HIV research and development has a diversity problem. While this is not a new problem, it’s one that continues to draw attention—particularly during this pandemic year, when we’ve seen considerably low recruitment of people living with HIV in COVID-19 vaccine clinical trials and, subsequently, a renewed interest toward diminishing those gaps in forthcoming HIV research.
To assess the demographics of participants enrolled in trials for HIV drugs under development, researchers from the AIDS Treatment Activists Coalition (ATAC) conducted a systematic analysis of participant diversity in industry-sponsored studies for four companies actively involved in HIV research and development: Gilead Sciences, Janssen, Merck, and ViiV Healthcare. The analysis revealed that, among HIV trial participants, male participants were over-recruited by 34%; race-specific data was unreported for 65% of studies, and, when reported, was suboptimal; and geographic diversity was lacking, as a majority of study sites were in the United States, despite 75% of people with HIV living in Africa and Southeast Asia. ATAC Board member Michael Dorosh highlighted the analysis findings during a presentation titled, “Missing Data, Missing Diversity: Participant Demographics in Industry-Sponsored HIV Studies, 2010-2020,” as part of the 28th Conference on Retroviruses and Opportunistic Infections (CROI 2021) in early March.
In conversation with Terri Wilder, Liz Barr, Ph.D., M.S., a transdisciplinary researcher and longtime HIV activist, discussed the findings from ATAC’s diversity analysis, its broader implications, and the history of HIV research leaving the people most impacted behind. Barr has served as a community representative to the AIDS Clinical Trials Group (ACTG) and is a member of ATAC‘s Drug Development Subcommittee, a group that facilitates communication and sets agenda items between HIV/AIDS treatment activists and industry, including pharmaceutical companies.
A Diversity Report Card for Drug Companies
Terri Wilder: Thanks so much for speaking with me today. And congratulations on the presentation at CROI 2021. Before we begin talking about the presentation, can you tell me a little bit about ATAC and its history, mission, and key accomplishments, and the people involved?
Liz Barr: Sure. ATAC is the AIDS Treatment Activists Coalition. We are a national, U.S.-based coalition of AIDS activists, many of whom are living with HIV. We work together to end the epidemic by advancing research on HIV and AIDS. ATAC has a Drug Development Subcommittee that meets regularly with several pharmaceutical companies to provide an expert community opinion and input on drug development.
ATAC has been around for decades and has an active board of directors that includes Lynda Dee, Danielle Campbell, David Palm, and Andy Kaytes—a number of folks who have been involved since before I became involved in HIV activism, certainly.
Wilder: ATAC conducted a systematic analysis of industry-sponsored studies. What led ATAC to do this analysis?
Barr: In our relationships with pharmaceutical companies, part of what we do is give our perspective and input on drugs and their development. But then we also give our perspective and input on ways that companies can meet the needs of all communities affected with and living with HIV. ATAC had previously done a series of industry report cards that were very much like report cards—companies were graded on a number of different metrics. It had been an ongoing refrain in ATAC’s interactions with companies where we say, “You need to enroll more women. You need to enroll more people of color in the U.S. You need to enroll participants that reflect the geographic diversity of HIV.”
And the companies say, “OK, we hear you.” But then nothing seems to change. So, this systematic analysis was like a targeted reboot of the report card that was focused specifically on participant diversity, where we wanted to look at publicly available data and provide meat for the argument that we have been making, that participant diversity is suboptimal.
Wilder: The analysis focused on four pharmaceutical companies: Gilead, Janssen, Merck, and ViiV. Why these four pharma companies? It seems obvious because they develop HIV meds. But was there any reason why you didn’t expand it to other pharmaceutical companies?
Barr: We focused on these four companies because they are active in HIV R&D, and ATAC has relationships with these companies. And so, we have met with them and provided input. We know from our interactions with these companies that there is a stated willingness and desire to, quote, do better, on participant diversity. Also, we limited it to only these four companies to, one, make the project manageable, and two, because they’re very active in HIV R&D.
Sex and Race Data Are Underreported
Wilder: Tell me about the study’s background, methods—and, of course, the results.
Barr: Again, we limited the study to only industry-sponsored studies by these four companies that had a primary completion date between 2010 and 2020. We wanted to use publicly available data, so we searched clinicaltrials.gov for study information.
We wanted to document the extent of the problem so that we could have a really clear data-driven starting place for future conversations with industry, and also with other advocacy groups and organizations that ATAC might interact with. We had a number of inclusion and exclusion criteria for the studies. Were they funded by one of these four companies? Had they opened for enrollment yet? Had they finished recruiting? And so, all of those processes.
We reviewed the clinical trials registry listings and collected participant demographics when those data had been entered into clinicaltrials.gov. If they were not researched through the websites of CROI and other large conferences, we did our due diligence here to try to locate age—the median and mean age of participants—sex, gender, race, and ethnicity, when they were reported. We looked at the inclusion and exclusion criteria for the studies that were reported. We really just tried to get as much data as we could.
Then, we looked at the data across time and across companies. We did not include phase 1 studies because those do not need to be reported to clinicaltrials.gov. There wasn’t data for all four companies on their phase 1 studies, and since we didn’t know what we didn’t know, we didn’t include phase 1 studies.
The major findings were that data is unreported on sex, race, and ethnicity, and when data are reported, when those variables are reported, they do not reflect the demographics of HIV. We found that participant sex was reported for most studies, but one of the studies that did not report participant sex was an observational PrEP study, enrolling almost 65,000 people, that had not reported results. We could not find the results reported anywhere. That means that of a total of 133,000 study participants that were included in these studies, we were able to find the sex for just about 66,000 of them—so, just about less than half. We don’t know the sex of half of the participants in these studies.
Race was reported significantly less often. It was reported for a total of 40,000 participants, which left 86,000 participants for whom race was not reported. On all of the metrics that we looked at—age, sex, race and ethnicity, and location—we found that the companies were not enrolling participants that look like people living with HIV.
Wilder: This sounds like a huge undertaking. How long did it take ATAC to do the analysis?
Barr: It was a several-month-long project, and it went through several rounds of analysis and review and conversation for most of the board members. We were happy to be able to submit it to CROI and that it was accepted there.
A Long History of Being Left Out of HIV Trials
Wilder: There’s a very long history, dating back to the early years of the AIDS epidemic, of people being left out of HIV-related clinical trials—most notably, women. Why do you think this is still happening? Why didn’t we learn from the early years of the epidemic that you have to include people in data collection and make sure it’s representative of the community of people living with HIV?
Barr: That’s a great question that I wish I could give you a sound-bite answer to. I think, in a lot of ways, we did learn—although it depends on who we is. Advocates and activists working around HIV have learned some strategies and tactics for engaging with industry, government, and other entities that are doing the research, to ensure that our voices are heard.
One of the things that has not changed is that there is a real need to enroll studies quickly, and that can make companies turn to the same tricks that worked for them in the past—or turn to the same community partners, or the same recruitment strategies that have worked in the past. But we’ve also seen efforts by some of these four companies included in the analysis to do better. There have been individual studies that have, for example, set specific recruitment targets set out by the company. And then, the sites have met those targets.
So, ATAC has seen that when the company says, “You’re going to enroll 40% women. You’re going to enroll 60% people of color”—whatever the target, the metric that the company sets—the sites will meet it, if it’s set by the company. Activists and advocates can give our perspective as to what the target can be, and then the companies would need to respond by setting that target.
Wilder: If the company doesn’t set a target as part of the research plan, then it doesn’t tend to happen?
Barr: So, it’s about having voices of affected communities represented early in development. And the government networks have done a really great job of bringing in community perspectives early in development. So that’s part of it.
But, if it is not a requirement, it is unlikely to happen.
Wilder: I found the analysis really interesting, but in some ways not surprising that there was male over-recruitment. And there seems to be a lack of geographic diversity. Why is it important to have the geographic data?
Barr: We were not surprised at how U.S.-centric these studies were. But I was discouraged by the extent of it. It’s important to have geographic diversity within the U.S. because, certainly as there’s all this energy around Ending the HIV Epidemic and EHE jurisdictions, that’s going to be an opportunity to leverage that momentum to reach those communities.
But also, globally, it’s really important that the most geographically impacted regions have to be engaged early in drug development—for one, a matter of ethics, and, two, a matter of practicality. Implementation issues are going to be very different moving from geographic region to geographic region, and it’s important to identify those early in development.
And then, from an ethical perspective, we’re seeing COVID vaccine geographic disparities, in terms of access to vaccines. So, it happens over and over again that we need to include the most impacted communities early and meaningfully.
Wilder: I’m wondering in particular about the lack of trans-inclusive research questions. If you’ve looked at, say, the time period between 2020 to 2030, might that change?
Barr: Absolutely. This 10-year period does present a picture of limited transgender inclusion. But there are currently enrolling studies that we couldn’t include, because they’re currently enrolling. There’s Janssen’s vaccine study and Merck’s upcoming IMPOWER 24 PrEP study, for example. These will capture important data related to transgender participants.
And then, transgender participants might have been more represented than the data indicate. Companies do need to report to clinicaltrials.gov participant sex. It is also optional to report gender, so there sometimes might be discrepancies between how the data is collected and reported. We are hopeful that if we repeat this analysis in even five years that we might see companies taking advantage of relationships they have with other entities, like academic partners and federal research networks, who are doing trans-inclusive research, often with industry support.
So it’s not that these companies are not doing anything. They might be funding or supporting projects that are led by investigators, or lending support to government-sponsored studies. But ATAC does think they would be well served to develop and promote their own trans-inclusive research agendas.
Wilder: When you say that it may depend on the way the data was collected, are you saying that, for example, a transgender woman might have been documented as male assigned at birth?
Barr: Correct. Sex is reported, and it is required to be reported. Gender is an optional reporting. Sometimes people ask about sex, or they report sex but are really talking about gender. Sometimes they are reporting sex assigned at birth and not also collecting and disaggregating by gender.
We saw it in the sex/gender relationship, and also in the sex and race relationship, that data is not disaggregated. We can tell you how many women were involved, but we can’t tell you how many of those women were Black, or white, or Native American. Clinicaltrials.gov gives one standardized option for submission of sex, which is male/female, and then there’s this optional, customizable gender field.
I know I’m shifting subjects here, but there are three race and ethnicity categories in clinicaltrials.gov, and you can select which are most appropriate, if they were collected. There’s significant variability in how race and ethnicity are reported. It is a little more challenging to make comparisons in terms of race and ethnicity. But it’s nearly impossible to disaggregate on any of these variables—age, race, ethnicity, sex, gender.
Can Improving Data Transparency Build Trust?
Wilder: Your conclusion statement, or one of your conclusion statements, stated: “Improved data sharing and data transparency could be key drivers of increased trust in ‘Big Pharma’ and may play a role in shifting community engagement.”
That was a really interesting statement because I think Pharma is constantly worried about their reputation and perception by community members. Can you say more about how data sharing and transparency could increase trust and shift community engagement?
Barr: ATAC would be thrilled if one outcome of this report was that companies would provide publicly the missing data. We would love to have that data that has not been reported be publicly available. I think that trust would be increased if, in another few years, we were able to repeat this analysis and say, “OK. Here’s where we were in 2020. Now it’s 2025 and the companies have changed in these ways.”
I’ve been involved in HIV activism since 2009. And it started way before me, these conversations about needing more representations of the diversity of people affected by HIV in HIV studies. This is, as you said, not a new conversation to be having. Now we have a very complete picture of this limited snapshot in time.
We, the activist community, ATAC, would love to hear some actionable steps that the companies might take. We’ve provided them in the report with a number of ideas so that we could then look and say, “OK. We tried these things, and now, three years later, by putting in enrollment targets, we have changed the enrollment of our participants.”
Wilder: You have a great graphic in the slide pertaining to cross-industry recommendations. There were six: enroll more women, enroll participants that reflect the diversity of people living with HIV, disaggregate transgender women, replace upper age limits with specific health-related exclusion criteria, prioritize enrollment of participants from countries most impacted, and increase transparency of phase 1 portfolios.
This graphic also shows that race-specific data is underreported by 65%, and that the majority of studies are U.S.-based, while 75% of people living with HIV live in Africa and Southeast Asia. While I realize that this was looking at industry studies, I’m wondering if this can inform scientific research across the board?
Barr: Yes, absolutely. You’ll have to stay tuned for what projects might be coming next from ATAC, in terms of analyses. But I know that our recommendations are very similar to calls that have been made by advocates working with the government networks, with the Delaney Collaboratories—even also our partners in the funding world.
Mike McCune [M.D., Ph.D., an HIV researcher] had a great paper a year or two ago about the need to engage African countries in peer research earlier. So it’s not only advocates making these recommendations. Our friends at NATAP (National AIDS Treatment Advocacy Project) have done a lot of advocacy around age, as, especially in the U.S., the population of people living with HIV is older. So, while they aren’t formed by the specific analysis, we do see these recommendations as part of a broader HIV advocacy agenda.
Wilder: I think this can also inform scientific research at the individual and team level. The principal investigator on a research grant or the research team should be thinking about what their role in recruitment is—regardless of if it’s written into their grant or not.
Barr: It really is, I think, a broad culture change that might be happening slowly, in terms of the scientific research community. The upper age limit, for example, that’s a place where we have seen some change happening at individual study levels. So you can have an upper age limit of 55, or you can have an upper age limit that’s actually based on a specific health-related criteria. Is it that being 56 is the problem? Or is it that heart disease is the problem?
There’s a huge wealth of community-based expertise on issues of aging. There’s a large body of literature showing excessive morbidity among older women living with HIV, especially women of color. And so every one of these areas touches the other. We are eager to talk with our partners and collaborators about how these recommendations could be put into action.
Wilder: Any concluding thoughts that you think would be important to share?
Barr: We’re really excited to have the report live on the ATAC website. We’re excited to have some data that can inform future conversations and interactions with the research community and the advocacy community. We hope that this is just one part of the conversation, not the end of it.
Liz Barr spoke with TheBodyPro as a member of ATAC and not as an employee of the National Institutes of Health.