ObjectivesTo characterize the antiviral response and tolerability of a multi-drug rescue therapy (MDRT) among heavily pretreated patients.MethodsObservational study conducted in a single, university-based tertiary referral clinic. Patients (n = 106) who failed several prior regimens started MDRT including at least five antiretroviral (ARV) drugs between August 1997 and June 1998. The most common starting regimen included three nucleoside reverse transcriptase inhibitors and two protease inhibitors, which was prescribed to 45 (42.5%) patients. Virologic response was defined as plasma viral load < 400 copies/ml on at least two consecutive visits.ResultsMedian prior ARV exposure was seven drugs over a median time of 43 months. Fifty-nine percent of the patients were phenotypically (VIRCO Antivirogram) resistant at baseline to seven or more ARV. Median plasma viral load change following initiation of MDRT was −1.04 log10 copies/ml over a median of 15 months. Using intention-to-treat analysis 40% of patients had plasma viral load values < 400 copies/ml between weeks 47 and 57 of follow-up. Twenty-six patients (25%) experienced severe laboratory abnormalities or subjective adverse drug effects and six of these participants discontinued therapy.ConclusionMDRT induced a substantial antiviral response in this heavily pretreated group of patients despite extensive phenotypic resistance at baseline. Adverse effects were frequent but generally manageable. Our data suggest that relying exclusively on historical, clinical and laboratory evidence may not be sufficient to rule out a possible antiviral response when multiple drug regimens are used in this heavily pretreated patient population.