MaxCMin2 trial shows lopinavir/ritonavir superior to saquinavir/ritonavir

Keith Alcorn
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This article is more than 21 years old.

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.

Glossary

naive

In HIV, an individual who is ‘treatment naive’ has never taken anti-HIV treatment before.

p-value

The result of a statistical test which tells us whether the results of a study are likely to be due to chance and would not be confirmed if the study was repeated. All p-values are between 0 and 1; the most reliable studies have p-values very close to 0. A p-value of 0.001 means that there is a 1 in 1000 probability that the results are due to chance and do not reflect a real difference. A p-value of 0.05 means there is a 1 in 20 probability that the results are due to chance. When a p-value is 0.05 or below, the result is considered to be ‘statistically significant’. Confidence intervals give similar information to p-values but are easier to interpret. 

intent to treat analysis

All participants in a clinical trial are included in the final analysis, in the groups they were originally assigned to, whether or not they actually completed their course of treatment. This method provides a better estimate of the real-world effect of a treatment than an ‘on treatment’ analysis.

treatment-naive

A person who has never taken treatment for a condition.

loss to follow up

In a research study, participants who drop out before the end of the study. In routine clinical care, patients who do not attend medical appointments and who cannot be contacted.

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.

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