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  • Title: Plasma raltegravir exposure influences the antiviral activity and selection of resistance mutations.
    Author: Garrido C, de Mendoza C, Alvarez E, García F, Morello J, Garcia S, Ribera E, Rodríguez-Novoa S, Gutierrez F, Soriano V, Sinres Team.
    Journal: AIDS Res Hum Retroviruses; 2012 Feb; 28(2):156-64. PubMed ID: 21457126.
    Abstract:
    Raltegravir (RAL) resistance is associated with the selection of integrase mutations at positions 92, 143, 148, and/or 155. A substantial proportion of RAL failures, however, occurs in the absence of these changes. An examination of RAL plasma concentrations may help in interpreting this observation. All early RAL virological failures seen at 22 clinics in Spain during 2009 were identified. HIV integrase sequences and RAL plasma trough concentrations (C(t)) were examined. A total of 106 patients experiencing virological failure on RAL were identified. Only the earliest sample on failure was examined. Integrase sequences could be obtained for 89 (84%), of whom 30 (33.7%) depicted primary RAL resistance mutations (15 N155H, eight Q148H/R, three Y143R, one E92Q, and three more than one of them). Another nine (10.1%) patients showed only secondary changes. The remaining 50 RAL early failures (56.2%) did not select any integrase change. RAL C(t) could be measured in 66 patients at failure and in 21 of them before failure. In a control group of 37 patients with viral suppression on RAL, detectable plasma levels were seen in all cases, with greater median RAL C(t) than in failures, either at the time of viral rebound (p<0.001) or before it (p=0.055). Moreover, median C(t) at the time of failure was greater in patients selecting primary RAL resistance mutations than in the rest of the failures (p<0.001). Undetectable RAL C(t) was seen only in patients failing RAL without integrase resistance mutations (64.1% of them). RAL failures in the absence of integrase resistance mutations mainly reflect poor drug compliance.
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