Can new ethical guidelines reshape HIV prevention trials?

In a bid to include ethical considerations in the HIV prevention trial process UNAIDS and the World Health Organisation recently launched a new guidance document for ethical consideration for HIV prevention trials. The guidance among other things, calls for the inclusion of communities that live in settings where trials are taking place as equal partners.

Researchers believe that when communities are actively involved in a study, especially at the early planning stages, interests of members of the communities would be prioritized, rights of the participants would be ensured, conducts would be agreed upon, and post-study arrangements would be sorted out even before the commencement of the studies.

Speaking at the unveiling of the new guidance at the recently held HIV Research for Prevention Virtual Conference, Dr. Soumya Swaminathan, WHO’s chief scientist admitted that complex ethical challenges exist at the heart of all biomedical research and this is more apparent in HIV prevention research.

“Today, some of the specific issues of concern include the standard of care and prevention, the risks and benefits to both research participants and their communities and informed consent. We can see parallels of this today in the pandemic and the clinical trials that are going on across the world,” she said.

Despite the noble goals set out in the guidelines, some researchers say that the document may better serve an aspirational goal on what should be ideal as it is currently unenforceable and would require significant changes in the design process of HIV prevention trials. 

Reimagining fairness and vulnerability

Even though attention is now increasingly being drawn to countries where inequalities are limiting access to HIV/AIDS treatment and prevention programs, it has not been regarded as a major issue in HIV clinical trials, until now.

The new guidance noted that studies need to ensure fairness and inclusive selection of study populations. It further advised against excluding study participants because of their age, pregnancy, gender identity, or drug use.

In a similar vein, it presented a redefinition of the term “vulnerable” noting that the term may be considered as derogatory and people and groups should not be labeled as vulnerable. Instead, emphasis should be on the social or political contexts in which people live that may render them vulnerable.

In addition, the report also brought attention to the fluid nature of vulnerability as individuals may live in more than one context of vulnerability, including the criminalization of drug use and sex work, homophobia, and housing instability.

The guidance urged HIV clinical trial study designers to also put the harm which study participants may be exposed to into consideration, noting that participation in HIV prevention trials has complex implications that may exacerbate potential harms, for example, through inadvertent disclosure of activities criminalized by the state.

High hopes

Peter Godfrey-Faussett, UNAIDS science adviser, said with the revised guidance, stakeholders in HIV clinical trials will now receive support in designing and conducting ethically and scientifically sound HIV prevention trials that advance the AIDS response toward the goal of zero new HIV infections.

Drawing attention to specific key issues in HIV research, Daisy Ouya, communication adviser at the AIDS Vaccine Advocacy Coalition, said the guidance will also become an effective tool for advocacy. She noted that the new guidance will be integrated into regular consultations and research engagement training for civil society, as well as HIV prevention advocates.

She added that it goes hand in hand with good participatory practice for clinical trials and that her organization will be conducting a research engagement series that will focus on the new HIV prevention trials with novel trial designs.

“The implementation of the new ethical guidance, by all stakeholders, will foster ethical, efficient, credible, as well as acceptable research that will deliver the next generation of HIV prevention methods and products for the world,” she added.

Confronting reality

While noting that several aspects of the guidance are well intended, a number of HIV researchers noted that the document would better serve an aspirational goal on what should be ideal instead of directly dictating how things will be done henceforth.

Roger Tatoud, deputy director of HIV programs and advocacy at the International AIDS Society noted that there is an ethical challenge about how resources are allocated for public health good and “this can sometimes be in tension with the very strong Helsinki Declaration on ethics.”

He added that there are particular challenges with vaccine trials and other HIV prevention tools where the researchers are interested not only in whether the product works but also in the durability of any protection that is gotten.

“So, at what stage does one stop a trial to give participants in the control group the benefits?” he asked.

From a local HIV research perspective, Nigerian public health doctoral candidate, Bayo Akinbile noted that the guidance has a slim chance of directly influencing how small cohort studies on HIV are conducted. He argued that getting HIV researchers to comply with the guidelines would entail getting the ethical review committees on board.

According to him, mandating that the requirements be followed is the only way to achieve the desired changes in the clinical trials as the guidance may have little or no direct influence on primary investigators whose HIV studies are not directly sponsored by an organization that would direct its grantees to abide by the new guidelines.

“I think it’s only the major HIV clinical trial sponsors and multinational organizations that can willingly comply with the additional requirements. As it is presently, the guidance is just a suggestion and there is no mandate to make it compulsory for everyone to abide by. This is where the ethical review committee comes in,” he said.

He noted that while getting community members involved in a study from the outset is noble, it would require a paradigm shift in HIV research considering study designs are usually complete before communities are approached.

But in spite of the limitations, Tatoud said the need for new prevention tools for HIV showed research will continue to be carried out and they need to be ethically conducted.