The Bay Area Reporter - January 19, 1998
Matthew Sharp, ACT UP/Golden Gate Writers Pool

Several ACT UP Writers Pool articles have focused on ill-designed AIDS clinical trials today. Poor design is resulting in declining enrollment. Research institutions are struggling to get people with HIV into trials at a time when most drugs that have proven effective are available at the pharmacy or through various assistance programs. One of the biggest incentives for entering a study, drug access, is no longer the driving factor it once was, when people with AIDS were more desperate. Also, opportunistic infection studies have become difficult to enroll because fewer people are experiencing clinical manifestations of AIDS. Other design issues such as strict entry criteria, which restrict people who have been on previous therapy, have placed a stranglehold on AIDS research. Therefore, trials enroll too slowly, and by the time studies are completed, the information gained is often outdated and not useful.

Researchers and people with AIDS are urging a new system of studying HIV in this era of potent combination therapies, viral resistance, and overwhelming confusion about how to best use the drugs. More answers need to be found in people who have used all of their treatment options. One effective strategy would be to employ longterm follow-up studies, which can answer questions about toxicities and effectiveness in a more real-world scenario.

Advantages

Activists have been demanding longterm studies for years. Trials now look at a snapshot of a patient's treatment history. They involve defined subgroups comparing one drug against another in a fixed duration or short term. This has been a requirement of the FDA in order to approve the drug for marketing. But in the real world, head-to-head, fixed duration studies do not accurately portray the way people with AIDS should be treated.

The AIDS Clinical Trials Group is one research group devising a new system of following people over the long term. Funded through the National Institutes of Health, the ACTG is the largest of the federal institutions performing AIDS clinical research. Not always known for its aggressive, cutting edge research, the ACTG is now leading the field with a "matrix" system for studying people with AIDS. The new system, ACTG Longitudinal Linked Randomized Trials (ALLRT), will attempt to address some of the fundamental problems experienced in AIDS research. The group intends to follow a large number of patients and roll them into subsequent studies with the goal of achieving longterm suppression, immunologic reconstitution, and prevention of disease progression and opportunistic complications.

ALLRT is the brainchild of the Scientific Agenda Steering Committee of the Adult AIDS Clinical Trials Group (AACTG). Mark Jacobson, an AIDS researcher at San Francisco General Hospital, is a principal investigator and newly named chair of the AACTG Complications Research Agenda Committee, which sets priorities for research in AIDS complications. When asked why ALLRT would be important in today's research picture, Jacobson replied, "Everyone with HIV disease will be better served by trials that answer the most important questions related to the impact of the new antiretroviral treatments on the longterm health of people with this disease."

He added, "Monitoring a very large group of patients over many years, this type of longterm follow-up of patients who have been enrolled in randomized trials is not done in industry-sponsored trials."

With longterm follow-up through ALLRT, patients will be randomized to two or more treatment arms and followed until their virus breaks through or becomes detectable. Then they will move on to another trial, based on what treatment they need and what is available at that point. If no trials fit their criteria, they will continue to be monitored until the right study comes along. Other patients will enter during the course of ALLRT in other trials, depending on their resistance status, prior drug history, and viral load, and the matrix will grow, build, and interconnect.

One big complaint about studies today is that participants sometimes aren't given results to lab tests until the study is over. This unethical practice will end with ALLRT. Viral load and other blood tests will be provided to the participant as they are performed. Other incentives, such as payment, have been discussed to encourage enrollment. Plans to store specimen samples are underway, which could provide crucial information down the line.

Obstacles

Since ALLRT is still in the planning stages, community members hope that the real intention of the study will remain intact after all the researchers have given their input. Because of past bureaucratic problems with the ACTG, many innovative ideas have been squelched by the changes made to a concept or protocol.

All of the technicalities involved in ALLRT may seem mind-boggling, and one may wonder how the ACTG can pull off such an inventive system given its limited resources.

Jacobson said, "To some extent, that is true. There are a limited amount of resources available to the ACTG. The intensity with which patients enrolled in ALLRT will be studied will probably lower the overall number of patients that can be enrolled in trials, but we think we can learn answers to more important questions in this way."

ALLRT should be in full swing by the end of the year, he said.

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