Current treatment guidelines for highly active antiretroviral therapy (HAART) include a boosted protease inhibitor (PI) as an option for first-line treatment of HIV-infected patients. However, PI-based regimens can be associated with varying degrees of lipid abnormalities, potentially increasing the long-term risk of cerebrovascular and cardiovascular disease. As people with HIV are living longer due to advances in treatment, it is especially important to establish regimens that minimize the adverse effects on lipids to potentially reduce the risk of cardiovascular disease.

“The full interim results from the Gemini study further suggest that boosted Invirase may be a good choice for many patients, particularly those with increased cardiovascular risk,” said Dr. Jihad Slim, Infectious Disease Specialist, St. Michael’s Medical Centre and an investigator in the Gemini study. “We need to be able to offer safer options for patients on combination HIV therapy – and establishing a PI-based regimen that is associated with fewer lipid abnormalities could have a real impact on HIV management.”

Gemini: Summary of Full 24-Week Results
Efficacy results showed that 69.9 percent and 69 percent of patients, respectively, treated with Invirase/ritonavir (r) (n=166) and lopinavir/r (n=171) achieved undetectable HIV levels (less than 50 copies per mL of blood; ITT analysis). The same proportion of patients (81.3 percent) in both groups achieved undetectable of less 400 copies per mL of blood. Furthermore, the rate and extent of increases in CD4 counts were comparable in both groups, with a median increase from baseline of 127 cells per cubic mL of blood for patients in the Invirase/r group, and 134 cells for patients in the lopinavir/r group.

A total of 163 patients in the Invirase/r group and 168 patients in the lopinavir/r group were included in the safety analysis. At 24 weeks, patients treated with Invirase/r showed a lower median increase in their total cholesterol (TC) and total triglycerides (TG) than patients treated with lopinavir/r (increase of 17 versus 26 mg/dL for TC, and an increase of 14 versus 43 mg/dL for TG). In addition, there was a trend toward fewer Invirase/r-treated patients experienced an increase in their lipid profiles, above those recommended by the National Cholesterol Education Program and ACTG guidelines, than those treated with lopinavir/r. In the Invirase/r group, the proportion of patients with TC levels above those recommended in guidelines was 21.5 vs. 26.8 percent for the lopinavir/r group; for LDL levels, 49.7 vs. 40.5 percent; and in TG levels, 1.2 vs. 8.9 percent. In the Invirase/r group, five patients withdrew due to adverse events, and in the lopinavir/r group, 11 patients withdrew due to adverse events.

About the Gemini Study
The Gemini study is a Phase IIIb, multi-center, randomized, open-label, 48-week study, designed to evaluate the efficacy and safety of Invirase/r versus lopinavir/r. These treatments are given at their approved twice-daily dosages in combination with two nucleoside reverse transcriptase inhibitors (NRTIs; emtricitabine/tenofovir [Truvada], once daily) in treatment-naïve adults. Gemini enrolled 337 patients from Canada, France, Thailand and the U.S., including Puerto Rico. The primary endpoint of the trial is the number of patients with an HIV-1 RNA viral load of less than 50 copies per mL of blood at week 48. Measurement of lipid safety parameters was a secondary endpoint of the study. The results announced today are the second of two planned interim analyses.

More About Invirase
INVIRASE in combination with ritonavir and other antiretroviral agents is indicated for the treatment of HIV infection. The twice-daily administration of INVIRASE in combination with ritonavir is supported by safety data from the MaxCMin1 study and pharmacokinetic data. The efficacy of INVIRASE with ritonavir has not been compared against the efficacy of antiretroviral regimens currently considered standard of care.

INVIRASE is contraindicated in patients with clinically significant hypersensitivity to saquinavir or to any of the components contained in the capsule. INVIRASE/ritonavir should not be administered concurrently with terfenadine, cisapride, astemizole, pimozide, triazolam, midazolam or ergot derivatives. Inhibition of CYP3A4 by saquinavir could result in elevated plasma concentrations of these drugs, potentially causing serious or life-threatening reactions, such as cardiac arrhythmias or prolonged sedation.

INVIRASE when administered with ritonavir is contraindicated in patients with severe hepatic impairment. Patients with hepatic impairment have not been studied and caution should be exercised when prescribing saquinavir in this population. Concomitant use of INVIRASE with lovastatin or simvastatin is not recommended. Caution should be exercised if HIV protease inhibitors, including INVIRASE, are used concurrently with other HMG-CoA reductase inhibitors that are also metabolized by the CYP3A4 pathway (eg, atorvastatin).

Concomitant use of INVIRASE and St. John’s wort (hypericum perforatum) or products containing St. John’s wort is not recommended. Garlic capsules should not be used while taking saquinavir as the sole protease inhibitor, due to the risk of decreased saquinavir plasma concentrations. For a complete list of drugs that should not be taken with saquinavir, please see TABLE 5 in the summary of complete product information.

New-onset diabetes mellitus, exacerbation of preexisting diabetes mellitus and hyperglycemia have been reported during postmarketing surveillance in HIV-infected patients receiving protease-inhibitor therapy. No initial dose adjustment is necessary for patients with renal impairment. However, patients with severe renal impairment have not been studied, and caution should be exercised when prescribing saquinavir in this population. There have been reports of spontaneous bleeding in patients with hemophilia A and B treated with protease inhibitors.

Elevated cholesterol and/or triglyceride levels have been observed in some patients taking saquinavir in combination with ritonavir. Redistribution/accumulation of body fat has been observed in patients receiving antiretroviral therapy. A causal relationship between protease-inhibitor therapy and these events has not been established, and the long-term consequences are currently unknown.

Varying degrees of cross-resistance among protease inhibitors have been observed. In clinical trials with saquinavir (1000 mg) in combination with ritonavir (100 mg) and other antiretrovirals, the grade 2, 3 and 4 adverse events occurring in ≥ 2% of 148 patients (considered at least possibly related to study drug or of unknown relationship): abdominal pain (6.1%), back pain (2%), bronchitis (2.7%), constipation (2%), diarrhea (8.1%), diabetes mellitus/hyperglycemia (2.7%), dry lips/skin (2%), eczema (2%), fatigue (6.1%), fever (3.4%), influenza (2.7%), lipodystrophy (5.4%), nausea (10.8%), pneumonia (5.4%), pruritus (3.4%), rash (3.4%), sinusitis (2.7%) and vomiting (7.4%).

INVIRASE is not a cure for HIV infection or AIDS. INVIRASE does not prevent the transmission of HIV.

About Roche
Hoffmann-La Roche Inc. (Roche), based in Nutley, N.J., is the U.S. pharmaceuticals headquarters of the Roche Group, one of the world’s leading research-oriented healthcare groups with core businesses in pharmaceuticals and diagnostics. For more than 100 years, the Roche Group has been committed to developing innovative products and services that address prevention, diagnosis and treatment of diseases, thus enhancing people's health and quality of life. An employer of choice, in 2006, Roche was named one of the Top 20 Employers (Science magazine), ranked the No. 1 Company to Sell For (Selling Power), and one of AARP’s Top Companies for Older Workers, and in 2005, Roche was named one of Fortune magazine’s Best Companies to Work For in America. For additional information about the U.S. pharmaceuticals business, visit our websites: http://www.rocheusa.com or www.roche.us.

###