Different methods to calculate the inhibitory quotient of boosted single protease inhibitors and their association with virological response.

In individuals with incomplete suppression of HIV replication, a major clinical challenge is to establish which agents retain significant antiviral activity. Measurements of both plasma concentration and resistance of selected antiretro-viral agents are widely available. Clinical studies have shown short-term virologic benefit associated with the use of resistance testing in drug-experienced patients; however , no clinical benefit has been observed with the use of plasma drug concentration monitoring in treated individuals. 1 Inhibitory quotient (IQ), a measure of plasma drug exposure corrected by the degree of resistance, may enhance the result of HIV resistance tests by correcting for plasma drug exposure. Several methods to calculate IQ have been proposed including genotypic IQ (GIQ), virtual IQ (VIQ), and normalized IQ (NIQ), where the ratio of plasma drug exposure to a measure of genotypic resistance, virtual phenotypic resistance, or a calculated population IQ are calculated , respectively. Significant associations have been described between virologic response and the GIQ, VIQ, and NIQ. 2Y6 Despite these studies, there is a lack of standardization in the calculation of IQ, and there are no data on the benefit of 1 calculation compared with another which limits their use in clinical practice. The aim of this study was to assess the association between virologic response in a cohort of HIV-1 treatment-experienced patients changing antiretro-viral therapy because of virologic failure or intolerance within a prospective cohort and a range of covariates including the GIQ, VIQ, and NIQ. The Therapeutic Drug Monitoring (TDM) Study is an ongoing prospective study assessing the usefulness of measuring protease inhibitor (PI) and nonnucleo-side reverse transcriptase inhibitor trough plasma concentrations (C trough) in HIV-1 positive patients commencing new anti-retroviral regimens at the Chelsea and Westminster Hospital, London, United Kingdom. Subjects recruited for the study underwent blood sampling to assess plasma PI and nonnucleoside reverse transcriptase inhibitor C trough at 4, 24, and 48 weeks. As part of a planned 24-week analysis, all antiretroviral-exposed subjects who had commenced a new ritonavir-boosted single PI regimen who enrolled in the TDM study were included in the current analysis. All subjects had an HIV resistance test before commencing antiretroviral therapy and when changing therapy because of virologic failure. For the purpose of this analysis, the most recent HIV resistance test within 6 weeks of changing antiretroviral therapy was used. Fold change (FC) for each PI was determined from the predicted FC virtual phenotype report. The C trough of …