Secondary mutations in the protease region of human immunodeficiency virusand virologic failure in drug-naive patients treated with protease inhibitor-based therapy

The role of mutations in protease (PR) and reverse-transcriptase (RT) of hu man immunodeficiency virus (HIV) in predicting virologic failure was assess ed in 248 antiretroviral-naive HIV-positive patients who began a PR inhibit or-containing antiretroviral regimen. Genotypic testing was performed on pl asma samples stored before the start of therapy. Twenty-seven patients (10. 9%) had mutations in the RT, 5 (2%) carried primary mutations in the PR, an d 131 (52.8%) showed only secondary PR mutations. Virologic failure at week 24 occurred in 62 (25.0%) of 248 patients. There was a statistically signi ficant correlation between virologic failure and the number of PR mutations (P = .04, chi (2) test). Mutations at codons 10 and 36 of PR (present in 3 9.3% and 40.0% of patients in whom treatment failed, respectively) were ide ntified by stepwise logistic regression as the strongest predictors of viro logic failure (odds ratio, 2.20; 95% confidence interval, 1.30-3.75; P = .0 04). If confirmed in independent studies, this result may justify the incre ased use of HIV genotyping in drug-naive patients requiring antiretroviral therapy.