Sub-Epidemics Explain Localized High Prevalence of Reduced Susceptibility to Rilpivirine in Treatment-Naive HIV-1-Infected Patients: Subtype and Geographic Compartmentalization of Baseline Resistance Mutations

Objective: The latest nonnucleoside reverse transcriptase inhibitor (NNRTI) rilpivirine (RPV) is indicated for human immunodeficiency virus type-1 (HIV-1) patients initiating antiretroviral treatment, but the extent of genotypic RPV resistance in treatment-naive patients outside clinical trials is poorly defined. Study Design: This retrospective observational study of clinical data from Belgium and Portugal evaluates genotypic information from HIV-1 drug-naive patients obtained for the purpose of drug resistance testing. Rilpivirine resistance-associated mutations (RPV-RAMs) were defined based on clinical trials, phenotypic studies, and expert-based resistance algorithms. Viral susceptibility to RPV alone and to the single-tablet regimen was estimated using expert-based resistance algorithms. Results: In 4,631 HIV-1 treatment-naive patients infected with diverse HIV-1 subtypes, major RPV-RAMs were detected in 4.6%, while complete viral susceptibility to RPV was estimated in 95% of patients. Subtype C- and F1-infected patients displayed the highest levels of reduced viral susceptibility at baseline, respectively 13.2% and 9.3%, mainly due to subtype- and geographic-dependent occurrence of RPV-RAMs E138A and A98G as natural polymorphisms. Strikingly, a founder effect in Portugal resulted in a 138A prevalence of 13.2% in local subtype C-infected treatment-naive patients. The presence of transmitted drug resistance did not impact our estimates. Conclusion: RPV is the first HIV-1 inhibitor for which, in the absence of transmitted drug resistance, intermediate or high-level genotypic resistance can be detected in treatment-naive patients. The extent of RPV susceptibility in treatment-naive patients differs depending on the HIV-1 subtype and dynamics of local compartmentalized epidemics. The highest prevalence of reduced susceptibility was found to be 15.7% in Portuguese subtype C-infected treatment-naive patients. In this context, even in the absence of transmitted HIV-1 drug resistance (TDR), drug resistance testing at baseline should be considered extremely important before starting treatment with this NNRTI. © Kristof Theys, et al., 2016; Published by Mary Ann Liebert, Inc. 2016.

• Fecha de publicación: 2016
• Institución: Universidad del Rosario
• Repositorio: Repositorio EdocUR - U. Rosario
• Idioma: eng
• OAI Identifier: oai:repository.urosario.edu.co:10336/23941
• Acceso en línea: https://doi.org/10.1089/aid.2015.0095; https://repository.urosario.edu.co/handle/10336/23941
• Palabra clave: Rilpivirine; Anti human immunodeficiency virus agent; Rilpivirine; Rna directed dna polymerase inhibitor; Antiviral resistance; Antiviral susceptibility; Article; Belgium; Epidemic; Founder effect; Genotype; Geographic distribution; Human; Human immunodeficiency virus 1; Human immunodeficiency virus 1 infection; Human immunodeficiency virus infected patient; Major clinical study; Nonhuman; Observational study; Portugal; Prevalence; Priority journal; Resistance associated mutation; Retrospective study; Tablet; Virus mutation; Virus resistance; Drug effects; Genetics; Highly active antiretroviral therapy; Hiv infections; Mutation; Procedures; Single nucleotide polymorphism; Anti-hiv agents; Belgium; Founder effect; Genotype; Hiv infections; Hiv-1; Humans; Mutation; Portugal; Retrospective studies; Reverse transcriptase inhibitors; Rilpivirine; viral; single nucleotide; highly active; Antiretroviral therapy; Drug resistance; Polymorphism
• License: Abierto (Texto Completo)