Activists demand new research agenda.

Community consensus statement sent to NIH 

Meeting in San Francisco on January 29, 2000, activists from across the nation undertook a day-long discussion of the need for research into the long-term effectiveness of antiretroviral therapies. This meeting followed a National Institute of Allergy and Infectious Diseases (NIAID) workshop in Bethesda entitled "Long-term clinical studies in HIV infection." The purpose of the San Francisco gathering was to update treatment advocates on the results of that workshop and to elicit discussion on the need for and the feasibility of 3 potential studies aimed at answering these questions:

When should patients start antiretroviral therapy?

When should patients change a failing antiretroviral regimen?

What is the long-term clinical efficacy and tolerability of antiretroviral therapy?

Based on these considerations, the following consensus statement was written and sent to the National Institutes of Health (NIH). Over 20 organizations and approximately 50 community activists endorsed the statement. The NIH recently approved funding for the SMART study, a long-term clinical endpoint study that will focus on the use of antiretroviral therapy in the treatment of HIV disease. While SMART cannot answer all the questions mentioned in the consensus statement, it is the first NIH-approved study that addresses some of these issues. We hope that others will soon follow.

Consensus Statement on Long-term Effectiveness Research

1. Too Many Questions, Not Enough Answers: The Urgent Need for Long-Term Effectiveness Research

Every day thousands of people living with HIV agonize over questions about whether or not to begin antiretroviral therapy:

* How high can my viral load rise or my CD4 count fall before it's too late? How safe are the medications?

* If I start now, will the drug complications and toxicities outweigh the benefits?

* Should I wait for newer and better medications?

* How long can I afford to wait?

* Which is the best drug regimen to start with?

And, along with almost everyone already on antiretrovirals, they worry about drug complications and resistance.

* What are the long-term complications and toxicities?

* What are my chances of getting them?

* If the drug regimen doesn't work or stops working, what should I do next?

* How long before I develop resistance to the drugs?

* How high can I let my viral load climb before I need to change drugs?

* What should I do when multidrug resistance develops?

Are the answers to these questions different for women and men? For different ethnicities? For different age groups? How about those with additional diseases, such as hepatitis, diabetes, cardiovascular disease, or addiction disorders?

These are issues that will affect the lives and health of hundreds of thousands of people, involve billions of dollars in annual medication and other health care costs, and influence the standards of HIV care for decades.

Yet there is precious little scientific data to help us make these decisions.

We, the undersigned, call on the National Institutes of Health to address this situation immediately.

NIH must immediately commit significant financial and organizational resources to research these questions and develop, as expeditiously as possible, a detailed plan for that research. We are years behind where we should be and the lives and health of many are increasingly at risk.

As a first step in this process, NIH should immediately consult with a variety of advisors--including members of the HIV/AIDS community, researchers, clinicians, statisticians, and members of the pharmaceutical industry--to begin development of a long-term clinical research plan.

We insist upon full and immediate community participation in all stages of planning this research, utilizing the experience, knowledge, and commitment of HIV/AIDS community activists reporting back to the larger affected community.

2. Priority Areas for Long-Term Effectiveness Research

We call on NIH to demonstrate leadership and expedite the design and funding of long-term effectiveness research to answer these priority questions:

* When and how should antiretroviral therapy be started?

* When should antiretroviral therapy be changed and to what?

* What are the long-term complications and toxicities of antiretroviral therapy?

* What are the consequences of moderately unsuppressed viral load and treatment interruption?

It is important that the answers are relevant to as many people living with HIV as possible including women, the elderly, adolescents, African Americans, Hispanics, and other ethnic groups, as well as those living with hepatitis, diabetes, or other life-complications.

3. Design of Long-Term Effectiveness Research

NIH must confront its institutional biases and restrictions and provide creative, collaborative, and flexible leadership in conducting trials that will certainly be larger and longer than those it has traditionally conducted for HIV/AIDS.

* NIH should consult a wide range of experts, including those who have done long-term research in other fields of medicine.

* The NIAID funding cycle is currently 5 years. NIH needs to ensure that there is adequate funding for the longer time periods required to complete these kinds of studies.

* NIH must demonstrate leadership to begin collaboration among national and international HIV research networks and to secure the cooperation and participation of the pharmaceutical industry. The well being of those living with HIV must supersede personal and institutional agendas and in-fighting.

* NIH should give priority to trial designs that permit analysis according to the subpopulations we have highlighted--whether by stratification, nested substudies, or other appropriate trial design.

* The landscape of antiretroviral therapy is constantly changing. Trial designs must be flexible to accommodate new developments and ensure the relevance of answers at the conclusion.

* The length and size of these studies, as well as the great importance of the answers for determining proper standards of care for HIV treatment, require extraordinary efforts for recruitment and retention.

* NIH needs to conduct educational campaigns, targeted at patients and providers, to aid in the recruitment and retention of people from all affected communities.

* Trials should be conducted in the settings in which patients receive their regular medical care.

* The complexity of these trials may require assessments of their feasibility, including pilot studies.

Not every question may require a randomized clinical trial. Some, such as the elucidation of long-term complications and toxicities of antiretroviral therapy, may be better answered with observational databases.

Yet, NIH is ultimately responsible for guaranteeing that these questions will be answered in an efficient, ethical, and scientifically rigorous manner.

Too much time has already been lost. The risk of continued delay is too great. We call on NIH to act now.