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
Van Laethem, Kristel
Camacho, Ricardo J.
Abecasis, Ana B.
"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."
Rilpivirine ; Anti human immunodeficiency virus agent ; viral ; single nucleotide ; highly active ; 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 ; Antiretroviral therapy ; Belgium ; Drug resistance ; Founder effect ; Genotype ; Hiv infections ; Hiv-1 ; Humans ; Mutation ; Polymorphism ; Portugal ; Retrospective studies ; Reverse transcriptase inhibitors ; Rilpivirine ;
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