Rilpivirine Resistance Mutations in HIV Patients Failing Non-Nucleoside Reverse Transcriptase Inhibitor-Based Therapies

AIDS. 2013 Jan 2;27(1):81-5. doi: 10.1097/QAD.0b013e3283584500.

Abstract

Objective: Rilpivirine (RPV) is the latest approved nonnucleoside reverse transcriptase inhibitor (NNRTI). It displays in-vitro activity extending over other NNRTI-resistant HIV strains. There is scarce information about the rate of RPV resistance-associated mutations (RAMs) in patients failing other NNRTIs.

Methods: RPV RAMs were examined in plasma samples collected from HIV patients that had recently failed NNRTI-based regimens at 22 clinics in Spain.

Results: Resistance tests from a total of 1064 patients failing efavirenz (EFV) (54.5%), nevirapine (NVP) (40%) or etravirine (ETR) (5.5%) were examined. The prevalence of RPV RAMs was K101E (9.1%), K101P (1.4%), E138A (3.9%), E138G (0.3%), E138K (0.3%), E138Q (0.8%), V179L (0.2%), Y181C (21.8%), Y181I (0.5%), Y181V (0.2%), H221Y (8.3%), F227C (0.1%) and M230L (1.5%). K101E/M184I was seen in 1%. E138K/M184I were absent. Mutations L100I and V108I were significantly more frequent in patients failing EFV than NVP (7.9 vs. 0.2 and 12.2 vs. 7.3%, respectively). Conversely, Y181C, Y181I, V106A, H221Y and F227L were more prevalent following NVP than EFV failures. Using the Spanish resistance interpretation algorithm, 206 genotypes (19.3%) from patients failing NNRTI (NVP 52%, EFV 40.8% and ETR 7.8%) were considered as RPV resistant. In patients with ETR failure, cross-resistance to RPV was seen in 27.6%, mainly as result of Y181C (81.3%), V179I (43.8%), V90I (31.3%) and V108I (18.8%).

Conclusion: RPV resistance is overall recognized in nearly 20% of patients failing other NNRTIs. It is more common following ETR (27.6%) or NVP (25%) failures than EFV (14.5%). E138 mutants are rarely seen in this context.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Algorithms
  • Anti-HIV Agents / pharmacology
  • Anti-HIV Agents / therapeutic use*
  • Drug Resistance, Viral / genetics*
  • Female
  • Genotype
  • HIV Reverse Transcriptase / antagonists & inhibitors*
  • HIV Seropositivity / drug therapy*
  • HIV Seropositivity / genetics*
  • HIV-1 / drug effects*
  • HIV-1 / genetics
  • Humans
  • Male
  • Mutation
  • Nitriles / pharmacology
  • Nitriles / therapeutic use*
  • Nucleosides / therapeutic use
  • Pyrimidines / pharmacology
  • Pyrimidines / therapeutic use*
  • RNA, Viral / drug effects
  • Reverse Transcriptase Inhibitors / pharmacology
  • Reverse Transcriptase Inhibitors / therapeutic use*
  • Rilpivirine
  • Spain / epidemiology
  • Treatment Failure
  • Viral Load / drug effects

Substances

  • Anti-HIV Agents
  • Nitriles
  • Nucleosides
  • Pyrimidines
  • RNA, Viral
  • Reverse Transcriptase Inhibitors
  • HIV Reverse Transcriptase
  • Rilpivirine