This review discusses how “virtual” and conventional phenotypic assays establish clinical cutoffs predictive of response in HIV isolates from antiretroviral-experienced patients. Sophisticated phenotypic assays that incorporate linear regression modeling and conventional phenotypic assays have been used to define and validate clinical cutoffs (i.e. the correlation between viral susceptibility and treatment response) for most antiretrovirals, including the newer protease inhibitors. Using these clinical cutoff values, clinical data show that the newer protease inhibitors retain activity against the majority of isolates from treatment-experienced patients and from those with baseline resistance to multiple protease inhibitors. The utility of phenotypic resistance testing methods have therefore been validated in the clinical setting. In summary, HIV drug resistance testing is currently the recommended standard of care for the selection of antiretroviral regimens for HIV-infected patients in multiple clinical settings. An understanding of the basic principles of phenotypic resistance testing is crucial for providing optimal care, particularly for antiretroviral-experienced patients.

(AIDS Rev. 2009;11: 223-30) Corresponding author: Rodger D. MacArthur, rmacarthur@med.wayne.edu