Therapy with atazanavir plus saquinavir in patients failing highly active antiretroviral therapy: a randomized comparative pilot trial
- 1 June 2003
- journal article
- clinical trial
- Published by Ovid Technologies (Wolters Kluwer Health) in AIDS
- Vol. 17 (9), 1339-1349
- https://doi.org/10.1097/00002030-200306130-00008
Abstract
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. Randomized, multinational, 48-week, pilot trial with antiretroviral-experienced patients having at least 1000 HIV-1 RNA copies/ml, 100 x 106 CD4 cells/l (75 x 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. Comparable efficacy across groups at 48 weeks: mean HIV-1 RNA decreases, 1.44, 1.19 and 1.66 log(10) copies/ml (P = NS) and comparable virological response (> 1.0 log(10) 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 x 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). 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.Keywords
This publication has 21 references indexed in Scilit:
- Antiretroviral Therapy for Previously Treated PatientsNew England Journal of Medicine, 2001
- Multiple drug rescue therapy for HIV-infected individuals with prior virologic failure to multiple regimensAIDS, 2001
- ABT-378/ritonavir plus stavudine and lamivudine for the treatment of antiretroviral-naive adults with HIV-1 infection: 48-week resultsAIDS, 2001
- The use of and response to second-line protease inhibitor regimens: results from the EuroSIDA studyAIDS, 2001
- Safety and Pharmacokinetics of Once-Daily Regimens of Soft-Gel Capsule Saquinavir plus Minidose Ritonavir in Human Immunodeficiency Virus-Negative AdultsAntimicrobial Agents and Chemotherapy, 2000
- Strategies for long-term success in the treatment of HIV infection.JAMA, 2000
- HIV-1 Genotypic Resistance Patterns Predict Response to saquinavir–ritonavir Therapy in Patients in Whom Previous Protease Inhibitor Therapy Had FailedAnnals of Internal Medicine, 1999
- Clinical progression and virological failure on highly active antiretroviral therapy in HIV-1 patients: a prospective cohort studyThe Lancet, 1999
- Virologic responses to a ritonavir-saquinavir-containing regimen in patients who had previously failed nelfinavirAIDS, 1999
- Declining Morbidity and Mortality among Patients with Advanced Human Immunodeficiency Virus InfectionNew England Journal of Medicine, 1998