The Bay Area Reporter - August 19, 1996
Bill Snow, ACT UP/Golden Gate Writers Pool

The pathogenesis debate

On Thursday David Ho, director of the influential and always-in-the-news Aaron Diamond Research Center, and Giuseppe Pantaleo, a senior researcher in Tony Fauci's intramural NIH lab, debated whether viral factors (Ho) or factors in the infected person's immune system known as host factors (Pantaleo) are the primary determinants of HIV pathology.

Ho made a very compelling argument, as he has done in many places, that "it's the virus, stupid," by emphasizing the importance of virus load, amount of virus transmitted (in monkeys), and the type of virus transmitted on disease course: "bad virus, bad outcome," he says. Pantaleo, whose work is on the immune system and how it responds to HIV, emphasized how host factors influence resistance and outcome to many infections. He summarized important new findings about the effect of genetics, an individual's immune type, and immune response chemistry on how the disease takes hold and progresses.

From the start, and in the end, both conceded that "it takes two to tango, the virus and the host." The difference is in emphasis and approach for research. And guess what? Virologists favor (and study) the virus, the immunologists the immune system. The research establishment is equipped and continues to support both lines of research, though we've certainly seen more progress in drug development against the virus than in immune therapies so far.

The vaccine debate

Tuesday's debate topic was, "Resolved that more fundamental research in vaccine development is required prior to the implementation of Phase III trials of HIV vaccines." Speaking in favor of fundamental research was John Moore, again from the Aaron Diamond Center (a fundamental researcher), vs. Edward Mbidde, of the Uganda Cancer Institute and chair of the research subcommittee of the Uganda National AIDS Committee. This debate was eagerly anticipated by some and dreaded by others given that this issue has been debated almost constantly in vaccine development circles since before the U.S. government decision in 1994 not to go ahead with gp120 vaccine efficacy trials in the U.S. A fair amount of heat (and hot air) had already been exchanged.

It would be easy, and true, to say that this is another issue where it also takes two to tango; fundamental research and clinical trials will both be needed to develop an effective vaccine. But here big resources, $25-40 million, would be needed to run an efficacy trial of a single vaccine, with thousands of volunteers and at least two years until an outcome, so the decision to go ahead cannot be made lightly or without consequences for other research funding. Unfortunately, a decision not to go ahead when appropriate could also have the grave consequence of allowing the epidemic to continue and never getting a definitive answer about a particular product or approach.

This debate was somewhat disappointing. Moore has been an outspoken adversary of Don Francis of Genentech/Genenvax, who insists that we have to test the gp120 vaccines now. Both Genentech and Moore's lab at Aaron Diamond have analyzed the same small number of infections from Phase II trials and have come up with diametrically opposed theories for them: Genentech that their vaccine may protect some, Moore's lab that that's nonsense.

Dr. Mbidde, on the other hand, represents his country, Uganda, which is in the epicenter of the epidemic without any significant healthcare resources for treatment or prevention. The Ugandan government has decided, more that any other country except perhaps Thailand, to pin its hopes on a vaccine and is cooperating fully with plans to test vaccines in their country. So, in a sense the two debaters were arguing to cross purposes: Mbidde that there is a desperate need for a vaccine (no argument there) and that developing countries are willing to cooperate in testing potential vaccine candidates, while Moore, when he wasn't beating the never-say-die gp120 horse, was arguing that we need to develop better candidates first.

In fact, the real issue now is that a second generation approach, with ALVAC canarypox vaccine and gp120 boosters, is the hands-down favorite for moving ahead into field testing, perhaps as soon as 1998. Moore skirted the issue of whether this product should move to efficacy trials because it's really too soon to make that decision. He did express concern that it may be moved ahead just to be testing something.

So, with no real damage done to either side, we can expect to hear a lot more about this decision as the canarypox approach moves into and out of Phase I testing in Uganda and Phase II testing in the U.S. next year. Legitimate and compelling arguments can be made for moving as rapidly as possible into efficacy trials to answer scientific questions necessary for further vaccine development and to move aggressively with anything that may provide even partial protection. Unfortunately, those arguments weren't made very well in this debate, nor are they often made without being bogged down in promoting a specific product. On a national scale, the real debate is just beginning.

Bill Paul speaks

In a related matter, Dr. Bill Paul, whose current prestigious and influential assignment is head of the NIH Office of AIDS Research, gave a very sobering lecture in the Distinguished Lecturer Series on Monday, devoted almost completely to untapped opportunities in vaccine development. Before taking on the many-headed beast of OAR, Dr. Paul has been a distinguished immunologist, so he knows whereof he speaks. In fact, his talk was much more based on his immunologist role than the political role of OAR Director.

In effect what he said was that "vaccine research for HIV has been notable for its sophisticated use of modern molecular engineering techniques," but that "we are using immunization techniques that might have been employed 50 years ago." He then showed how recent advances in understanding immune regulation could be, and have not yet been used to maximize the effectiveness of vaccines. It was a striking and bold statement from the head of all NIH AIDS research to focus on vaccines as essential to control the epidemic, and to propose a personal and revolutionary set of priorities for a new vaccine development research agenda.

There were several other sessions on various aspects of vaccine development with very little new science, but the importance of vaccines got more attention at this conference than any other, largely because of access and price problems with the new drugs. In addition, the International AIDS Vaccine Initiative, a new global program designed to accelerate development of an HIV vaccine for use throughout the world, was formally launched. It will be described in another article.
960819
BR960803

Always watch for outdated information. This article first appeared in 1996. This material is designed to support, not replace, the relationship that exists between you and your doctor.

AEGiS presents published material, reprinted with permission and neither endorses nor opposes any material. All information contained on this website, including information relating to health conditions, products, and treatments, is for informational purposes only. It is often presented in summary or aggregate form. It is not meant to be a substitute for the advice provided by your own physician or other medical professionals. Always discuss treatment options with a doctor who specializes in treating HIV.

Copyright ©1980, 1996. AEGiS. All materials appearing on AEGiS are protected by copyright as a collective work or compilation under U.S. copyright and other laws and are the property of AEGiS, or the party credited as the provider of the content. .