Extent and importance of cross-resistance to efavirenz after XXXX failure.

@entity1 @entity645 @entity19898 @entity5198 @entity24606
The objective of this study was to evaluate the activity of efavirenz after the failure of a @entity5198 -containing regimen. This prospective study included 47 @entity1 with plasma @entity645 loads >1000 copies/ml, and who had received @entity5198 for at least 16 weeks, included in an efavirenz-based salvage regimen. The main outcome measure was virological response, defined as an @entity645 RNA level decrease of at least 1 log(10) copies/ml after 24 weeks, according to genotypic and phenotypic resistance to efavirenz. Phenotypic resistance was defined as a >10-fold increase in the IC(50). The median CD4(+) cell count was 236 x 10(6)/liter and the median @entity645 RNA level was 4.5 log(10) copies/ml. Mutations known to decrease susceptibility to nonnucleoside reverse transcriptase inhibitors were observed in 79% of @entity1 , predominantly at residues 181 (49%), 103 (40%), and 106 (19%), but phenotypic resistance to efavirenz was seen in 62% of cases. All the strains with the @entity19898 mutation showed high-level resistance to efavirenz, in contrast with 20% of those carrying exclusively the @entity24606 mutation. By week 24, 38% of @entity1 had responded and 19% had achieved an undetectable @entity645 load. Virological failure was observed in @entity1 with phenotypic resistance to efavirenz (67 vs. 11%; relative risk [RR], 4; 95% confidence interval [CI], 1.07-14.89; p = 0.04), or in presence of the @entity19898 mutation (52 vs. 17%; RR, 1.77; 95% CI, 1.12-2.79; p = 0.02), and these results remained unchanged after adjusting for @entity645 load, or by resistance to the accompanying drugs in the salvage regimen. A previous longer period of @entity5198 therapy was significantly associated with the emergence of efavirenz resistance (288 vs. 170 days, p < 0.01). We conclude that genotypic and/or phenotypic resistance assays permit the sequential use of nonnucleoside reverse transcriptase inhibitors in the clinical setting. Our data suggest that an early change after @entity5198 failure could avoid the emergence of efavirenz resistance.
