IAPAC Summit - If people who need HIV drugs aren’t getting them now, why should the prevention benefit of treatment be the reason that the drugs become available?

via Aidsmap, by Roger Pebody

The issue of ‘treatment as prevention’ raises a number of ethical issues, Richard Ashcroft, professor of bioethics at Queen Mary University of London told the IAPAC Controlling the HIV Pandemic with Antiretrovirals Evidence Summit in London this week.

He reminded the audience that it is rare for a doctor to give a patient a medicine that will primarily benefit a third party. He went on to highlight situations in which, at present, antiretroviral treatment is not universally available to all people who need it for their own health. In such circumstances, why should treatment’s prevention benefit be “the clincher” that convinces funders and policy makers to make the drugs more widely available?

At the same meeting, Kevin Fisher of AVAC noted that the ethical concerns tended to differ in different parts of the world. In settings where there is already good access to HIV treatment, the concerns are often related to individuals experiencing external pressure or compulsion to take treatment. In resource-limited settings, the concerns focused more on the cost of and access to treatment.

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And check out the Mapping Pathways slides that were presented at the same meeting, on the issue of PrEP.

[Content that is linked from other sources is for informational purposes and should not construe a Mapping Pathways position. Please look for us on Facebook here www.facebook.com/MappingPathways and you can follow us on Twitter @mappingpathways as well.]

Ethical Concerns Raised: Human Experimention Without Subject's Consent

viaNature.com by Matthew Walter

The injections came without warning or explanation. As a low-ranking soldier in the Guatemalan army in 1948, Federico Ramos was preparing for weekend leave one Friday when he was ordered to report to a clinic run by US doctors.

Ramos walked to the medical station, where he was given an injection in his right arm and told to return for another after his leave. As compensation, Ramos's commanding officer gave him a few coins to spend on prostitutes. The same thing happened several times during the early months of Ramos's two years of military service. He believes that the doctors were deliberately infecting him with venereal disease.

Now 87 years old, Ramos says that he has suffered for most of his life from the effects of those injections. After leaving the army, he returned to his family's remote village, on a steep mountain slope northeast of Guatemala City. Even today, Las Escaleras has no electricity or easy access to medical attention. It wasn't until he was 40, nearly two decades after the injections, that Ramos saw a doctor and was diagnosed with syphilis and gonorrhoea. He couldn't pay for medication.

“For a lack of resources, I was here, trying to cure myself,” says Ramos. “Thanks to God, I would feel some relief one year, but it would come back.” Over the decades, he has endured bouts of pain and bleeding while urinating, and he passed the infection onto his wife and his children, he told Nature last month in an interview at his home.

Ramos's son, Benjamin, says that he has endured lifelong symptoms, such as irritation in his genitals, and that his sister was born with cankers on her head, which led to hair loss. Ramos and his children blame the United States for their decades of suffering from venereal disease. “This was an American experiment to see if it caused harm to human beings,” says Benjamin.

Ramos is one of a handful of survivors from US experiments on ways to control sexually transmitted diseases (STDs) that ran in semi-secrecy in Guatemala from July 1946 to December 1948. US government researchers and their Guatemalan colleagues experimented without consent on more than 5,000 Guatemalan soldiers, prisoners, people with psychiatric disorders, orphans and prostitutes. The investigators exposed 1,308 adults to syphilis, gonorrhoea or chancroid, in some cases using prostitutes to infect prisoners and soldiers. After the experiments were uncovered in 2010, Ramos and others sued the US government, and US President Barack Obama issued a formal apology. Obama also asked a panel of bioethics advisers to investigate, and to determine whether current standards adequately protect participants in clinical research supported by the US government.

When details of the Guatemalan experiments came to light, US health officials condemned them as 'repugnant' and 'abhorrent'. Last September, the Presidential Commission for the Study of Bioethical Issues went further, concluding in its report1, that “the Guatemala experiments involved unconscionable violations of ethics, even as judged against the researchers' own understanding of the practices and requirements of medical ethics of the day”

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[Content that is linked from other sources is for informational purposes and should not construe a Mapping Pathways position.]

Because We Can: Clashes of Perspective Over Researcher Obligation in the Failed PrEP Trials

via Developing World Bioethics, by Bridget G. Haire

Abstract

This article examines the relationship between bioethics and the therapeutic standards in HIV prevention research in the developing world, focusing on the closure of the pre-exposure prophylaxis (PrEP) trials in the early 2000s. I situate the PrEP trials in the historical context of the vertical transmission debates of the 1990s, where there was protracted debate over the use of placebos despite the existence of a proven intervention. I then discuss the dramatic improvement in the clinical management of HIV and the treatment access movement, and consider how these contexts have influenced research practice. I argue that as HIV prevention trials oblige researchers to observe the rate at which vulnerable people under their care acquire HIV, there is an obligation to provide antiretroviral treatment to seroconverters and other health care benefits that fall within the scope of researchers’ entrustment, both to avoid exploitation and to enact reciprocal
justice. I argue against propositions that the obligations to provide specific benefits are vague, fall only upon researchers and sponsors, and create injustices by privileging the few over the many. Finally, I contend that the realisation of a broader standard of care in HIV prevention research broadens the role of research from being a simple tool to produce knowledge to a complex intervention that can play a part in the reduction of health disparities.

Read the full paper here.


[Content that is linked from other sources is for informational purposes and should not construe a Mapping Pathways position.]

What Happens When the "Placebo Window" Closes?

With the increasing number of trials pointing to the efficacy of PrEP and microbocides as methods of possibly preventing the risk of HIV infection, the ethics of using placebos in these trials is becoming a topic of discussion among the prevention community. We spoke with Joseph Romano, who has been involved with HIV/AIDS research and development for 20 years, about his thoughts on placebo-controlled trials, the “placebo window,” and what happens in a post-placebo era.

MP: Why do we have placebo-controlled trials?

Joseph Romano: Placebo controlled trials are essential for the evaluation of the safety and efficacy of new products.  The placebo control group in a clinical trial provides the means of establishing any specific safety issues with a product, as well as the effectiveness of the product at preventing HIV transmission.  In terms of determining efficacy in microbicide studies, or in studies of other HIV prevention products, the trials are set up so that one group receives the treatment product and the other group uses the placebo product.  The number of participants in each group that is necessary to establish the effectiveness of a product with a high degree of certainty can be calculated, and this establishes the size of the trial population.  At the end of the study, the number of seroconversions in each group is established and a mathematical comparison between the two groups is conducted.  If the number of new infections in the treatment group is lower than the number in the placebo group such that a predetermined statistical threshold is met, the drug can be defined as effective with a certain level of certainty.  This type of calculation would not be possible without the placebo group in the trial. 

MP: What do we learn by including placebos? 

Joseph Romano: The placebo group is necessary to establish the safety of a product.  Even if a product is shown to be highly effective relative to a placebo, the product cannot be used if it also produces a significant number of side effects or adverse events relative to the placebo group.  In the case of HIV prevention products like microbicides, the importance of the placebo group to establishing safety goes beyond adverse events.  The people who will use these products are HIV negative.  Thus, it is crucial to show that the use of these products in no way enhances the potential for acquiring an HIV infection during the course of the trial.  One of the very early clinical trials of an N-9 based microbicide product demonstrated that use of this product led to an enhanced risk of HIV infection relative to people who used the placebo.  This was particularly important since the product used in this study was present in many over the counter products.  Thus, the placebo control not only served to show that this product could not protect against HIV infection, it was also the means by which this product was shown to have an increased risk of enhancing HIV infection.  The placebo control also allows for comparisons to be made during the course of the trial, prior to its completion.  Most trials are designed to have blinded review of the data from the treatment and placebo groups during the course of the study.  Again, by using certain calculations, it can be determined whether or not a product will likely be shown to be effective in a trial based on the analysis of data obtained partially through a study.  If these types of interim evaluations of a product relative to placebo show that it is highly unlikely for a product to be effective against HIV transmission by the end of the study, a trial can be stopped.  This early termination of a trail will obviously save significant amounts of money and resources, but more importantly, it will prevent continued experimentation in subjects with a product that is not likely to be of any benefit.  This use of the placebo group has been used to stop a number of HIV prevention trials, including specific microbicide trials.

MP: What is meant by the term “placebo window?”

Joseph Romano: The “placebo window” refers to the time period during which it will be feasible to conduct placebo controlled efficacy studies.  This period typically exists during the time when approved products for the intended indication are not yet available. Currently, there are no approved microbicide products available for HIV prevention.  Consequently, there is no established “standard of care” for this indication.  Without an established way of providing people with a product that is known to work for the indication, it is ethical to use placebo controlled trials since the placebo should provide no additional risk relative to people who are not part of the trials.  However, once a microbicide product has been adequately shown to prevent HIV infection, there will then be a standard of care available that provides more protection to people using that product, as opposed to people who would use a placebo.  With the availability of a product with well-established efficacy, it would then be unethical to enroll people into studies that involve a placebo product since people receiving the placebo product would essentially be denied access to something that affords some level of protection.  So, once a microbicide product has been adequately shown to prevent HIV transmission, it will no longer be possible to run placebo controlled trials, and the “window” will be closed.  It may even be the case that once any HIV prevention strategy is shown to prevent HIV transmission, it will be necessary to use that effective strategy in a trial designed to evaluate an alternative prevention strategy.  For example, if an oral PrEP strategy is shown to be effective at preventing HIV transmission before an effective microbicide product is available, it may be necessary to run future microbicide studies in comparison to the oral PrEP product. 

MP: Is the field adequately prepared for the day when the placebo window closes?  What needs to be done to prepare? And how will it be decided when that day comes? Who gets to decide? 

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