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

48 Citations (Scopus)

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
Externally publishedYes

Fingerprint

Integrase Inhibitors
Integrases
HIV
Therapeutics
CD4 Lymphocyte Count
Drug Resistance
RNA
T-Lymphocytes
Pharmaceutical Preparations

Keywords

  • drug resistance
  • integrase inhibitors
  • virologic failure

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Infectious Diseases

Cite this

Evolution of integrase resistance during failure of integrase inhibitor-based antiretroviral therapy. / Hatano, Hiroyu; Lampiris, Harry; Fransen, Signe; Gupta, Soumi; Huang, Wei; Hoh, Rebecca; Martin, Jeffrey N.; Lalezari, Jacob; Bangsberg, David; Petropoulos, Christos; Deeks, Steven G.

In: Journal of Acquired Immune Deficiency Syndromes, Vol. 54, No. 4, 01.08.2010, p. 389-393.

Research output: Contribution to journalArticle

Hatano, H, Lampiris, H, Fransen, S, Gupta, S, Huang, W, Hoh, R, Martin, JN, Lalezari, J, Bangsberg, D, Petropoulos, C & Deeks, SG 2010, 'Evolution of integrase resistance during failure of integrase inhibitor-based antiretroviral therapy', Journal of Acquired Immune Deficiency Syndromes, vol. 54, no. 4, pp. 389-393. https://doi.org/10.1097/QAI.0b013e3181c42ea4
Hatano, Hiroyu ; Lampiris, Harry ; Fransen, Signe ; Gupta, Soumi ; Huang, Wei ; Hoh, Rebecca ; Martin, Jeffrey N. ; Lalezari, Jacob ; Bangsberg, David ; Petropoulos, Christos ; Deeks, Steven G. / Evolution of integrase resistance during failure of integrase inhibitor-based antiretroviral therapy. In: Journal of Acquired Immune Deficiency Syndromes. 2010 ; Vol. 54, No. 4. pp. 389-393.
@article{1b9c2bf588d14ae4bc825dc50c180af6,
title = "Evolution of integrase resistance during failure of integrase inhibitor-based antiretroviral therapy",
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.",
keywords = "drug resistance, integrase inhibitors, virologic failure",
author = "Hiroyu Hatano and Harry Lampiris and Signe Fransen and Soumi Gupta and Wei Huang and Rebecca Hoh and Martin, {Jeffrey N.} and Jacob Lalezari and David Bangsberg and Christos Petropoulos and Deeks, {Steven G.}",
year = "2010",
month = "8",
day = "1",
doi = "10.1097/QAI.0b013e3181c42ea4",
language = "English (US)",
volume = "54",
pages = "389--393",
journal = "Journal of Acquired Immune Deficiency Syndromes",
issn = "1525-4135",
publisher = "Lippincott Williams and Wilkins",
number = "4",

}

TY - JOUR

T1 - Evolution of integrase resistance during failure of integrase inhibitor-based antiretroviral therapy

AU - Hatano, Hiroyu

AU - Lampiris, Harry

AU - Fransen, Signe

AU - Gupta, Soumi

AU - Huang, Wei

AU - Hoh, Rebecca

AU - Martin, Jeffrey N.

AU - Lalezari, Jacob

AU - Bangsberg, David

AU - Petropoulos, Christos

AU - Deeks, Steven G.

PY - 2010/8/1

Y1 - 2010/8/1

N2 - 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.

AB - 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.

KW - drug resistance

KW - integrase inhibitors

KW - virologic failure

UR - http://www.scopus.com/inward/record.url?scp=77955504896&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77955504896&partnerID=8YFLogxK

U2 - 10.1097/QAI.0b013e3181c42ea4

DO - 10.1097/QAI.0b013e3181c42ea4

M3 - Article

VL - 54

SP - 389

EP - 393

JO - Journal of Acquired Immune Deficiency Syndromes

JF - Journal of Acquired Immune Deficiency Syndromes

SN - 1525-4135

IS - 4

ER -