Saquinavir/r vs lopinavir/r: interim results from the Gemini study

Results were presented in Glasgow by Slim and colleagues from a planned interim analysis of the first 150/337 treatment naive patients randomised to either saquinavir/r (1000/100mg BID) of lopinavir/r (400/100mg BID) in a prospective open-label study.

All patients received tenofovir/FTC as background RTIs. The trials is being run in the USA, Canada, Puerto Rico, France and Thailand. The primary endpoint of the study is the percentage of patients with viral load <50 copies/mL at week 48.

The study enrolled 75% men and 25% women. Baseline characteristics were generally balanced between both arms and included mean CD4 count 114 cells/mm³ and viral load 5.1 log copies/mL, median age 36 years (range 20-63), 11% HCV coinfected. There is a slight trend in the lopinavir/r arm for patients to be more advanced compared to the saquinavir arm (40% vs 32% with CD4 counts < 50 cells/mm³; and 37% vs 28% with a prior AIDS defining event).

At week 24, there were 5 virologic failures in the saquinavir group (6.8%) versus 2 (2.6%) in the lopinavir group. 69% of saquinavir/r patients compared to 75% of lopinavir/r patients had achieved viral suppression < 50 copies/ml (p=0.43, NS between arms). Results were 74% vs 84% for ITT <400 copies/mL assay. Mean changes in CD4 and viral load were + 279 vs +294 cells/mm³ and -3.2 vs -3.5 logs copies/mL in the saquinavir/r vs lopinaivr/r arms respectively.

Fourteen patients discontinued saquinavir/r (3 due to side effects, 11 for non-safety reasons) vs 13 with lopinavir/r (4 side-effect s, 9 non-safety). There were no significant differences in Wk 24 efficacy measures.

Fasting lipid parameters were similar at baseline but changes by week 24 favoured the saquinavir arm. Total cholesterol increased above >/= 5.2 mmol/L (grade 1 or higher) in 7.9% patients on saquinavir vs 25% of patients on lopinavir arm (P<0.01); triglycerides increased to over 4.5 mmol/L (grade 2 or higher) in 1% vs 9% lopinavir/r patients (P<0.05).

Comment

Although this data is interesting, we need to wait for full 48-week analysis in order to see whether some of the small differences between the arms become more significant by the end of the study, and for a full comparison of the safety profile.

The question was also raised in a question after the presentation, about whether interim results should be presented.

As there is little recent data from randomised trials that compares saquinavir/r to other boosted PI-regimens, these results will be important. Results from the MaxCmin2 study, presented as a late breaker at the IAS conference in Paris in July 2003, had a similar design and showed results that benefited lopinavir/r. [2]

This study will show whether new formulations of both drugs have any impact on earlier results (Fortovase was used in the MaxCmin2 trial).