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
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U2 - 10.1097/QAI.0b013e3181c42ea4
DO - 10.1097/QAI.0b013e3181c42ea4
M3 - Article
C2 - 20300008
AN - SCOPUS:77955504896
SN - 1525-4135
VL - 54
SP - 389
EP - 393
JO - Journal of Acquired Immune Deficiency Syndromes
JF - Journal of Acquired Immune Deficiency Syndromes
IS - 4
ER -