Dear Friends and Comrades
Below is a letter from TAC to Act Up Paris sent at the end of September 2006.
Our letter raised their irresponsible and unethical campaign against a key study of antiretroviral therapy in
Dear Friends and Comrades
Below is a letter from TAC to Act Up Paris sent at the end of September 2006.
Our letter raised their irresponsible and unethical campaign against a key study of antiretroviral therapy in Africa called the DART trial, which has been conducted in Uganda and in Zimbabwe. Their "reply" is also attached.
As you will see from the letter, we believe that Act Up Paris has made accusations against the trial and the researchers involved, which is either untrue or without evidence. Their unsubstantiated hysteria has undermined support for AIDS research and sowed unnecessary fear and suspicion about research among people living with HIV/AIDS across the world.
Our work as treatment activists must be based on evidence and data - we cannot advocate for AIDS treatment unless we understand and operate on rigorous principles of analysis based on hard facts.
We asked Act Up Paris to provide proof of their allegations against the DART study investigators and they have not done so in over two months' time. In fact, we know from others that members of the organization are traveling to Uganda this week to further spread misinformation about the study.
It seems that instead of addressing our concerns and those of others, Act Up Paris has decided to stealthily pursue its original campaign against the DART trial. We have no choice now but to make our letter to Act Up Paris public. TAC refuses any further interaction with the organization, as we see their work on AIDS treatment and clinical research to be based on willful misinformation and distortions of the truth which do a grave disservice to people living with AIDS.
As an organization with 20 000 registered members engaged in a struggle against unethical experimentation, HIV/AIDS denialism, government neglect and drug company profiteering we cannot work with ACT-UP Paris. We will not participate in any joint international work that includes ACT-Paris, any of their members, or, their front organizations in France.
TAC National Chairperson
TAC General Secretary
Act Up Paris
29 September 2006
By email and fax
CONCERN ABOUT ACT UP PARIS ACTIONS WITH REGARD TO DART TRIAL
We are writing to express our concern at Act Up Paris's actions with regard to the DART trial. We are all concerned that human medical trials should be conducted ethically. It is for this reason that the TAC regularly takes action against unethical experiments on people with HIV.
However, much research is conducted ethically. Such research is critical to improving the lives of people with HIV. Poorly conducted clinical trials must be criticised, but on the basis of legitimate allegations supported by evidence.
In August 2006, Act Up Paris led a demonstration at the International AIDS Conference in Toronto. The demonstration involved disrupting the speech of James Hakim, a researcher involved in a DART trial site in Zimbabwe. The protesters held up banners saying "Shame" while also demanding information about the deaths in the study information that has been readily available on the trial website since May 2006.Furthermore, on the ITPC and other email lists and in your own publications you have suggested that the scientists involved put trial participants at risk of illness and/or death and make other charges of improper conduct against the DART investigators. In particular, in your own pamphlet on the study you described the following issues as problematic:
Substandard information was provided to potential participants about the health risks involved;
The trial participants whose health declined rapidly under the investigational treatment were excluded from the offer in the consent form that they would get free optimal ARV treatment for at least five years;
DART investigators have chosen to conduct their study on HAART with no biological monitoring in clinics where such monitoring is available, thereby depriving clients who are recruited in the trial from optimal care to which they would otherwise have had access.
DART investigated, from the outset, a health situation which the scientific community universally described as dangerous: treatment interruptions for people with low nadir.
Low nadir patients were exposed to treatment interruptions without access to close “biological monitoring”, which you described as “even more dangerous”.
It was only 2 years after the initial launch of the trial that the investigators closed the treatment interruption arm (last March). We are unaware of any documentation that would support these claims:
---that the informed consent process did not offer adequate information to the participants on health risks associated with the study; and
---that any participants are excluded from the offer for post trial care.
We also believe your claims show that you either misunderstand or are willfully mischaracterizing some components of the study and the available research on structured treatment interruptions:
The DART study does not deprive any participant of laboratory monitoring of their HIV infection. The trial is an investigation of laboratory monitoring vs. clinical monitoring in the management of antiretroviral therapy to see what is the most effective strategy for use in resource poor settings where laboratory capacity is often minimal or non existent. However, participants in the “clinical monitoring” arm are indeed getting laboratory monitoring, except that the results are blinded for both the participant and their doctor until the study is concluded unless there are significant laboratory abnormalities that would require clinical intervention.
There is no correlation at all in the literature about low CD4 nadirs, structured treatment interruptions and increased risk of disease progression. In fact, SMART,the largest treatment interruption study conducted to date (>5,000 participants), found no association between CD4 nadir and the increased relative risk of progression and death that was seen among people taking long (~18 months) CD4 guided treatment interruptions. The 3 months on/3 months off structured treatment interruption arm in DART was associated with an increased risk of grade 4 events.
That's why it was stopped by the Data Safety Monitoring Board (DSMB). But it was not associated with an increased risk of death. It is not clear whether a low CD4 nadir predicted an increased risk of grade 4 events in the STI arm in DART. In the ongoing Trivacan STI study in Cote D'Ivoire, the CD4 guided arm was also stopped by the DSMB because of more grade 4 events compared to the continuous therapy arm and the 2 months off/4 months on STI arm (which is continuing).The factors that were associated with the increased risk of events were "a pre HAART concentration of HIV RNA in plasma of greater than 5 log10 copies per mL (p=0.03), and BMI of less than 20.5 kg/m2 at baseline." There was no association with CD4 nadir.
DART assessed the potential benefits of structured treatment interruptions in resource poor settings. The structured treatment interruption arm was stopped when a DSMB review showed more clinical events but not mortality in this arm compared to continuous therapy. The Act Up Paris pamphlet stated that there was a "1% death rate in the STI arm." This falsely suggests that there was excess mortality in the structured treatment interruption arm, when in fact there were 5/408 deaths in the STI arm and 4/405 deaths in the continuous therapy arm.
African scientists conduct their work under difficult circumstances for a number of reasons:
They have access to minimal research resources.
In some African countries a pseudo scientific view based on a distorted version of African nationalism is advocated that claims that African science should be conducted using different standards and methodologies to science elsewhere in the world. This view further marginalises African scientists and the TAC opposes it.
A commonly held racist view, both popularly and among scientists, is that African scientists are inferior to their counterparts elsewhere. Furthermore, AIDS denialists have attempted to derail critical antiretroviral trials, including the FTC trial held in South Africa and the HIVNET 012 trial in Uganda. Their efforts have been destructive and, but for the efforts of scientists and activists who have spent much time debunking their claims, almost resulted in setbacks to life saving programmes.
The DART trial includes a number of leading African scientists, including Peter Mugyenyi (who was also an early advocate for access to treatment for PLWHAs in Africa), Paula Munderi and James Hakim. The published results of the trial demonstrate a several fold decrease in mortality compared to historical controls. Furthermore, one purpose of the trial was to determine whether structured treatment interruptions were a viable option for people taking highly active antiretroviral treatment. This issue is of considerable importance to people with HIV throughout the world, but particularly in Africa, where structured treatment interruptions offered the possibility of more affordable regimens. It is unfortunate, based on data from the DART and SMART trials, amongst others, that structured treatment interruptions have been found to be disadvantageous. However, the DART study continues to give us key information on the use of antiretroviral therapy in Africa as was highlighted in several presentations at the recent Southern African HIV/AIDS Clinicians’ Society meeting in Botswana this month.
From all the published data and public evidence, it appears to us that there are no critical faults with the conduct of the DART trial and many of the claims you advance are either untrue, unsubstantiated or represent a misunderstanding of clinical research methodology and an inability to cogently analyse the existing data on structured treatment interruptions. Indeed, the trial demonstrated how effective HAART is at reducing mortality in resource poor settings and is offering additional information to guide clinicians and PWLHAs in the management of HIV disease here on our continent. Yet Act Up Paris has attempted to bring the DART researchers into disrepute. This has had the effect of undermining African scientists and continued research in Africa publicly funded research in particular. We have previously requested evidence from you to establish the basis of your claims against the DART trial. To date no such evidence has been made available. Nevertheless, you have galvanized other activists to support your campaign against this trial. You have justified this by stating in response to our request for your reasons for demonstrating against the DART researchers "people from Uganda are the ones to answer" (correspondence to N. Geffen, 28/8/2006).
We find this answer evasive and patronising. Act Up Paris has led the campaign against DART; it is for Act Up Paris to justify its reasons for doing this. We are not aware of any African organisations or individuals that have made allegations supported by evidence against the DART researchers. In this regard:
One of the putative trial participants who has made claims against the study, Max Ochira Olweny, is not registered as a participant in the trial. He was offered a meeting with the principal investigator in case he was using a pseudonym but he did not show for the meeting with Dr. Mugyenyi.
At a recent meeting in Kampala between member of the AIDS community and the trial investigators, no improper conduct was alleged by those in attendance, which included bona fide participants of the trial. In a report on that meeting by Ugandan activist Lydia Mungherera, trial participants held up their care in the DART study as a model for other treatment programmes in the country. We note that despite Act Up Paris's recent campaigns against various trials, your voice has been virtually silent in the campaign against Matthias Rath, who truly does conduct grossly unethical trials and whose head office is in the European Union, i.e. your area of influence.
We trust that since you have not presented your allegations or the evidence for them, you will have the courtesy to issue a public apology to the DART researchers whom you have embarrassed and whose reputations you have carelessly sullied. Alternatively, please present the evidence for your allegations without further delay. If Act Up Paris chooses neither of these options, or continues to present confused arguments as evidence, the TAC regrettably will have no reasonable choice but to end any future partnership with Act Up Paris.