Preliminary findings from a Phase III trial of HIV-infected patients shows that AZT may no longer be thefirst-line therapy for many patients.

A clinical trial sponsored by the National Institutes ofHealth has demonstrated that combination therapy ofanti-retrovirals in individuals with intermediate-stageHIV disease sometimes is superior compared to AZTmonotherapy to stave off the onslaught of AIDS andreduce the risk of death.

The study of 2,500 volunteers enrolled in the AIDSClinical Trials Group 175 (ACTG 175) showed that inpatients with initial CD4 T cells counts between 200 and500/mm2, ddi (didanosine), the combination of ddi pluszidovudine (AZT) and the combination of zalcitabine(ddC) plus AZT were each superior to AZT alone. Theeffectiveness of the treatments were evaluated accordingto declining CD4 T cell counts, onset of an AIDS-relatedinfection or death.

Specifically, investigators found that ddi alone or ddi incombination therapy with AZT was more effective inslowing the progression of the disease or ensuringsurvival.

Glaxo Wellcome plc manufactures AZT, Bristol-MyersSquibb makes ddi and Roche, ddC.

"ddi is looking quite good in comparison with AZT," saidIsadore Pike, Squibb's vice president for oncology andimmunology. ddi already is approved by the FDA as asecond-line therapy for AIDS treatment. "We'll be goingto the FDA soon to add a second indication for first-linetherapy," said Squibb spokeswoman Tracy Furey. Squibbis located in Princeton, N.J.

Using the clinical end points of an increase in CD4 T cellcounts, progression to AIDS or death, ddi or AZT incombination with either ddi or ddC "were all superior toAZT alone," said Pike. However, Pike stressed thefindings that ddi reduced the onset of death by 50 percent."This is the most significant clinical finding," he toldBioWorld Today in an interview. "A drug thatsignificantly reduces the risk of death in that patientpopulation is striking news."

However, Pike said he does not believe that AZT hasbeen supplanted as the first-line therapy for many AIDSand HIV-positive individuals. "Practitioners need to makea decision about which therapy to pick based on a numberof considerations, including the patient's experience witha particular drug, patient preference about a single agentor combination therapy, and the cost and convenience."

"Cost may be a determining factor for some patients," hesaid. "While the average wholesale price of a year'ssupply of AZT is $3,200, ddi is considerably cheaper at$2,100. Combined AZT and ddi therapy would cost$5,300 while AZT and ddC costs $5,500."

"The future certainly lies with combination therapy," saidJames Rooney, associate director of antiviral clinicalresearch for Glaxo Wellcome, of Research Triangle Park,N.C. Glaxo expects to obtain FDA approval before theend of the year for 3TC, another anti-retroviral thatRooney said is "10 to 100 times more potent than AZTand is well tolerated by patients."

The ACTG 175 appears to have been spared many of themitigating factors that have muddied AIDS trials in thepast, including high drop out rate and drug swappingamong patients in different treatment arms. Pike said thatinvestigators monitored the size of red blood cells usingmean corpuscular volume to determine if the participantsalso used AZT which increases the size of red blood cells."Those tests provided real good evidence that the patientswere clear of AZT," said Pike.

Patients were allowed to switch from one treatment armto another after the first clinical end point was reached,said Mickolos Salgo, director of Roche's virologydepartment. Roche is located in Nutley, N.J.

"Few patients switched until the first clinical end pointhad been reached," he said.

Limited information is available on the drugs' side effectsand impact on quality of life. That information will beunveiled this week at the 35th Interscience Conference onAntimicrobial Agents and Chemotherapy. n

-- Michele L. Robinson Washington Editor

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

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