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To examine effectiveness of subsequent antiretroviral therapy (ART), studies published during the period of 1 January 1997 through 31 May 2003 involving patients who had failed a protease inhibitor (PI)-containing regimen and were switched to another regimen were reviewed. Twelve studies describing 1197 patients were analyzed. A total of 38% of patients had human immunodeficiency virus (HIV) RNA levels of <500 copies/mL at 24 weeks. After adjustment for baseline HIV RNA level, the rate of virologic suppression ranged from 16% for patients switching drugs within previously failed classes to 54% for nonnucleoside reverse-transcriptase inhibitor (NNRTI)-naive patients switched to boosted PI- and NNRTI-containing regimens. ART regimens in patients who failed a PI-containing regimen provided virologic suppression only in a few patients. The best response was seen in NNRTI-naive patients receiving NNRTI- and boosted PI-containing regimens. New approaches are needed to achieve better suppression in pretreated HIV-infected patients.