Evolution of integrase resistance during failure of integrase inhibitor-based antiretroviral therapy

Hiroyu Hatano, Harry Lampiris, Signe Fransen, Soumi Gupta, Wei Huang, Rebecca Hoh, Jeffrey N. Martin, Jacob Lalezari, David Bangsberg, Christos Petropoulos, Steven G. Deeks

Research output: Contribution to journalArticle

49 Scopus citations

Abstract

Background: Although integrase inhibitors are highly effective in the management of drug-resistant HIV, some patients fail to achieve durable viral suppression. The long-term consequences of integrase inhibitor failure have not been well defined. Methods: We identified 29 individuals who exhibited evidence of incomplete viral suppression on a regimen containing an integrase inhibitor (23 raltegravir, 6 elvitegravir). Before initiating the integrase inhibitor-based regimen, the median CD4 T-cell count and plasma HIV RNA levels were 62 cells/mm and 4.65 log10 copies/mL, respectively. Results: At the first failure time-point, the most common integrase resistance pattern for subjects taking raltegravir was wild-type, followed in order of frequency by Q148H/K/R+G140S, N155H, and Y143R/H/C. The most common resistance pattern for subjects taking elvitegravir was E92Q. Long-term failure was associated with continued viral evolution, emergence of high-level phenotypic resistance, and a decrease in replicative capacity. Conclusions: Although wild-type failure during early integrase inhibitor failure is common, most patients eventually develop high-level phenotypic drug resistance. This resistance evolution is gradual and associated with declines in replicative capacity.

Original languageEnglish (US)
Pages (from-to)389-393
Number of pages5
JournalJournal of Acquired Immune Deficiency Syndromes
Volume54
Issue number4
DOIs
StatePublished - Aug 1 2010

Keywords

  • drug resistance
  • integrase inhibitors
  • virologic failure

ASJC Scopus subject areas

  • Infectious Diseases
  • Pharmacology (medical)

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    Hatano, H., Lampiris, H., Fransen, S., Gupta, S., Huang, W., Hoh, R., Martin, J. N., Lalezari, J., Bangsberg, D., Petropoulos, C., & Deeks, S. G. (2010). Evolution of integrase resistance during failure of integrase inhibitor-based antiretroviral therapy. Journal of Acquired Immune Deficiency Syndromes, 54(4), 389-393. https://doi.org/10.1097/QAI.0b013e3181c42ea4