By Charles Craig

Researchers juggling drugs to find effective treatmentsfor AIDS presented more evidence Tuesday at a SanFrancisco conference that a combination of therapiesappears to offer the most effective method of fighting theinfectious disease.

In one National Institutes of Health (NIH) study, Merck& Co.'s protease inhibitor was tested in tandem withChiron Corp.'s Proleukin, or interleukin-2.

The study _ conducted by the NIH's National Instituteof Allergy and Infectious Diseases (NIAID) andsponsored by both Merck and Chiron _ is among thefirst trials to evaluate the combination of an antiviral drugand an immune system response therapy.

In another study, U.K.-based Glaxo Wellcome plc's testsof AZT with 3TC revealed data showing the combinationimproved quality of life for AIDS patients. Glaxolicensed 3TC, which like AZT is a nucleoside analog,from Biochem Pharma Inc., of Laval, Quebec. Thefindings apparently have added strength to datademonstrating that AZT and 3TC work better togetherthan AZT alone when examining the combination'seffectiveness against the standard surrogate markers usedto evaluate AIDS drugs.

Results of the Merck-Chiron and Glaxo-Biochem studieswere presented Tuesday at the 35th InterscienceConference on Antimicrobial Agents and Chemotherapy.

Ed Hurwitz, an analyst with Robertson, Stephens & San Francisco, said the various combination therapystudies presented at the conference clearly demonstratethat more than one antiviral drug will be used to fightHIV.

"The bottom line," Hurwitz suggested, is that the AIDSdrug market will involve "multiple players and multiplecombinations" of therapies with patients "switched fromone combination to another based on mutation patternsand susceptibility of the virus to the variouscombinations."

The NIAID trial involving Emeryville, Calif.-basedChiron's Proleukin and MK-639, the protease inhibitorunder development by Merck, of Whitehouse Station,N.J., tested IL-2's ability to boost production of immunesystem cells and the protease inhibitor's effectiveness inpreventing HIV replication.

Researchers said the two-drug combination was safe andwell tolerated in the Phase II trials. And in patients whodid not experience an increase in CD4 counts withProleukin alone, the addition of MK-639 boosted thenumber of those immune system cells. HIV levels insome patients also were lowered. CD4 counts and viralload are two standard surrogate markers used to judgeeffectiveness of AIDS drugs.

Chiron's spokeswoman, Kimberly Kraemer, said thePhase II studies are ongoing and NIAID is expanding thetrials. She also said Chiron is exploring potentialcollaborations for use of IL-2 with protease inhibitors asan AIDS therapy. The company currently has Proleukin inPhase II trials for AIDS. The drug already is on themarket in the U.S. as a treatment for kidney cancer.

No protease inhibitor has yet been approved by the FDAfor AIDS. Switzerland-based Roche Holdings Ltd. earlierthis month was the first to file a new drug application(NDA) for its protease inhibitor. Merck is expected tosubmit its NDA by early 1996. Abbott Laboratories, ofAbbott Park, Ill., also has a protease inhibitor in late-stageclinical trials.

Vertex Pharmaceuticals Inc., of Cambridge, Mass., andAgouron Pharmaceuticals Inc., of La Jolla, Calif., haveother versions of protease inhibitors in earlier stages ofdevelopment.

Protease inhibitors, which attack HIV at the end of itsreplication cycle in an attempt to stop its proliferation, areconsidered less toxic than nucleoside analogs, whichtarget the virus earlier in the cycle. Among the dualtherapies being tested are combinations of proteaseinhibitors and nucleoside analogs.

The Glaxo Wellcome quality of life studies involvedpatients enrolled in European and North American trialsof AZT and 3TC. Those studies showed that together thedrugs increased CD4 counts and lowered HIV levelsbetter than AZT alone. Based on achievement of thosesurrogate markers Glaxo has applied for approval of 3TCto use in combination with AZT in Europe, the U.S. andCanada.

In the data presented in San Francisco, 205 of the sickestpatients _ those with CD4 counts between 100 and 300_ were given a standard HIV health status questionnaireduring their treatments. The mean length of time coveredin the surveys was 36 weeks and the patients weredivided into three treatment groups. They received AZTin combination with one of two doses of 3TC or ddc,which is another nucleoside analog marketed by Roche.

The findings, according to Glaxo's researchers,demonstrated patients taking the lower dosage (150 mg)of 3TC with AZT achieved statistically significantimprovement in physical function, energy level andability to perform usual activities. n

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