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

Kristof Theys, Kristel van Laethem, Perpetua Gomes, Guy Baele, Andrea-Clemencia Pineda-Peña, Anne-Mieke Vandamme, Ricardo Jorge Camacho, Ana B Abecasis

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)427-33
Number of pages7
JournalAIDS Research and Human Retroviruses
Volume32
Issue number5
DOIs
Publication statusPublished - May 2016

Keywords

  • Anti-HIV Agents
  • Antiretroviral Therapy, Highly Active
  • Belgium
  • Drug Resistance, Viral
  • Founder Effect
  • Genotype
  • HIV Infections
  • HIV-1
  • Humans
  • Mutation
  • Polymorphism, Single Nucleotide
  • Portugal
  • Retrospective Studies
  • Reverse Transcriptase Inhibitors
  • Rilpivirine
  • Journal Article
  • Observational Study
  • Research Support, Non-U.S. Gov't

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