BARCELONA (July 10, 2002) – Clinical study results presented today indicate that HIV patients who switched their twice-daily protease inhibitor regimen of "boosted" saquinavir, by increasing the dose of saquinavir and minimizing the booster dose of ritonavir, were able to maintain viral suppression below 400 copies/mL with substantial reductions in triglycerides and cholesterol. These data were presented in an oral session at the XIV International AIDS Conference (IAC) in Barcelona, Spain, July 7-12, 2002.

"Results from the Switch Study demonstrate that patients can maintain viral suppression on a boosted saquinavir regimen without being exposed to the adverse events associated with higher doses of ritonavir," said Dr. William O’Brien, lead investigator in the Switch Study, and Professor of Infectious Diseases, University of Texas Medical Branch, Galveston, Texas. "In addition, by lowering levels of triglycerides, patients may be able to reduce their chance of developing cardiovascular events and lypodystrophy, growing concerns for HIV patients on long-term antiretroviral therapy."

Lipodystrophy is a disturbance of fat metabolism that manifests most commonly in HIV/AIDS patients as changes in body shape and composition. High levels of triglycerides observed in patients on an antiretroviral drug regimen including protease inhibitors have been associated with a higher severity of lypodystrophy [i]. Recent studies have concluded that increases in triglyceride levels could be considered a predictive marker of lypodystrophy in patients receiving antiretroviral therapy [ii]. High levels of cholesterol are associated with an increased risk of cardiovascular disease. Studies are ongoing to determine the link between protease inhibitors and cardiovascular disease.

Further data from the MaxCmin 1 trial showed that changes in lipids were significantly less in the saquinavir arm compared to the indinavir arm in weeks three and four.

In the Switch Study, 21 patients who had been receiving saquinavir/ritonavir dosed at 400 mg/400 mg BID for at least six months and who exhibited undetectable (less than 400 copies/mL) plasma HIV-RNA levels were randomized to continue on saquinavir/ritonavir 400/400 or to switch to saquinavir/ritonavir, dosed at 1000 mg/100 mg BID. After six months, in patients with dose modification (n=11), fasting serum triglyceride levels fell from 488 to 329 mg/dl, and cholesterol levels fell from 259 to 227 mg/dl. In the control group (n=10), fasting serum triglyceride levels were increased from 210 to 237 mg/dl, and cholesterol levels were increased from 206 to 231 mg/dl. None of the patients in the study who switched their dosing regimen to1000 mg/100 mg had increases in viral load above 400 copies/ml after 24 weeks, while four patients who remained on the 400 mg/400 mg dose had such increases.

Saquinavir is a member of the class of anti-HIV drugs known as protease inhibitors (PIs). PIs block a part of the HIV reproduction process involving the HIV protease, thus preventing the formation of new infectious HIV particles. Saquinavir is almost always used in combination with at least two other anti-HIV drugs and has been shown to significantly improve survival and reduce the occurrence of AIDS-defining events for people infected with HIV. Saquinavir is not a cure for HIV.

Boosting saquinavir with low doses of ritonavir allows more saquinavir to be absorbed into the blood and keeps saquinavir in the body for longer. The benefit for patients is that using this approach it is possible to reduce the dosing frequency together with the required number of capsules while still maintaining therapeutic drug levels.

In June of 2002 the Committee for Proprietary Medicinal Products (CPMP) granted a positive opinion for both INVIRASE™ (saquinavir hard gel capsules) and FORTOVASE™ (saquinavir soft gel capsules) to include co-administration with a low dose of ritonavir for the treatment of human HIV. The corresponding Commission Decision for the dosage schedule (1000mg saquinavir BID in combination with ritonavir 100mg BID) is expected by the end of August 2002.

The new schedule allows for the use of both saquinavir formulations, INVIRASE™ and FORTOVASE™. The new saquinavir/ritonavir schedule is also recommended in the new draft WHO guidelines, "Scaling up antiretroviral therapy in resource limited settings: Guidelines for a public health approach".

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