eligible for cabotegravir + rilpivirine dual therapy. These data re-emphasize the need for a pre-therapeutic genotypic resistance test to detect polymorphisms and transmitted drug resistance and to define HIV-1 subtype. |
| Databáze: | OpenAIRE |
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