Multiple drug rescue therapy for HIV-infected individuals with prior virologic failure to multiple regimens

Objectives: To characterize the antiviral response and tolerability of a mu lti-drug rescue therapy (MDRT) among heavily pretreated patients. Methods: Observational study conducted in a single, university-based tertia ry referral clinic. Patients (n = 106) who failed several prior regimens st arted MDRT including at least five antiretroviral (ARV) drugs between Augus t 1997 and June 1998. The most common starting regimen included three nucle oside reverse transcriptase inhibitors and two protease inhibitors, which w as prescribed to 45 (42.5%) patients. Virologic response was defined as pla sma viral load < 400 copies/ml on at least two consecutive visits. Results: Median prior ARV exposure was seven drugs over a median time of 43 months. Fifty-nine percent of the patients were phenotypically (VIRCO Anti virogram) resistant at baseline to seven or more ARV. Median plasma viral l oad change following initiation of MDRT was -1.04 log(10) copies/ml over a median of 15 months. Using intention-to-treat analysis 40% of patients had plasma viral load values < 400 copies/ mi 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 discontinu ed therapy. Conclusion: MDRT induced a substantial antiviral response in this heavily p retreated group of patients despite extensive phenotypic resistance at base line. Adverse effects were frequent but generally manageable. Our data sugg est that relying exclusively on historical, clinical and laboratory evidenc e may not be sufficient to rule out a possible antiviral response when mult iple drug regimens are used in this heavily pretreated patient population. (C) 2001 Lippincott Williams & Wilkins.