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Abstract
A two-year randomized controlled clinical trial in antiretroviral-naïve subjects using lopinavir/ritonavir (LPV/r) monotherapy after initial induction treatment compared to an efavirenz (EFV) 3-drug regimen (Study M03-613)
W. Cameron1, B. da Silva2, J. Arribas3, R. Myers4, N. Bellos5, N. Gilmore6, K. Niemi2, K. Wikstrom2, M. King2, G. Hanna2, S. Brun2
1University of Ottawa at the Ottawa Hospital, Ottawa, Canada, 2Abbott Laboratories, Abbott Park, United States, 3Hospital La Paz, Madrid, Spain, 4Body Positive Inc., Phoenix, United States, 5Southwest Infectious Disease Associates, Dallas, United States, 6McGill University Health Center, Montreal, Canada
Background: With robust pharmacokinetics, high potency and high genetic barrier to resistance, LPV/r is a good candidate for evaluation as monotherapy for HIV infection.
Methods: 155 antiretroviral-naive HIV-1+ subjects were randomized 2:1 to LPV/r + zidovudine (ZDV) + lamivudine (3TC) induction (n=104) for at least 24 weeks followed by maintenance LPV/r monotherapy after 3 consecutive monthly viral loads (VL) <50 copies/mL, or to EFV+ZDV+3TC (n=51). The primary endpoint was the proportion achieving and maintaining VL <50 copies/mL through 96 weeks.
Results: Baseline characteristics were similar between arms. 92 (88%) of 104 LPV/r subjects started monotherapy. 79 LPV/r (69/92 on monotherapy) and 34 EFV-treated subjects completed the study. Drug-related discontinuations occurred in 3% of LPV/r-treated and 2% of EFV-treated subjects. In the primary analysis, 50% of LPV/r-treated and 61% of EFV treated subjects achieved and maintained VL <50 copies/mL through 96 weeks (intent-to-treat, previous failure=failure, p=0.23). By Kaplan-Meier analysis, the proportions maintaining VL <50, and <500 copies/mL through 72 weeks on LPV/r after deintensification were 62% and 84% respectively. Corresponding Kaplan-Meier estimates for EFV subjects after 3 consecutive VL <50 copies/mL were 91% <50 (p=0.002 vs. LPV/r monotherapy) and 95% <500 copies/mL (p=0.10 vs. LPV/r monotherapy). LPV/r monotherapy subjects with VL rebound to 50-500 copies/mL generally demonstrated viral resuppression to <50 copies/mL while continuing LPV/r monotherapy (11/12) or with resumption of NRTIs (2/4). New PI resistance mutations were detected in 2/15 (13%) LPV/r-treated subjects, while NNRTI resistance mutations were detected in 1/5 (20%) EFV-treated subjects (p>0.9).
Conclusions: After successful induction treatment with LPV/r+ZDV+3TC, LPV/r monotherapy continuously maintained VL suppression in a majority of subjects. LPV/r monotherapy had more intermittent VL increases between 50 and 500 copies/mL versus EFV+ZDV+3TC, but most subjects returned to <50 copies/mL. LPV/r monotherapy may be effective in selected patients.
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