HIV Inhibitor: Boosted Saquinavir Shows Significant Safety Benefit Over Boosted Crixivan

Recent study results show that boosted saquinavir (saquinavir 1,000 mg with ritonavir 100 mg) reduced HIV to undetectable levels in significantly more patients than boosted Crixivan (indinavir 800 mg with ritonavir 100 mg) at 48 weeks, as a result of a higher discontinuation rate in the indinavir arm of the study due to adverse events.

Boosted saquinavir also led to significantly lower increases in key lipid measures, including fasting total cholesterol, LDL cholesterol and triglyceride levels, than boosted indinavir at 48 weeks. The results come from the MaxCmin1 trial, the first large, randomized study to compare boosted HIV protease inhibitor regimens.

Co-administering saquinavir and ritonavir to increase levels of saquinavir in the blood is an approved European Union treatment strategy. A Supplemental New Drug Application (sNDA) for the investigational twice-daily saquinavir dosing regimen is under review by FDA. Roche is developing a 500 mg tablet formulation of saquinavir.

"The results of the MaxCmin1 study show significantly more patients taking boosted saquinavir remained virologically suppressed than those on boosted indinavir at 48 weeks, probably because of a better toxicity profile for boosted saquinavir," said Mike Youle of the Royal Free Hospital in London, a study co-author. "As safety becomes an ever more significant factor in choosing anti-HIV therapy, these results should help guide physicians when initiating patients on a protease inhibitor-based regimen."

Fifty-seven percent of patients who received at least one dose of the saquinavir therapy had undetectable HIV levels (less than 50 copies/mL) at 48 weeks, compared to 46 percent in the boosted indinavir arm of the study at 48 weeks. More patients withdrew from the study due to side effects of boosted indinavir (41 percent) than from boosted saquinavir (28 percent). Among patients who completed 48 weeks of therapy, HIV blood levels were suppressed to less than 50 copies/mL in 79 percent of patients on boosted saquinavir and in 77 percent of patients on boosted indinavir.

Boosted indinavir caused a higher risk of elevating blood levels of lipids than boosted saquinavir in fasting total cholesterol (17 percent vs. 8 percent), LDL cholesterol (18 percent vs. 3 percent) and triglyceride levels (22 percent vs. 9 percent), according to the study.

One hundred patients had at least one severe and/or life threatening adverse event: 65 (41 percent) in the boosted indinavir arm vs. 35 (24 percent) in the boosted saquinavir arm. There was a higher number of renal (13 vs. 1), dermatological (18 vs. 3) and gastrointestinal (19 vs. 17) adverse events in the boosted indinavir arm of the study vs. the boosted saquinavir arm, respectively.

MaxCmin1 was designed and coordinated by the Copenhagen HIV Investigator Program (CHIP). Three hundred seventeen patients from 14 countries in North and South America and Europe participated.

The study, "Randomized Trial to Evaluate Indinavir/Ritonavir versus Saquinavir/Ritonavir in Human Immunodeficiency Virus Type 1 Infected Patients: The MaxCmin1 Trial" appeared in the Journal of Infectious Diseases (2003;188:635-642).

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