A community meeting, Long-Term Effectiveness Clinical Trials in HIV/AIDS, met in San Francisco on January 29, 2000, the day before the Retrovirus Conference began. Approximately 50 activists met in response to the NIH's workshop on long-term studies in HIV infection that was held in Bethesda on January 12 and 13. The NIH workshop addressed the following questions: What are the high priority clinical questions to be addressed through long-term clinical studies in the era of HAART? What is the role of cohort studies and randomized clinical trials in addressing long-term clinical questions? What are the statistical challenges and alternative approaches in addressing long-term clinical questions? There were also breakout sessions on when to start, when to switch, and long-term clinical efficacy and tolerability of HAART.
Participants of the NIH workshop provided summaries and led discussions of how the HIV/AIDS community should respond. As might be expected, everyone agreed that data on long-term treatment of HIV/AIDS -- including information about toxicities and side effects, quality of life, treatment strategies (especially when to start and when to switch), and coinfections -- would be valuable. However, there was less consensus when it came to logistics. For instance, which questions would require large, randomized trials, and how large would they have to be? What role could observational studies play? Would changes in treatment make the results obsolete? How difficult would it be to enroll participants? What should the clinical endpoints be? Ethical concerns about equipoise, determining the standard of care, and informed consent were also raised, as was the importance of getting input from a more diverse and representative group. Some, however, felt that money would be better spent on smaller trials focusing on more specific questions.
Since this meeting, a Long-Term Effectiveness Research (LTER) Focus Group has formed to address these and other issues. It has issued the following consensus statement, which GMHC and a large number of other organizations have signed.
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 multi-drug 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 five 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.
Back to the GMHC Treatment Issues Spring 2000 contents page.