A randomized trial to evaluate lopinavir/ritonavir versus saquinavir/ritonavir in HIV-1-infected patients: the MaxCmin2 trial.
OBJECTIVE
To assess the rate of protocol-defined treatment failure and safety of lopinavir/ritonavir (LPV/r) and saquinavir/ritonavir (SAQ/r).


METHODS
Open-label, prospective, randomized (1:1), international multi-centre trial.


METHODS
Adult HIV-1-infected patients were assigned LPV/r 400/100 mg twice daily or SAQ/r 1000/100 mg twice daily with two or more nucleoside reverse transcriptase inhibitors (NRTIs)/non-NRTIs. All patients, whether on or off the assigned treatment, were followed for 48 weeks.


RESULTS
Of 339 randomized patients, 324 initiated assigned treatment (intention-to-treat/exposed [ITT/e] population). At 48 weeks, treatment failure occurred in 29/163 (18%) and 53/161 (33%) of patients in the LPV/r and SAQ/r arms, respectively (ITT/e, P = 0.002, log rank test). In an analysis that also considered those patients who discontinued treatment as having failed treatment (ITT/e/discontinuation = failure), 40/161 (25%) LPV/r-treated individuals versus 63/161 (39%) SAQ/R-treated individuals failed treatment (P = 0.005, log rank test). Discontinuation of the assigned treatment occurred in 23/163 (14%) patients in the LPV/r-treated group, compared with 48/161 (300%) in the SAQ/r-treated group (ITT/e; P = 0.001). The primary reasons for premature discontinuation were non-fatal adverse events (LPV/r: 12/163; SAQ/r: 21/161) and patients' choice (LPV/r: 7/163; SAQ/r: 8/161). In the on-treatment analysis of time to treatment failure, no difference was observed between the two arms (P = 0.27, log rank test).


CONCLUSIONS
LPV/r had better antiretroviral effects compared with SAQ/r at the doses and in the formulations studied. This may have been a result of patients' preferences and ability to adhere to assigned therapy, rather than a result of differences in the intrinsic potency of the study protease inhibitors.
Dragsted
Ulrik B
UB
Hvidovre University Hospital, Copenhagen, Denmark. ubd@cphiv.dk
Gerstoft
Jan
J
Youle
Mike
M
Fox
Zoe
Z
Losso
Marcello
M
Benetucci
Jorge
J
Jayaweera
Dushyantha T
DT
Rieger
Armin
A
Bruun
Johan N
JN
Castagna
Antonella
A
Gazzard
Brian
B
Walmsley
Sharon
S
Hill
Andrew
A
Lundgren
Jens D
JD
D000328:Adult; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D061466:Lopinavir; D008297:Male; D008875:Middle Aged; D011744:Pyrimidinones / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D019438:Ritonavir / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D019258:Saquinavir / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D016896:Treatment Outcome
D017320:HIV Protease Inhibitors; D011744:Pyrimidinones; D061466:Lopinavir; D019258:Saquinavir; D019438:Ritonavir