One of the problems in HIV drug development is that companies most want to test their drugs on treatment-naive patients, where it is easy to show success--and least want to test with advanced patients who have already failed multiple antiretroviral regimens, where it is harder to market one- size-fits-all medicine.

Also, companies tend to avoid working together with competitors--a particular problem for patients who have become resistant to many drugs, and need at least two experimental treatments in order to put together a regimen likely to be effective enough to prevent more resistance development.

Heavily pre-treated patients are in many ways the most realistic test for a new drug, because any problems or deficiencies are likely to be found early, and drugs which work consistently in this population are likely to be outstanding for other patients as well. But companies typically think short term instead of years ahead.

The Coalition for Salvage Therapy came to together in 1998 to advocate for persons with advanced HIV infection and multiple treatment failures; it is seeking better research (especially research with multiple experimental drugs), and also the earliest possible access for patients who most urgently need new treatments. AIDS Treatment News interviewed activist Linda Grinberg of FAIR (Foundation for AIDS and Immune Research) about the CST's current activities, history, and future.

Linda Grinberg: Our initial focus was primarily directed at Abbott, simply because their new protease inhibitor, ABT-378, was the furthest along in development. After several contentious meetings and conference calls, through the CST's efforts, Abbott finally agreed to our proposal for a limited early access program in 1999, which is now underway. While access has received the most attention, the CST has also worked to convince Abbott and other pharmaceutical companies to do "true" salvage studies--to conduct clinical research in MDR (multi-drug resistant) patients. Almost three years ago, Abbott had stated that they were not interested in developing another "me too" protease inhibitor, yet they were reluctant to test their drug in MDR patients.

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We had repeatedly brought up this issue at various meetings over a two year period, and finally this March got the company to agree to do some very small, "proof of concept" trials, in collaboration with Gilead on PMPA and with Trimeris on T-20.

We had hoped these trials would begin earlier in order to have some preliminary data on combining these experimental agents, prior to the larger expanded access program, which will begin in January 2000.

Once Abbott agreed to the initial compassionate use program, we shifted our focus to Gilead's PMPA, and were able to secure a limited access program that essentially mirrors the Abbott one. It is also now enrolling. [For more information, see "Tenofovir (PMPA) Compassionate Access Study Opens," above.]

James: Who should be credited with leading this effort?

Grinberg: Spencer Cox of TAG (Treatment Action Group) started the ball rolling. He initially wrote a letter to Abbott in November of 1998. Abbott's response triggered Dave Gilden and I to convert Spencer's letter into a consensus statement, which we began circulating in November/December of '98, garnering wide endorsements, which ultimately gave birth to the Coalition for Salvage Therapy (CST).

Spencer passed the baton to Lynda Dee (of AIDS Action Baltimore) and she has been acting as our ad hoc leader or "point person". There are perhaps 30-40 active members of the CST, but much of the "hands-on" work has been done by Dee, Carlton Hogan, Martin Delaney, Ben Cheng, Jules Levin, Mark Milano and others. Everyone's support at meetings and on conference calls has greatly helped this effort.

James: What are the current issues in getting the trials we need?

Grinberg: In addition to working with Abbott, we've been meeting and dialoguing with Gilead, Trimeris, Pharmacia & Upjohn and others, encouraging them to work together to address the problem of the growing number of "treatment failures" in the U.S.

There are now several collaborative protocols on the drawing boards. Our ongoing work is to ensure that such studies start quickly, within the timelines promised, so that we have some real-world data before these drugs are launched in the marketplace.

Initially, there was tremendous resistance to early access and salvage studies requiring collaborations, as these companies had no intention of working together.

We've managed to push through some of these barriers and convinced several companies to agree to conduct small, "proof of concept" studies. Unfortunately, these studies will be very small, and we have not yet been able to get collaborations using three experimental, multi-class agents, which may offer a better chance at a durable response.

We hope to establish a new paradigm, one which will be an important and critical component of all future clinical development plans for all new agents.

James: What do you see for the future?

Grinberg: In the past, to obtain early expanded access for those in need, we had to start from the ground up and keep reinventing the wheel, forming new coalitions for each new drug--for example, protease inhibitors, 1592, Amprenavir.

With the CST, we have been able to bring together a diverse group of community people, who years ago could not agree on much of anything, to work on protocol designs and criteria for early access to several drugs simultaneously. We have sought consensus on many issues, learning to work together cooperatively to develop a cohesive coalition with a strategy for the future.

Most importantly, once a new agent has demonstrated some level of activity and safety, and the optimal dose has been identified, the CST wants the companies to expect, plan and be prepared (with enough drug supply) for early access programs for those unable to construct viable regimens without these new agents.

The CST has established a structure, not without some growing pains, but one which will hopefully be ongoing. It is building unity and trust among activists who were formerly at odds, and from my perspective, that's a major accomplishment.

James: How can others be involved?

Grinberg: The Coalition is open to anyone who wants to participate. There is no formal structure or funding; people volunteer, and help us as they can.

Note: If you are interested in participating, contact the Coalition for Salvage Therapy by email at: baltoaids@aol.com