MaxCMin2 trial shows lopinavir/ritonavir superior to saquinavir/ritonavir

MaxCMin2, a large European randomised comparison of lopinavir/ritonavir and saquinavir/ritonavir has shown that lopinavir/ritonavir is superior to ritonavir/saquinavir over 48 weeks of follow-up. The results of the study were presented as a late breaker on the final day of the Second International AIDS Society Conference on HIV Pathogenesis and Treatment in Paris.

MaxCMin2 recruited 324 treatment-naive and treatment-experienced patients in Europe and Canada, and compared lopinavir/ritonavir 400/100mg with saquinavir/ritonavir 1000/100mg, both taken twice daily. All patients took at least two nucleoside analogues. 33% were antiretroviral-naïve, 48% were protease inhibitor-naïve, and 32% had experienced virologic failure of at least one protease inhibitor. 21% had experienced intolerance of at least one protease inhibitor.

The median baseline CD4 cell count of patients in the study was 240 cells/mm³.

The final 48 week analysis included complete follow-up data on 304 of the 324 patients who initiated the assigned treatment, and showed that after 48 weeks:

• The risk of virologic failure was higher in the saquinavir/ritonavir arm than the lopinavir/ritonavir arm by intent to treat analysis (p=0.0009).

The risk of treatment discontinuation was also higher in saquinavir arm (29% vs 13%, p=0.0001)

Discontinuation was due to adverse events in 20 saquinavir-treated patients and 13 lopinavir-treated patients. However, there was no overall difference in the risk of grade 3 and 4 adverse events in the two arms.

Other discontinuations were due to patient choice or non-adherence (5 LPV, 14 SQV treated patients), loss to follow up, death and other causes. Only three discontinuations were due to virologic failure (in the SQV arm).

A significantly larger number of saquinavir-treated patients developed category B or C opportunistic illnesses during the study (17, vs 6 in the LPV arm, p=0.03).

The heterogenous population and incomplete analysis makes it difficult to draw clearcut conclusions from this study. Unanswered questions include:

• Superiority of one drug over another in treatment-naïve or PI-experienced patients

Lipid changes in the populations treated

Nature of the adverse events causing discontinuation

References

Youle M et al. The final week 48 analysis of a phase IV randomised open label multicentre trial to evaluate safety and efficacy of lopinavir/ritonavir (400/100mg) vs saquinavir/ritonavir (1000/100mg bid) in adult HIV-1 infection: the MaxCMin2 study. Second International AIDS Society Conference on HIV Pathogenesis and Treatment, Paris, abstract LB23, 2003.