VANCOUVER, B.C. _ The first combination of two proteaseinhibitors _ ritonavir and saquinavir _ reduced HIV RNA by 99percent at six weeks, and does not have overlapping resistancepatterns, according to early study results to be presented Thursday atthe XI International Conference On AIDS.

The combination of ritonavir (Norvir, manufactured by AbbottLaboratories, of Abbott Park, Ill.) and saquinavir (Invirase,manufactured by F. Hoffmann-La Roche AG, of Basel, Switzerland)appeared to work synergistically to decrease the level of HIV in theblood and increase CD4 counts, researchers said Wednesday. Bothdrugs taken alone have been shown to prolong survival and delaydisease progression.

"The data show a more potent anti-HIV effect than would be seenwith either drug alone," said William Cameron, associate professor ofmedicine at the University of Ottawa. "Considering that Invirase andNorvir are the only two protease inhibitors that have been shown toextend life and slow early disease, this early combination data isencouraging."

The two-drug combination has been pushed by AIDS activistsbecause of the unique interactions between saquinavir and ritonavir,resulting in high therapeutic blood concentrations of both drugswhen taken together.

"For the first time, we have data that support what we had predicted_ that certain protease inhibitors such as saquinavir and ritonavircan be used synergistically," said Martin Markowitz, staffinvestigator at the AIDS Laboratory of the Aaron Diamond Institute,in New York. "This combination will become an important elementof future HIV treatments."

The safety and efficacy study enrolled 120 patients with CD4 countsbetween 100 and 500. Patients were randomized to receive one offour regimens combining 800 mg to 1,200 mg daily of both ritonavirand saquinavir. The early results were based on the doses of 400 mgtwice daily of ritonavir and saquinavir in one group and 600 mg twicedaily of ritonavir and 400 mg twice daily of saquinavir in anothergroup.

The 43 patients who completed six weeks of therapy had a mediandecrease in HIV RNA of 99 percent or 2.4 logs and a medianincrease in CD4 cells of 98.

Cameron noted that the apparent lack of cross resistance between thetwo drugs suggests that the combination could provide long-termtherapeutic benefits. However, tolerance and safety of the doublecombination were not presented Wednesday.

Earlier in the conference, Cameron presented data on the proteaseinhibitor AG1343 (Viracept, manufactured by AgouronPharmaceuticals Inc., of La Jolla, Calif.), showing that resistancepatterns in the drug differed from those in other protease inhibitors.The unique resistance pattern of AG1343 means that the drug shouldnot have cross resistance to the three approved protease inhibitors.Genetic analysis of HIV isolates from five patients showed the virusresistant to AG1343 was susceptible to four other protease inhibitors.

Markowitz also reported the first results from a study of patientsreceiving 750 mg of AG1343 in combination with zidovudine (AZT)and 3TC (Epivir). In all 11 patients treated for four months theamount of HIV RNA in plasma dropped below detection. The meanincrease in CD4 counts was 95 cells.

More than 700 patients currently are enrolled in Phase II/III clinicaltrials of AG1343 in the U.S. The pharmaceutical division of JapanTobacco, Inc., of Tokyo, is collaborating with Agouron in developingthe drug.

AIDS Alert is published by American Health Consultants, publisherof BioWorld Today. n

-- Skip Connett AIDS Alert Editor

(c) 1997 American Health Consultants. All rights reserved.