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Therapy with atazanavir plus saquinavir in patients failing highly active antiretroviral therapy: a randomized comparative pilot trial

Haas, David Wa,b; Zala, Carlosc; Schrader, Shannond; Piliero, Petere; Jaeger, Hansf; Nunes, Danilog; Thiry, Alexandrah; Schnittman, Stevenh; Sension, Michaeli; for the Protocol AI424-009 Study Group

Clinical Science

Objectives: To assess the safety, efficacy of atazanavir (400 and 600 mg)/saquinavir (1200 mg) once daily versus ritonavir/saquinavir (400 mg/400 mg) twice daily with two nucleoside reverse transcriptase inhibitors (NRTIs) in highly active antiretroviral therapy failure.

Design and methods: Randomized, multinational, 48-week, pilot trial with antiretroviral-experienced patients having at least 1000 HIV-1 RNA copies/ml, 100 × 106 CD4 cells/l (75 × 106 cells/l without AIDS diagnosis) and virological response to a prior regimen. Efficacy was evaluated by HIV-1 RNA and CD4 cell changes from baseline to 48 weeks.

Results: Comparable efficacy across groups at 48 weeks: mean HIV-1 RNA decreases, 1.44, 1.19 and 1.66 log10 copies/ml (P = NS) and comparable virological response (> 1.0 log10 decrease HIV-1 RNA or HIV-1 RNA < 400 copies/ml) was achieved in 41, 29 and 35% (P = NS); and mean CD4 cell increases, 109, 55 and 149 × 106 cells/l in atazanavir 400-mg, atazanavir 600-mg and ritonavir groups, respectively. There were fewer adverse event discontinuations in the atazanavir groups (9%, 11%) versus the ritonavir group (30%) and atazanavir lacked adverse effects on lipids. In the atazanavir 400-mg, atazanavir 600-mg and ritonavir groups the mean changes from baseline at 48 weeks in fasting low-density lipoprotein (LDL) cholesterol concentrations were −0.6, −6.7 and 23.2%, respectively and in fasting triglyceride concentrations they were −4.8, −27.1 and 93.0%, respectively (P < 0.05, LDL cholesterol; P < 0.001, fasting triglyceride; atazanavir/saquinavir versus ritonavir/saquinavir).

Conclusions: In antiretroviral-experienced patients, once-daily atazanavir/saquinavir was safe and well tolerated, showing comparable efficacy to twice-daily ritonavir/saquinavir, both with two NRTIs. Small lipid changes from baseline with atazanavir/saquinavir were not clinically significant in comparison with the prompt, marked and sustained changes of a magnitude suggesting clinical relevance achieved in the ritonavir/saquinavir group.

From the aVanderbilt University School of Medicine, Nashville, Tennessee, the bComprehensive Care Center, Nashville, Tennessee, USA, the cFundacion Huesped and Department of Microbiology, School of Medicine, University of Buenos Aires, Argentina, the dHCRN/Montrose Clinic, Houston, Texas, the eAlbany Medical College, Albany, New York, the fMUC Research, Inc., Munich, Germany, the gInstituto De Infectologia Emilio Ribas, Sao Paulo, Brazil, the hBristol-Myers Squibb Company, Wallingford, Connecticut and the iNorth Broward Hospital, Ft. Lauderdale, Florida, USA.

Correspondence to David W. Haas, MD, Associate Professor of Medicine, Division of Infectious Diseases, Vanderbilt University School of Medicine, 345 24th Ave North, Suite 105, Nashville, TN 37212, USA. Tel: +1 615 467 0154; fax: +1 615 467 0158; e-mail: david.w.haas@vanderbilt.edu

Received: 9 August 2002; revised: 19 December 2002; accepted: 22 january 2003.

© 2003 Lippincott Williams & Wilkins, Inc.