A significant proportion of people living with HIV would be willing to take part in a study towards a cure for HIV infection, as 21ª International AIDS Conference (AIDS 2016) in Durban, South Africa last month.
However some potential participants may not fully understand that taking part in an early phase of a study is highly unlikely to lead to any personal clinical benefit but may have the potential to cause serious harm.
"There is an ethical imperative to understand the motivations of decision-making, expectations and understanding of potential trial participants," researchers say. Better commitment to community and education seems necessary.
According to an Australian study, 82% of people living with HIV would be "willing" or "very willing" to participate in a clinical trial related to a cure for HIV infection. However the respondents would be less willing to participate if they knew that:
- They would increase their susceptibility to disease (87%),
- They risked developing cross-resistance to existing antiretroviral (79) chains.
- It resulted in an unpredictable increase in viral load for up to one year (63%), or
- They would be committed to the need for weekly visits to a medical clinic for several months (40%).
In contrast, 31% would be more willing to participate if it would help future generations but offer no personal benefits.
When questioned about the possible characteristics or benefits of a cure, respondents indicated that the most important thing was not to pass the virus on to others. It is also very important not to be at risk of ill-health due to advanced HIV disease.
Other results were classified as inferior: stopping the use of antiretroviral drugs, being considered a person without HIV infection, not contracting HIV again for a second (editor's note recontamination can be disastrous in a successful treatment because it can bring strains resistant to that therapeutic scheme ) and less medical visits.
More detailed conclusions came from a questionnaire filled out by 400 Americans living with HIV, 77% of whom were male sex. Considering that 65% were white, 17% black, 12% hispanic, 4% mixed and 2% of Asians. Along with the research, interviews were conducted with 36 people living with HIV, physicians, researchers, bioethicists and regulators. The results were reported in a series of posters.
Considering data that came from Australia from a general survey among HIV-positive people covering a wide range of issues, in the American participants were connected to research networks for the cure of HIV were recruited for a survey on this cure. They could expect to be better informed about healing issues and more interested in participating in a healing study.
Despite this, 8% believe that the cure for HIV already exists. More than 27% think that the cure will likely be available within five years and 33% think they would still have to wait for another ten years. (The author of this blog reserves for himself the right to say that he does not think about healing and that he lives one day at a time and, in contradiction, makes plans twenty-five years in the future ...)
Asked about the potential benefits of taking part in healing-related research, the benefits to society as a whole were highly classified. Helping to find a cure for HIV (95%), helping others with HIV in the future (90%) and contributing to scientific knowledge (88%) were among the most cited reasons.
There and besocial benefits could have an emotional impact - "the pleasant feeling of having contributed in one way or another to research for the cure of HIV" was a significant personal benefit (80%). Respondents also hoped to gain knowledge about their own health or about HIV (78%) and new treatment options (77%). Getting better access to medical care was cited by a number of participants, but few were motivated by financial compensation.
In terms of clinical benefits, many respondents expressed the wish that they can increase the capacity of their immune system to fight the HIV virus (92%), reduce the HIV reservoir in their body (85%), charge control (84%) or reduce the risk of transmission of the virus to a sexual partner (79%).
However the researchers commented that the "early phase of research does not confer directly projected clinical benefits and there is a possibility of damage as medical knowledge advances."
Research has shown that participants are less aware of risks than of benefits. Inquiring about the potential risks that would dissuade them from participating in a study related to HIV cure, respondents indicated a number of possible damages but fewer.
In terms of clinical risks, increased risk of cancer (49%), development of antiretroviral drug resistance (37%), side effects (30%) and known risks of stopping anti-HIV drugs (30%) could discourage participation.
Study procedures presenting the greatest obstacles were lumbar punctures (26%), bone marrow biopsies (22%), lymph node biopsies (13%) and rectal biopsies (13%). Specific side effects such as hair loss (32%) and vomiting (23%) would be a reason to quit. Practical problems such as ambulatory failure parking (20%) or obtaining transportation (17%) could also discourage participation in a study.
A small group of people living with HIV were interviewed and asked what is "too much risk" to participate. Some of his answers were:
"Try a never-tested approach on humans."
"Genetic manipulations that could result in cancer would probably be the most frightening and unbearable."
"If I were to become resistant to the drugs that are saving my life in the present."
"A risk that would have taken my health to an irreversibly worse situation than I am now."
"Death risk greater than 1%".
The doctors and researchers who were interviewed also had opinions on what would pose a "very high" risk. Most said that unhealthy stem cell transplants in non-cancerous or stable participants with suppressed viral load in antiretroviral therapy would be too risky. Another mentioned was the protein-1 anti-programmed cell death (cell apoptosis) which has shown significant toxicities in animal studies.
Similarly, regulators who were interviewed said that some studies were too risky to pursue. If there were insufficient data to assess the risk or the potential insufficient benefits with regard to overcoming the risks, approval is not given. A poorly designed study would be unable to bring us closer to a cure, although the participants' exposure to risk.
A specific study with the procedure that could expose participants to harm is a treatment with an analytical disruption. Stopping antiretroviral treatment in order to evaluate the time of viral rebound or rebound predictors is also a factor of refusal. Of the respondents, 26% reported that they were very willing to this and 42% very unwilling to discontinue their treatment.
During the interviews, motivations to be included by a desire to help find a cure ("Knowing that you are a part of something that can help many people in the future"), past experiences with treatment interruptions ("They left me without the drugs for three years, and within three years my CD4 count never dropped below 550.")
And financial benefits ("It would be less expensive not to have to take medicine for 6 months") Translator's note. Not all countries offer treatment and bear the financial costs of a treatment against AIDS is something that challenges the most solid of family assets, arriving, as many have arrived, at bankruptcy, and then there was no continuity solution for the treatment and the rest ... each one can imagine for itself ...
But other participants saw a discontinuation of treatment as something that would be "too risky." They were concerned because they could feel an increase in viral load, could transmit HIV, develop resistance or could have opportunistic infections.
Given some of the misconceptions and concerns that emerged from the study, American researchers said that more comprehensive education and stakeholder engagement are needed. They make a large number of recommendations including:
- People living with HIV should be engaged early in HIV cure research using guidelines for good participatory practice (BPP).
- Transparency about research objectives, processes, and expected outcomes is crucial to countering rumors and setting realistic expectations for the early phase of research.
- Researchers have an ethical duty to inform risk to potential study participants and to explain the lack of expected clinical benefits.
- Participants in HIV cure research should know that interventions are experiments that assess basic safety and are designed to generate knowledge for the benefit of society.
- The perception that it constitutes a "too much risk" should be taken into account when preparing and approving studies; there should be safeguards to protect participants from taking unacceptable risks.
- Risks assumed by study participants should be minimized and reasonable in relation to the importance of scientific research and the knowledge that can be generated.
- Treatment fatigue should not be used as a way to attract volunteers for studies involving an analytical discontinuation treatment.
- Posted in: 31 August 2016
- Translated by Claudio Souza of the origin in Realism needed about the benefits and risks of taking part in HIV cure studies
- reviewed by Mara Macedo
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Salzwedel J et al. Involvement with the community in research related to HIV cure: applying good participatory practice (GPP) principles to community education efforts. XXI International AIDS Conference, Durban, summary THPDD0102, 2016.
Sylla L et al. Perceived benefits of HIV cure research related to participation in the United States. XXI International AIDS Conference, Durban, abstract WEPED308, 2016.
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Dubé K et al. What is "too much risk" in the cure of HIV clinical research in the United States? XXI International AIDS Conference, Durban, abstract THPEB076, 2016.
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