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

Montaner, Julio S. G.a,b,c; Harrigan, P. Richarda; Jahnke, Nataliea; Raboud, Janetc,d; Castillo, Elianaa; Hogg, Robert S.a,d; Yip, Benitaa; Harris, Mariannea; Montessori, Vala,b; O'Shaughnessy, Michael V.a,c,e

Clinical Science

Objectives To characterize the antiviral response and tolerability of a multi-drug rescue therapy (MDRT) among heavily pretreated patients.

Methods Observational 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.

Results Median 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.

Conclusion MDRT 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.

From the aBritish Columbia Centre for Excellence in HIV/AIDS, St. Paul's Hospital, the bDepartment of Medicine, Faculty of Medicine, University of British Columbia, the cCanadian HIV Trials Network; Vancouver, British Columbia, and the Departments of dHealth Care and Epidemiology and ePathology, Faculty of Medicine, University of British Columbia; Canada.

Received: 27 March 2000;

revised: 13 September 2000; accepted: 20 October 2000.

Sponsorship: Supported by the National Health Research Development Program of the Department of National Health and Welfare of Canada through National Health Research Scholar Awards to J. S. G. Montaner and R. S. Hogg. Partial financial support was provided by Bristol Myers Squibb Canada.

Requests for reprints to: J. S. G. Montaner, Director, AIDS Research Program, St. Paul's Hospital, 667-1081 Burrard Street, Vancouver, BC V6Z 1Y6, Canada.

© 2001 Lippincott Williams & Wilkins, Inc.