Sequencing of protease inhibitor therapy: insights from an analysis of HIV phenotypic resistance in patients failing protease inhibitors

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Abstract
To characterize the pattern of HIV-1 susceptibility to protease inhibitors in patients failing an initial protease inhibitor-containing regimen. A cross-sectional analysis of antiretroviral susceptibility. HIV clinics in six metropolitan areas. Eighty-eight HIV-infected adults with HIV RNA > 400 copies/ml after ≥ 6 months of antiretroviral therapy, including the use of one protease inhibitor for ≥ 3 months. The frequency and magnitude of decreased susceptibility, measured with a phenotypic assay using recombinant constructs, to five protease inhibitors. Decreased susceptibility was defined as > 2.5-fold increase in the 50% inhibitory concentration (IC50) compared with drug sensitive control virus. At study entry, patients were being treated with nelfinavir (63%), indinavir (25%), or another protease inhibitor (11%). HIV isolates from these patients were susceptible (fold change P The frequency of protease inhibitor cross-resistance and the magnitude of changes in susceptibility varied according to the initial protease inhibitor used in the failing treatment regimen. Significantly less protease inhibitor cross-resistance was demonstrated for isolates from patients failing a nelfinavir-containing regimen compared with those from patients receiving other protease inhibitors.