[LB23] THE FINAL WEEK 48 ANALYSIS OF A PHASE IV, RANDOMISED, OPEN-LABEL, MULTI-CENTRE TRIAL TO EVALUATE SAFETY AND EFFICACY OF LOPINAVIR/RITONAVIR (400/100 MG BID) VERSUS SAQUINAVIR/RITONAVIR (1000/100 MG BID) IN ADULT HIV-1 INFECTION: THE MAXCMIN2 TRIAL

2nd International AIDS Society Conference on HIV Pathogenesis and Treatment

Paris, France - July 13 - 16, 2003

[TITLE:] THE FINAL WEEK 48 ANALYSIS OF A PHASE IV, RANDOMISED, OPEN-LABEL, MULTI-CENTRE TRIAL TO EVALUATE SAFETY AND EFFICACY OF LOPINAVIR/RITONAVIR (400/100 MG BID) VERSUS SAQUINAVIR/RITONAVIR (1000/100 MG BID) IN ADULT HIV-1 INFECTION: THE MAXCMIN2 TRIAL

[AUTHOR(S):] M. Youle, J. Gerstoft, Z. Fox, M. Losso, D.T. Jayaweera, A. Rieger, J.N. Bruun, A. Castagna, S. Walmsley, A. Hill, U.B. Dragsted, J.D. Lundgren for MaxCmin2 trial group
Copenhagen HIV Programme (CHIP), Hvidovre University Hospital, Denmark

IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd: Abstract No. LB23

[ABSTRACT:] The primary objective of the trial is to compare the rate of virological failure at 48 weeks for the lopinavir/r (LPV/r) arm relative to the saquinavir/r (SAQ/r) arm. Also, to compare the proportion of patients with HIV-1 RNA < 50 c/ml at week 48, discontinuation of the randomised (R-) treatment (tx), and safety. The trial is randomised (1:1), phase IV, open-label, and multi-centre. Concomitant use of = 2 NRTI/NNRTI was decided prior to randomisation. Analyses are intention-to-treat on patients exposed to the R-tx (ITT/e (switch included) and ITT/e/switch = failure) and on treatment (OT). All patients, whether discontinued or on the R-tx, were followed for 48 weeks. The R-Tx was initiated in 324/339 (96 %) randomised patients of whom complete follow-up data is available from 304 (94 %). Patients were primarily male (79 %) homosexuals (45 %), PI-experienced (52 %); 33 % were ART-naïve. The risk of protocol-defined virological failure was higher in the SAQ/r arm compared to the LPV/r arm in the ITT/e (p = 0.0009, log rank test) and the ITT/e/s (p = 0.002) analyses, but not in the OT (p = 0.14) analysis. Further, at week 48, 64 % vs. 56 % (ITT/e), 60 % vs. 52 % (ITT/e/s), and 70 % vs. 75 % (OT) in the LPV/r and SAQ/r arm, respectively, had a HIV-RNA < 50 copies/ml (p > 0.05 for all comparisons). Discontinuation of the R-Tx occurred in 69/324 (21 %) patients, 13 % in the LPV/r vs. 29 % in the SAQ/r arm (p = 0.001). In 48 % discontinuation was due to a non-fatal adverse event (AE). No difference in risk of grade 3 and/or 4 AEs was seen between the two arms. In this well balanced but heterogeneous population more patients in the SAQ/r arm experienced protocol-defined virological failure as compared to the LPV/r arm. This difference was not observed in the on-treatment analysis. The clinical toxicity profile was comparable between the two arms, but more patients discontinued SAQ/r due to patients' choice.

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