Treatment-naive HIV patients treated with the protease inhibitor (PI) saquinavir (Invirase) boosted with ritonavir (Norvir) achieved similar viral suppression and increases in CD4 cells as those treated with the PI lopinavir/ritonavir (Kaletra), according to final, 48-week results of an international head-to-head trial supported by Roche Laboratories. In addition, fewer patients treated with Invirase developed elevated triglyceride levels compared with those receiving lopinavir/ritonavir.

The data from Roche's "Gemini" study were presented at the 11th European AIDS Conference in Madrid (October 24-27, 2007). Following are edited excerpts from a Roche press announcement of the study results:

"We urgently need HIV treatment options with more favorable lipid profiles, and this is why I welcome the results from the Gemini study," said Professor Sharon Walmsley, Associate Professor of Medicine in the Division of Infectious Diseases, University of Toronto, Canada, and lead investigator on the Gemini study. "These data are of considerable importance because they confirm that Invirase [in combination with low-dose ritonavir] offers treatment-naive patients an effective treatment to control the virus with significantly smaller increases in triglyceride levels than lopinavir/ritonavir, the most commonly prescribed PI."

Current treatment guidelines for highly active antiretroviral therapy (HAART) include a [ritonavir]-boosted protease inhibitor (PI/r) as an option for first-line treatment of HIV-infected patients. However, all PI-based regimens can be associated with varying degrees of lipid abnormalities, potentially increasing the risk of developing metabolic syndrome and long-term risk of cerebrovascular and cardiovascular disease. As people with HIV are living for longer due to advances in treatment, it is especially important for trials to explore, and for physicians to consider, the lipid profiles of the various treatment options.

The Gemini Study: Summary of 48-Week Results

These findings are from the final, 48-week analysis of all 337 patients in the Gemini study.

The data show that boosted Invirase 500 mg was not inferior to lopinavir/ritonavir, with 64.7% and 63.5% of patients treated with Invirase/ritonavir and lopinavir/ritonavir, respectively, achieving undetectable HIV (less than 50 copies/mL of blood). A similar number of patients in both groups (approximately 73%) achieved undetectable HIV of less than 400 copies/mL.

Furthermore, the rate and extent of increases in CD4 counts were comparable in both groups, with a median increase from baseline of 178 cells/mm3 for the Invirase/ritonavir-treated patients and 204 cells/mm3 for lopinavir/r patients.

Finally, the results demonstrate that there was no statistically significant difference in the number of virological failures between the 2 treatment groups. Adverse events were reported with similar frequency in both study arms.

At 48 weeks, patients treated with Invirase/ritonavir showed a lower median increase in their total triglycerides (TG) than patients treated with lopinavir/ritonavir (increase of 14 versus 55 mg/dL).

In addition, the number of Invirase/ritonavir-treated patients who experienced an increase in their lipid levels above those recommended by National Cholesterol Education Program (NCEP) guidelines, as measured by total cholesterol and triglyceride levels, was numerically lower than those treated with lopinavir/ritonavir.

In the Invirase/ritonavir group, the proportion of patients with total cholesterol levels above those recommended in guidelines at week 48 was 31% vs. 39% for the lopinavir/ritoavir group; in TG levels, 1% vs. 9%; and for LDL levels, 34% vs. 24%.

[Editor's Note: The differences between the 2 drugs were not statistically significant].

About the Gemini Study

The Gemini study was a Phase IIIb multi-center, randomized open-label, 48-week study, designed to evaluate the efficacy and safety of Invirase 500 mg plus ritonavir versus lopinavir/ritonavir. These treatments are given at their approved twice-daily dosages in combination with 2 nucleoside reverse transcriptase inhibitors (NRTIs; emtricitabine/tenofovir (Truvada), once daily) in treatment-naive adults.

Gemini enrolled 337 patients from Canada, France, Puerto Rico, Thailand, and the USA. Of note, the baseline characteristics of patients enrolled in the Gemini study indicated they had more advanced disease compared with patients in several recently published trials, such as KLEAN and ARTEMIS.

The primary endpoint of the trial was the number of patients with an HIV-1 RNA viral load of less than 50 copies/mL at week 48. Secondary endpoints were time course of virological suppression, time course of CD4 cell increase, and safety as assessed by clinical and laboratory adverse events, serious adverse events, and deaths.

About Invirase

Invirase, originally approved by the US Food and Drug Administration (FDA) in 1995, was the first protease inhibitor on the market. In December 2003, the FDA approved Invirase for use in boosted dosing regimens with ritonavir (1000 mg Invirase/100 mg ritonavir twice daily). Co-administering Invirase with ritonavir enhances therapeutic blood levels of the drug ("boosting") and enables simplified dosing.

The Invirase 500 mg formulation received approval from the FDA in December 2004 and from the European Commission in May 2005.

The new formulation significantly simplifies the Invirase dosing regimen by reducing the daily tablet count by more than half, from 5 tablets twice-daily to 2 tablets twice-daily.

10/30/07

Reference

S Walmsley, K Ruxrungtham, J Slim, and others. Saquinavir/r (SQV/r) BID versus lopinavir/r (LPV/r) BID, plus emtricitabine/tenofovir (FTC/TDF) QD as initial therapy in HIV-1 infected patients: the GEMINI Study. 11th European AIDS Conference. Madrid, Spain. October 24-27-002007. Abstract PS1/4.