Refining the HIV clinical trials enterprise

New opportunities for innovation and discovery in HIV research are within our grasp. By 2020, the National Institutes of Health will refine its science-driven HIV clinical trials enterprise to deliver the innovative, efficient results needed to turn the corner on the HIV/AIDS pandemic.

Every 7 years, NIH competitively renews its funding of the HIV clinical trials networks operating in the United States and internationally. NIH began this renewal process in 2017, embarking on conversations with stakeholders and the research community to define the questions that will drive the next wave of HIV treatment and prevention innovation, and set in motion the process by which we may seek answers to those questions. These conversations have helped shape the focus and priorities of NIH’s HIV clinical trial networks through 2027.

In January 2019, NIH released six Funding Opportunity Announcements (FOAs) inviting proposals on HIV prevention, therapeutic, and vaccine networks; laboratory centers; and statistical and data management centers. A FOA for HIV clinical trial units is planned.

Learn more about the FOAs and the network refinement process with the resources and information available on this site. The following resources may be of particular interest to potential applicants:

For information about the refinement of the HIV clinical trials enterprise, view background>, videos and blog posts.

Don’t Miss These New Resources on

Happy New Year! We hope that you started your year refreshed for important work ahead–and to help get you started, we’ve rounded up a few select resources from that we hope you’ll consider as you set your agenda for 2019. We think these cross-cutting and thought-provoking tools help to frame the most pressing issues facing HIV prevention in the year ahead.

Px Wire: 10 questions for 2019
The final Px Wire of 2018 lays out 10 questions on issues confronting the HIV prevention field. We raise questions and offer brief analysis of: NIH funding and the future of research on user-initiated prevention options; anticipated results from the ECHO and DISCOVER trials; how programs and policies for rolling out oral PrEP—and possibly the dapivirine vaginal ring—need to evolve; how condom programming should be prioritized, and so much more. The centerspread features an infographic linking the timeline of prevention research with the pace that’s needed for implementation.

Next-Generation Trial Design
Has HIV prevention research seen its last placebo-controlled efficacy trial? As trials become increasingly complex, researchers are exploring how to continue to successfully study new strategies. AVAC has two new resources to help you understand the issue and the implications for advocacy and stakeholder engagement.

amfAR’s new database on PEPFAR
The PEPFAR Monitoring, Evaluation and Reporting (MER) Database, is a new web tool created as part of the COMPASS Africa collaboration. It gives HIV advocates access to a wide range of PEPFAR program data, such as district-level data with descriptions of what each indicator means, how the results are measured, and how the data can be interpreted. These data are presented in a variety of formats including data visualization, maps and downloadable PDFs.

Special Supplement on GPP
In October, the Journal of the International AIDS Society published a special supplement, Science, Theory and Practice of Engaged Research: Good Participatory Practice and beyond. It documents good participatory practices and explores their value to stakeholder engagement at clinical trials across research areas, geographies and populations. You might also like how one of the authors of the JIAS supplement laid out the issues in this piece, cross-posted on AVAC’s blog, P-Values.

Women Need Effective Choices: Do research dollars reflect this priority?
A growing number of voices are recognizing the importance of choice in HIV prevention – including a year-beginning statement from Maureen Goodenow, the Director of the Office of AIDS Research at the National Institutes of Health. The need for better choices is especially imperative for women who carry a disproportionate burden of HIV risk compared to men. The Resource Tracking for HIV Prevention R&D Working Group’s annual report looks closely at investment trends and features an infographic depicting the status of 2017 investment in research investigating PrEP for women.

Young Women Demand Inclusion
The best way to understand the diverse needs of those who face a risk of HIV is to listen to the people themselves. At the HIV Research for Prevention conference in Madrid in October, a group from the Young Women’s Leadership Initiative organized a protest to demand their inclusion in the process of planning for research. Read their statement, get inspired and heed the call in your work in 2019!

Sharpening the Blunt GPP Instrument: A call for focused stakeholder engagement in designing the efficacy trials of the future

Stacey Hannah is AVAC’s Director of Research Engagement. Ruth Assefa is an AVAC consultant, aspiring medical student and formerly AVAC’s program coordinator for research engagement.

Is HIV prevention research seeing its last placebo-controlled efficacy trials? Will the field have to radically reimagine how to answer efficacy questions?

HIV prevention research is indeed set to see changes in clinical trial conduct. Successes in research and implementation are making it easier for many people across the globe to protect themselves from HIV—and, at the same time, harder for researchers to test new interventions. Trials of the future might be bigger, more expensive, and require new types of analysis. As researchers and regulators navigate this territory, they’ve made a call for community input. Attendees recently heard this call at HIV Prevention Efficacy Trial Designs of the Future, a symposium convened by a group of leaders in prevention research in November to discuss new approaches to trial design.

With equations, statistical models, and new trial-design concepts, these were complex conversations indeed. And community input did have a place at the symposium. Jeremiah Johnson of the Treatment Action Group gave a plenary articulating the priorities of some communities, and the day’s panel discussions each included a community representative.

It was a good start, but only a start. As Jeremiah made sure to say, a white, cis-gendered man can’t represent all communities who will be affected by new and complex trials in HIV prevention research.

At AVAC, we’ve given a lot of thought to how to sharpen implementation of the guidelines on Good Participatory Practice to get the field beyond the mere rhetoric of community engagement and towards a strategy-driven engagement of stakeholders. A critical first step for researchers and civil society alike is to define the ongoing role community representatives will have as issues arise from evolving trial design. Will engagement focus narrowly on securing broad support for trials—or something more? (We hope the latter.) Specific objectives of engagement will certainly develop and change with the issues, but they need to be articulated clearly and planned for accordingly. And this should be a two-way street. Those who lead trials have a duty to articulate what they need and want from affected communities and stakeholders, but those stakeholders have an equal duty to probe the issues and articulate their priorities.

What should advocates be thinking about now to prepare for this issue in 2019? For some time, prevention researchers have discussed the possibility of screening trial participants before randomization to identify individuals who may be more or less able to use a given product. Some years ago, microbicides researchers actively explored the idea of screening cis-gender women after enrollment and before randomization to identify those likely to be adherent to a product, since low use can return a low-efficacy result that doesn’t reflect the actual prevention benefit of a product.

Now the question is whether it is feasible, acceptable and ethical to randomize participants who are low adherers, or who don’t want to use a daily product like tenofovir-based oral PrEP, into a trial arm where daily oral PrEP wouldn’t be a part of the control arm. (In all trials, all participants should be provided with a comprehensive prevention package that includes the offer of or referral for PrEP wherever it is available; even in these trials, all participants would be free to choose PrEP on their own. For a lexicon on emerging issues in HIV prevention trials, checkout AVAC’s HIV Prevention Trial Terms: An advocate’s guide.) Communities and advocates will have critical and unique insights into whether affected communities might support such a design–or whether it might provoke controversy—and how such a trial might be implemented.

Discussions and decisions should be as locally relevant as possible, and one can expect they will be moving to Southern and East Africa, where a bulk of these new, innovative trials for next-generation products will happen. HIV-focused civil society networks at country and regional levels need to be involved with trial leaders, product developers, statistician and ethicists in providing input and engaging constituents about these and other issues.

Check out our most recent podcast episode on Px Pulse for an in depth discussion exploring advocate views on this fast-moving issue. Stay tuned for more AVAC resources to help advocates navigate the ins and outs of the trial designs of the future.