TY - JOUR
T1 - Concentration-controlled compared with conventional antiretroviral therapy for HIV infection
AU - Fletcher, Courtney V.
AU - Anderson, Peter L.
AU - Kakuda, Thomas N.
AU - Schacker, Timothy W.
AU - Henry, Keith
AU - Gross, Cynthia R.
AU - Brundage, Richard C.
PY - 2002/3/8
Y1 - 2002/3/8
N2 - 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.
AB - 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.
KW - Antiretroviral therapy
KW - Combination therapy
KW - Drug concentrations
KW - Pharmacokinetics
KW - Therapeutic drug monitoring
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U2 - 10.1097/00002030-200203080-00006
DO - 10.1097/00002030-200203080-00006
M3 - Article
C2 - 11872998
AN - SCOPUS:0037040358
SN - 0269-9370
VL - 16
SP - 551
EP - 560
JO - AIDS
JF - AIDS
IS - 4
ER -