Setting the Standard: New prevention trials in the era of oral PrEP

December 7, 2017

There’s a lot going on in the world of HIV prevention research right now. The HIV vaccine field has launched a second efficacy trial—HVTN 705/HPX 2008—investigating a mosaic vaccine that could protect against clades of HIV from around the world. HPTN 084, a second trial comparing injectable cabotegravir to oral PrEP as prevention, this one among women, also recently launched across Southern and East Africa. These two trials join five other efficacy trials currently looking to expand the range of new prevention options.

At AVAC, we came out with our annual AVAC Report on December 1–our attempt at trying to untangle the mixed messages that have been circulating, and offer solutions to confront them head on.

The report touches upon an issue that has gained a lot of attention: how participants might access oral PrEP as part of HIV prevention trials. In the midst of all this activity, we thought it necessary to dive deeper into this issue. It may seem simple: trial participants have the right to the highest standard of HIV prevention and care as part of participation. Both the WHO/UNAIDS ethics guidance and the UNAIDS/AVAC Good Participatory Practice Guidelines for biomedical HIV prevention trials clearly outline this point. But the ethics, trial design issues and the mechanisms by which interventions are provided as standard of care are quite complex. Opinions differ and politics abound.

On November 2-3, the South African Medical Research Council (SAMRC) held a summit in Cape Town to discuss this very issue of standard of care in prevention and treatment trials in Southern Africa. Before the summit, members of the Vaccine Advocacy Resource Group (VARG) convened an Imbizo—a South African term for a gathering led by a traditional leader to discuss policy issues—to develop their position on what standard of care should be in prevention trials, and the role that communities and advocates should have in these decisions. AVAC attended both the Imbizo and summit to support the VARG and engage in the discussions.

The topic and tensions–and, for the most part, the players—are not new. Standard of care, and particularly when and how to integrate new interventions into the prevention package, has been discussed and debated for nearly as long as the research itself. What is new is stakeholders across prevention research coming together to reach consensus on not only the package, but on how it should be delivered. Traditionally, these conversations have been siloed. Ethicists made decisions based on their guidelines, statisticians based on trial design considerations, researchers on national context and available resources. Excitingly, there is a way forward from the summit that integrates the different interests of a broad range stakeholders. This is Good Participatory Practice in action!

The summit arrived at some concrete next steps. The SAMRC and the Fred Hutchinson Cancer Research Center (FHCRC and home of the HIV Vaccine Trials Network) will establish a trial-agnostic fund to cover the cost of oral PrEP and HIV testing for HIV prevention trial participants for the duration of the trial; trial sites and their communities will decide how to provide PrEP at their site—and this will likely look different at different sites; sites will be encouraged to work with implementing partners to optimize PrEP access and to support adherence; and South Africa researchers will work with the National Department of Health’s (NDOH) PrEP Technical Working Group to support establishment of demonstration projects closer to trial sites.

These are commendable and essential steps—and advocates, AVAC included, will be following them closely. As we continue to reflect, these are the questions and issues that remain at the fore for AVAC.

How ‘standard’ can standard of care be?

Decisions about provision of oral PrEP in clinical trials as standard of prevention, in particular, are happening as PrEP is being rolled out with great variability in the very countries in which the trials are happening. This creates operational and ethical complications—as well as exciting opportunities. Is there undue incentive if participants are offered PrEP in the trial, but PrEP is not available in the communities? Are researchers filling for the role of government—which is responsible for setting and improving the national standards of care? Within the same country, South Africa being an example, availability of PrEP can differ even between trial sites, potentially creating inequality in how participants in the same trials and in the same country get access.

The consensus from the summit is that rigid standardization is likely impossible; community and trial context have to be taken into account. Some sites do not have the capacity to provide PrEP on site, while some do. Some are close in proximity to demonstration projects and implementation sites and can create efficient linkages, while others cannot. The agreement is that trial sites, in collaboration with communities and local and national advocates, will work together to define a model of provision that ensures all participants who want PrEP can access it. This variability presents an exciting opportunity for sites to be innovative, and for the field to learn from different models of PrEP provision in real time.

But researchers, regulators and communities must also monitor execution of the PrEP plans to ensure that variation does not lead to inequality in access—and stakeholders at all levels must be linked and coordinated so there is constant learning and more efficient collaboration.

How should coordination look different moving forward?

As we move from discussion to action, partnerships are a must. Meaningful coordination will be especially critical among:

  • Advocates and researchers: Civil society is key to the HIV response at national levels. They can, and should, play a concrete role in how to connect prevention programs to trials. As both the ethical guidance and the GPP guidelines highlight, advocates and civil society should have voice in these decisions, and it was good to see that happen in the summit. True engagement, though, doesn’t just mean one meeting. It means a comprehensive, transparent plan for the ongoing role for advocates.
  • Trial sites and governments: Science does not happen in a vacuum; national policies have great impact on trial conduct, and as we have seen with HVTN’s proactive and progressive stance with regards to treatment in HIV prevention trials in 2003—researchers can also have an impact on national policy. SAMRC has committed to working with the South African National Department of Health to set up demonstration projects closer to trial sites.
  • Trial sites and local and national PrEP implementation and research activities: If PrEP cannot be provided onsite, mechanisms must be developed to connect participants to PrEP delivery programs and initiatives. Data and existing capacity from the research and implementation activities should also inform messaging and enhance counseling and adherence support.
  • National advocates and community advisory boards (CABs): To ensure PrEP plans are developed with meaningful and inclusive engagement, that CABs need to be linked to national advocacy agendas, and national advocates, in turn, to the clinical trial objectives and activities. VARG members are planning to follow up with CABs and community engagement personnel to ensure coordination and synergy across sites and communities in South Africa.
  • Regulators, ethics review bodies and funders: The decisions from the summit stand to impact trials happening across Southern and East Africa and those being implemented by multiple clinical trial networks. To promote equity and ensure adherence to core ethical and scientific values, regulators, funders and ethicists need to be coordinated across geographies and networks.

So, what?

AVAC’s position, as we outlined in our new report, is clear: while one research organization, product developer or funder cannot reverse global inequities in HIV prevention or care, researchers have an obligation—and an opportunity—to try to narrow the equity gap. Trialists must grapple with PrEP provision in clinical trials head-on; they should work with program implementers and communities to develop, implement and assess high-quality prevention and treatment models for participants in research programs, and can encourage the development of sustainable community access to good quality, comprehensive HIV prevention.

The summit was a good starting place. As advocates we will be following the implementation of the plans set out by MRC and HVTN—we will be making sure that stakeholders involved and affected by the decisions (from advocates to regulators to trial site staff) are engaged in a sustained manner, that trial sites are communicating with PrEP programs in their contexts, and that there is equity in access across trial sites and across countries.

As we anticipate how the next generation of PrEP products and other HIV prevention modalities will further complicate standard of care conversations, it is partnerships and transparency that will make research smoother and more relevant to the real-world context.

Further resources