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Evolution of Integrase Resistance During Failure of Integrase Inhibitor-Based Antiretroviral Therapy

2010; Lippincott Williams & Wilkins; Volume: 54; Issue: 4 Linguagem: Inglês

10.1097/qai.0b013e3181c42ea4

1944-7884

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

Biochemical and Molecular Research

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.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.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.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.