Important note: Information in this article was accurate in 2001. The state of the art may have changed since the publication date.
PRNewswire - October 31, 2001
"Adherence to HIV therapy is one of the most important factors in maximizing the potential to achieve improved virologic and immunologic outcomes. In studying simplified treatment regimens, our goal is to improve patient adherence to therapy," said Jeffrey A. Lederman, M.D., infectious disease specialist at Soundshore Medical Center, New Rochelle, New York, and U.S. investigator in the MaxCmin1 trial. "If the 24-week results of the MaxCmin1 study, which look promising, are borne out in extended follow-up, twice-daily FORTOVASE in combination with mini-dose ritonavir could become a tool in helping physicians to design dosing schedules customized for individual patients' needs."
About MaxCmin1
MaxCmin1, the first randomized trial to compare twice-daily protease inhibitors with mini-dose ritonavir, is an ongoing study which was designed and is being coordinated by the Copenhagen HIV Investigator Program (CHIP). Patients at 23 research sites in the U.S., Europe and South America are participating in MaxCmin1 study. At entry, 317 protease inhibitor-naive and protease inhibitor-experienced patients received either 1000 mg FORTOVASE with 100 mg ritonavir twice daily (n=148) or 800 mg indinavir with 100 mg ritonavir twice daily (n=158), both in combination with other antiretroviral agents. (The remaining 11 patients who were randomized did not initiate protease inhibitor therapy.) The primary objective of the study is to evaluate differences in virological failure between the two treatment arms.
After 24 weeks of treatment, in the strict intent-to-treat (ITT), missing equals failure analysis, 75 percent of patients in the FORTOVASE arm achieved an HIV RNA viral load of less than 400 copies/mL, while 60 percent of patients in the indinavir arm achieved a viral load of less than 400 copies/mL. When only patients who received at least one dose are included in the analysis, 79 percent of patients in the FORTOVASE arm had an HIV RNA viral load of less than 400 copies/mL, while 72 percent of patients in the indinavir arm had an HIV RNA viral load of less than 400 copies/mL. Baseline characteristics of patients in the two arms were similar. At baseline, patients in both arms had a median HIV RNA viral load of 4.0 log(10); 63 percent and 58 percent of patients, respectively, in the FORTOVASE and indinavir arms had HIV RNA viral loads above 400 copies/mL. Patients in both arms had prior exposure to a median of one protease inhibitor and two nucleoside reverse transcriptase inhibitors (NRTIs).
The investigators also collected the number of adverse events experienced by patients in each arm. Patients in the FORTOVASE arm reported a total of 45 adverse events at grade 3 or 4, including 12 patients who withdrew due to non-fatal adverse events, while patients in the indinavir arm reported a total of 75 adverse events at grade 3 or 4, including 31 patients in the who withdrew due to non-fatal adverse events. Two patients in each arm discontinued due to virological failure. The number and type of adverse events experienced by patients in the FORTOVASE and indinavir arms, respectively, included: nervous system (3 and 6), pulmonary (1 and 4), cardiovascular (0 and 2), renal (0 and 10), gastrointestinal (14 and 18), skin and hair (6 and 10), fatigue and/or fever (3 and 3), laboratory (16 and 15), and other (2 and 7).
About FORTOGENE
The FORTOGENE study, conducted at 20 research sites by a team of investigators in Spain, was designed to assess the antiviral activity and tolerability of twice-daily FORTOVASE with mini-dose ritonavir in heavily pre-treated patients and to evaluate the value of genotypic testing and drug level measurement in predicting virologic response. A total of 144 patients experiencing virologic failure after receiving multiple PI-based regimens (none had been previously treated with saquinavir) began treatment with 1000 mg FORTOVASE and 100 mg ritonavir twice daily. The mean viral load at baseline was 100,047 copies/mL, and the mean CD(4) count was 367 cells/l microgram. All patients were tested genotypically for resistance mutations at baseline using the Applied Biosystems 3100 DNA automated sequence.
Data from 102 patients were examined. An HIV RNA viral load decline of greater than 1.0 log(10) occurred in 75 percent of these patients after six months on treatment. Furthermore, 60 percent of patients reached an HIV RNA viral load of less than 50 copies/mL at six months. The average CD(4) count increased by 97 cells/l microgram.
The investigators determined that both genotyping and drug levels were independent predictors of a virologic response to FORTOVASE with mini-dose ritonavir, concluding that these measures may be useful in predicting which heavily pre-treated patients may benefit from such a regimen. Eighty-nine percent of patients with less than four mutations responded to treatment (defined by an HIV viral load decline of greater than 1.0 log(10)), while 57 percent of patients with more than four mutations achieved a similar response. Mean plasma levels of FORTOVASE in virological responders versus non-responders were 1.45 micrograms/mL, and 1.30 micrograms/mL, respectively. Patients who experienced a virological response despite having more than four mutations showed high blood levels of FORTOVASE.
Five patients in the study withdrew as a result of gastrointestinal adverse events, two withdrew due to liver toxicity and five withdrew due to virologic failure.
More About FORTOVASE
The most frequently reported adverse events at least possibly related to treatment with FORTOVASE and of at least moderate intensity -- observed in previous preregistration trials evaluating a 1200 mg three-times-daily dosing regimen -- include nausea (17.8 percent), diarrhea (15.6 percent), abdominal discomfort (13.3 percent) and dyspepsia (8.9 percent). FORTOVASE should not be coadministered with astemizole, terfenadine, ergot derivatives, cisapride, midazolam or triazolam, due to the potential for serious and/or life-threatening events. Concomitant use with lovastatin or simvastatin is also not recommended; caution should be exercised with other HMG-CoA reductase inhibitors metabolized by the CYP 3A4 pathway. Exacerbation of chronic liver dysfunction has been reported in patients treated with FORTOVASE. Patients should be informed that redistribution or accumulation of body fat may occur in patients receiving protease inhibitors and that the cause and long-term health effects of these conditions are not known at this time. There have also been reports of hyperglycemia, new onset or exacerbation of diabetes and of spontaneous bleeding in patients with hemophilia. Please refer to the complete product information for detailed safety information for FORTOVASE.
About Roche
Hoffmann-La Roche Inc. (Roche), based in Nutley, N.J., is the U.S. prescription drug unit of the Roche Group, a leading research-based health care enterprise that ranks among the world' s leaders in pharmaceuticals, diagnostics and vitamins. Roche discovers, develops, manufactures and markets numerous important prescription drugs that enhance people's health, well-being and quality of life. Among the company' s areas of therapeutic interest are: dermatology; genitourinary disease; infectious diseases, including influenza; inflammation, including arthritis and osteoporosis; metabolic diseases, including obesity and diabetes; neurology; oncology; transplantation; vascular diseases; and virology, including HIV/AIDS and hepatitis C.
For more information on the Roche pharmaceuticals business in the United States, visit the company's website at: http://www.rocheusa.com.
Crixivan(R) is a registered trademark of Merck & Co., Inc.
For further information about FORTOVASE(R) Patients can call: (800) 910-4687 Healthcare Professionals: (800) 526-6367 Roche HIV Therapy Assistance Program: (800) 282-7780 FORTOVASE Web site: http://www.Fortovase.com
For a copy of the FORTOVASE product package insert with complete prescribing information please call: Shelley Rosenstock at (973) 562-2373.
FORTOVASE(R) (saquinavir) is a registered trademark of HLR Technology Corporation, an affiliated company of Hoffmann-La Roche Inc.
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