VANCOUVER, B.C. _ Armed with new data showing that proteaseinhibitors can maintain HIV RNA suppression beyond 24 weeks,researchers set the stage Sunday for an upbeat, week-long AIDSconference that promises to solidify the foundation of a fast-growingparadigm shift in HIV treatment.
Researchers at Merck & Co., of Whitehouse Station, N.J., willpresent the new data on the company's protease inhibitor, indinavir(Crixivan), Thursday at the XI International Conference On AIDS,which began on Sunday and will run through Thursday.
In a satellite symposium Sunday, however, Jeffrey Chodakewitz,senior director of clinical research for infectious diseases at Merck,said preliminary data suggests the same antiviral activity seen inpatients on indinavir monotherapy after 24 weeks treatment generallyis maintained through 48 weeks of therapy.
In March, he told an FDA advisory committee that viral activitydeclined for more than 48 weeks in patients taking indinavir incombination with other drugs. Apparently the latest data are centeredon monotherapy.
Merck received marketing clearance for indinavir in March after arecord-setting 42-day FDA review. (See BioWorld Today, March 15,1996, p. 1.)
"If you look at these patients, the proportion who have RNA levelsbelow assay detection by 24 weeks, 30 percent to 40 percent ofpatients have achieved that response," he said. "And indeed, thosesame patients have continued out to 48 weeks, which really reinforcesthe goals we have outlined."
In Phase III studies combining indinavir with one or more nucleosideanalogues (AZT and/or 3TC), up to 90 percent of patients haveachieved and maintained suppression of viral RNA levels similar tothat seen in patients after 24 weeks, he added. The actual significancein suppressing the virus below detectable levels will remaintheoretical until long-term studies are completed.
The excitement that pervaded the opening of the conference Sundaywas constrained by concerns that reducing virus to undetectablelevels in the blood still does not eradicate HIV from the body. Thelingering "embers" of the viral fire could eventually heat up andcause progression of disease. Scientific grasp of HIV pathogenesisweakens considerably after the first or acute phase of infection inwhich as many as 10 billion viral particles are produced anddestroyed each day.
David Ho, director of the Aaron Diamond Research Center, in NewYork, discussed two caveats that temper enthusiasm about viralsuppression.
First, while the half-life of the virus in the first phase of infection isvery short _ half the virus clears in the blood in about six hours _the rate of viral decay may be slower in the second phase of infectionduring which latently infected cells become activated.
"All of us have noticed that after weeks of treatment the viral decayevents take on a different slope," he said. "There seems to be a half-life in the order of several weeks. Those are for the compartments weknow about. If there are additional compartments that are small andwould decay slower, that would affect the ultimate answer."
Second, there is the issue of "sanctuary" _ the new buzz worddescribing the likelihood that undetectable pools of virus are hidingout in other parts of the body, such as the lymph nodes, the brain, andthe genital tract. While these pools may not cause the kind ofphysical damage that the virus wreaks on the immune system, theycould remain untouched by treatment and produce virus capable ofinfecting CD4 cells, thus leading to disease progression, Ho said.
One of several planned trials for indinavir will measure viral loadchanges in lymphatic tissue, said Chodakewitz. Trials also are beingset up to combine indinavir with the non-nucleoside reversetranscriptase analogues.
New Groups Call For Vaccine Development
Citing the high cost of combination antiretroviral therapy, a newlyformed group of scientists and health care policy makers have issuedan "urgent global call" for resources to develop an AIDS vaccine.
With the cost of treating a patient with combination antiretroviraltherapy drugs exceeding $15,000 a year, the benefits of new drugresearch are beyond the grasp of the majority of the HIV-infectedpopulation, warned members of the International AIDS VaccineInitiative (IAVI), an independent, non-profit organization formedwith the help of the Rockefeller Foundation in New York.
The formation of IAVI was announced Sunday at the conferencehere. Supported by the World Bank and the Merieux Foundation, theglobal organization has the single purpose of accelerating vaccinedevelopment for developing countries, where nearly 90 percent ofnewly developing HIV infections are occurring.
While vaccine development hit a major snag last year in the U.S., "avaccine is possible and it is essential," said Seth Berkley, chairman ofthe initiative's board of directors. "The current vaccine developmenteffort is inadequate."
Berkley noted that biotechnology and pharmaceutical companieshave reduced sharply their commitment to vaccines; only threecompanies have advanced their products beyond Phase I clinicaltrials.
The initiative, temporarily based in New York, will work with anadvisory committee of scientists from nine countries to develop ascientific agenda and find new sources of funds for vaccinedevelopment.
"Vaccines have eliminated smallpox and halted polio and measles inmany parts of the world," said Margaret Johnston, IAVI's scientificdirector. "With the proper vision, scientific agenda, and globalcoordination, we can focus some of the best minds in the world ondeveloping a vaccine for AIDS _ something that I believe we canachieve in my lifetime."
Recent discoveries about HIV in humans, such as the fact that somebabies born to HIV-infected mothers are able to clear the infection,have provided encouragement that a vaccine can be developed, sheadded.
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.