The strongest message from a two-day State of the Artconference on anti-retroviral therapy for adult HIV-infectedpatients was that when it comes to treating this dread disease,we're still in the Stone Age.
This presents a daunting challege to Kristine Gebbie, PresidentClinton's new AIDS policy coordinator, whose job it will be tofocus the government's response to the epidemic. As of the endof March, 289,000 Americans have been diagnosed with AIDS,and 182,275 have died from the disease since June 1, 1981,according to the Centers for Disease Control and Prevention.
The 18 leading researchers and 24 presenters and panelistsassembled by the National Institute of Allergy and InfectiousDiseases (NIAID) of the National Institutes of Health last weekwere charged with addressing questions of when nucleosidetherapy should be initiated; what is the best anti-retroviraltherapy for naive patients; whether, under variouscircumstances, one should switch drugs; and finally, what formof anti-retroviral therapy to use on patients who have failedtheir initial treatment.
The purpose was to provide physicians with new guidelines.
The panel combed through the relevant studies thoroughly,examining subsets of data from each and analyzing their ownanalysis.
Most of the studies presented over the two days of opensessions pointed in the same general directions. AZT isgenerally somewhat superior to the other nucleosides, andswitching therapies after eight weeks can improve efficacy. Theweakness of the drugs was evident from the fact that change inviral phenotype from non-syncytia to syncytia overwhelmedany effects from changes in treatment.
And the congruence of the studies seemed all the moreremarkable because the effects of manipulating the drugs wereso subtle -- a testament, if anything, to the quality of theresearch.
Nonetheless, scientists' ability to understand the naturalhistory of the virus has been stymied, Robert Coombs,professor in the departments of medicine and laboratorymedicine, University of Washington, Seattle, complained toBioWorld.
"All these drugs are being compared against nothing exceptanother drug" because the people with AIDS community'sinsistence upon treatment had deprived scientists of placebo-controlled studies, Coombs told BioWorld. "I think we areseeing the consequences of that right now. ... We don't knowhow much (benefit to patients) is coming from medicalmanagement versus the drug."
At the end of the open sessions, most of the researchersseemed to agree that the details of therapy should be left todoctor and patient. But "no one is saying throw your hands upand do nothing," Coombs insisted to BioWorld, "because there isa benefit that we are not currently able to assess."
Some researchers proposed addressing the ambiguitiesinherent in the data with a large, simple trial. But David Cooper,for one, disagreed. "Nucleosides are not the answer," theprofessor of immunology at the National Centre in HIVepidemiology and clinical research, the University of New SouthWales in Sydney, Australia, told BioWorld.
"They have limited duration of benefits," Cooper said. "All thestudies are reflecting that. Wait until there are better drugs, orcombinations of drugs, but don't put large resources into alarge, simple trial."
"We've been studying AZT versus the other two (ddI and ddC)or combinations of the other two for six years, and we arefinding they are still not very effective," Robert Darga, of theNational Association of People with AIDS (PWA) told BioWorld.
"There seems to be an unspoken assumption that initialtherapy will be non-therapy," he continued, "and I don't thinkthe discussion of combination therapy has done anything tochange that."
James Kahn's account of his advice to patients underscored howlittle support the science provides for clinical decision-making.The clinical professor in the department of medicine, AIDSdivision, at the University of California, San Francisco, said hetold patients there is an advantage to switching to ddI after 16weeks until studies showed that making the switch after eightweeks conferred an advantage.
"They come back to me eight or 16 weeks later and say, 'Nowwhat should I do?' And I switch to the old sawhorse, 'If it ain'tbroke, don't fix it.' "
-- David C. Holzman Washington Editor
(c) 1997 American Health Consultants. All rights reserved.