OBJECTIVES: To demonstrate the feasibility of a concentration-controlled approach to combination antiretroviral therapy, and to compare the virological responses and safety of this strategy versus conventional fixed-dose therapy. DESIGN: A prospective, randomized, 52 week, open-label trial of concentration-controlled compared with conventional dose zidovudine, lamivudine, and indinavir therapy conducedin a university-based general clinical research center in the United States. PATIENTS: Forty antiretroviral-naive individuals with plasma HIV-RNA levels > 5000 copies/ml. INTERVENTIONS:Zidovudine, lamivudine, and indinavir plasma concentrations were measured in all participants. Doses were adjusted in those assigned to concentration-controlled therapy to achieve levels equal to or greater than target values. MAIN OUTCOME MEASURES: The proportion of patients who achieved the desired drug concentrations, the proportion of patients with HIV-RNA levels < 50 copies/ml at week 52, and safety and tolerance in the concentration-controlled versus conventional therapy arms. RESULTS: Significantly more concentration-controlled recipients achieved the desired concentration targets for all three drugs: 15 of 16 concentration-controlled recipients compared with nine of 17 conventional recipients (P = 0.017) had HIV-RNA levels < 50 copies/ml at week 52. No difference was observed in the occurrence of drug-related clinical events or laboratory abnormalities between the two treatment arms. CONCLUSION: Concentration-controlled therapy implemented simultaneously for three antiretroviral agents was feasible, as well tolerated as conventional therapy, and resulted in a greater proportion of recipients with HIV-RNA levels < 50 copies/ml after 52 weeks. These findings provide a scientific basis to challenge the accepted practice of administering the same dose of antiretroviral agents to all adults, ignoring the concentrations actually achieved.
RCT Entities:
OBJECTIVES: To demonstrate the feasibility of a concentration-controlled approach to combination antiretroviral therapy, and to compare the virological responses and safety of this strategy versus conventional fixed-dose therapy. DESIGN: A prospective, randomized, 52 week, open-label trial of concentration-controlled compared with conventional dose zidovudine, lamivudine, and indinavir therapy conduced in a university-based general clinical research center in the United States. PATIENTS: Forty antiretroviral-naive individuals with plasma HIV-RNA levels > 5000 copies/ml. INTERVENTIONS:Zidovudine, lamivudine, and indinavir plasma concentrations were measured in all participants. Doses were adjusted in those assigned to concentration-controlled therapy to achieve levels equal to or greater than target values. MAIN OUTCOME MEASURES: The proportion of patients who achieved the desired drug concentrations, the proportion of patients with HIV-RNA levels < 50 copies/ml at week 52, and safety and tolerance in the concentration-controlled versus conventional therapy arms. RESULTS: Significantly more concentration-controlled recipients achieved the desired concentration targets for all three drugs: 15 of 16 concentration-controlled recipients compared with nine of 17 conventional recipients (P = 0.017) had HIV-RNA levels < 50 copies/ml at week 52. No difference was observed in the occurrence of drug-related clinical events or laboratory abnormalities between the two treatment arms. CONCLUSION: Concentration-controlled therapy implemented simultaneously for three antiretroviral agents was feasible, as well tolerated as conventional therapy, and resulted in a greater proportion of recipients with HIV-RNA levels < 50 copies/ml after 52 weeks. These findings provide a scientific basis to challenge the accepted practice of administering the same dose of antiretroviral agents to all adults, ignoring the concentrations actually achieved.
Authors: Rutao Luo; Lamont Cannon; Jason Hernandez; Michael J Piovoso; Ryan Zurakowski Journal: J Process Control Date: 2011-03-01 Impact factor: 3.666
Authors: Alice Tseng; Michelle Foisy; Christine A Hughes; Deborah Kelly; Shanna Chan; Natalie Dayneka; Pierre Giguère; Niamh Higgins; Cara Hills-Nieminen; Jeff Kapler; Charles J L la Porte; Pam Nickel; Laura Park-Wyllie; Carlo Quaia; Linda Robinson; Nancy Sheehan; Shannon Stone; Linda Sulz; Deborah Yoong Journal: Can J Hosp Pharm Date: 2012-03