Saquinavir: Major Study Shows Survival Benefit in Treatment-Naive Patients

The largest trial ever conducted in AIDS, enrolling over 3400 volunteers with little or no prior HIV treatment, found that the three drug treatment saquinavir (Invirase(R)) plus AZT plus ddC reduced disease progression or death by 50%, compared to AZT plus ddC, a result which was highly statistically significant (p=0.0001). Deaths alone were reduced by about 42 percent, but due to the smaller number of deaths, this result was not quite statistically significant (p=0.067). The trial, NV 14604, was conducted outside the United States by Hoffmann-La Roche, and reported to the investigators in a two-page executive summary; a more complete report is being prepared for publication.

Among those entering the trial, the median CD4 count was about 200, and the median viral load was about 100,000. They either had no prior antiretroviral treatment, or no more than 16 weeks of AZT. The median time on study treatment was 14 months, and the median time of followup for clinical endpoints was 17 months. The saquinavir dose and formulation used was the same as that marketed until now in the U.S.

This is the only trial to prove clinical benefit from using a protease inhibitor in treatment-naive (or minimally treated) patients; the other clinical-endpoint trials were all in volunteers who had been more heavily treated with antiretrovirals. Combination treatment including a protease inhibitor is already well accepted in the U.S. for initial HIV therapy; therefore, these results may have little impact on the U.S. standard of care. But they could strengthen the case for making sure that all those who need the accepted treatments have access to them. And in Europe, where many patients still start treatment without a protease inhibitor, this trial may change the standard of care.