How Gilead Includes Patients Most Affected By HIV In Its PrEP Trials
A conversation with Moupali Das, MD, MPH, vice president, clinical development, HIV prevention and virology pediatrics, and head, HIV prevention, Gilead Sciences
When thinking about diverse participant enrollment in a clinical trial, it’s easy to focus on race and ethnicity. And while it’s an important demographic criterion to consider, there are many more — and many intersecting — criteria to consider.
Gilead Sciences knows well the significance of getting into the nitty-gritty of diversity, the subpopulations that might be small but are wildly important to scientific research. For example, in HIV prevention, it is critically important to include participants from populations that are disproportionately affected by HIV incidence. Such is the case with their PURPOSE 5 trial, a follow-on to their PURPOSE 1 HIV prevention as pre-exposure prophylaxis (PrEP) trial for cisgender women, which included adolescents and pregnant women, and PURPOSE 2, which studied PrEP across the world in cisgender gay men, other men who have sex with men, transgender men, transgender women, and gender non-binary individuals.
In PURPOSE 5, Gilead is evaluating the potential benefit of twice-yearly subcutaneous lenacapavir for PrEP among people in the U.K. and France not currently benefiting from daily oral PrEP. As of last reporting, they’ve enrolled 90% of their target number of participants, and about 50% of those participants are members of high-priority populations, e.g., populations disproportionately affected by HIV incidence.
In this Q&A, Gilead’s VP of Clinical Development, HIV, Moupali Das, shares how the sponsor approaches diverse participant recruitment and enrollment, highlighting the importance of early demographic research in one study and careful, intentional PI selection in another.
How did your diverse enrollment efforts materialize in PURPOSE 2, and how did that inform your approach to enrolling PURPOSE 5?
Moupali Das, MD, MPH: There's an intersectional disproportionate highly likelihood of HIV acquisition among vulnerable groups — cisgender gay men, other men who have sex with men, trans folks, trans men, trans women, and gender non-binary individuals — crossed with race and/or ethnicity. To identify those groups in the U.S. for PURPOSE 2, we first looked at the epidemiology of HIV using CDC statistics of new diagnoses of HIV. You can follow trends, but not every health department across the country collects nuanced information about different gender minorities. So, we consulted the National HIV Behavioral Surveillance (NHBS). The CDC studies a different disproportionately affected group every year, with men who have sex with men, heterosexuals, and transgender people. We reviewed city-specific NHBS transgender data to understand HIV incidence in transgender people in different cities. In summary, in the U.S., we picked clinical trial sites in the locations where the HIV incidence was highest among the different key populations, because we wanted to study prevention in the people who would need it most.
We had a giant spreadsheet called the site-specific recruitment plan. And each site had different goal numbers based on the demographics and the HIV epidemiology in their city or location. If the city had more people of African-American or Black descent and HIV diagnoses were high in that population, we requested higher goals for recruitment and enrollment for this population group. If another city had higher proportions of people of Latina background with high rates of diagnoses, we would request that those sites have higher recruitment goals for that population. In the U.S., we tailored site-specific recruitment goals by geography, demographics, and HIV incidence. By following these strategies, in PURPOSE 2 we successfully recruited a highly diverse participant population: 67% identified as people of color, 63% as Hispanic/Latina, and 22% represented gender diversity.
For PURPOSE 5 in France and the U.K., where oral PrEP is readily available, we wanted to understand the additional benefit of consistent, persistent protection with a long-acting twice-yearly injectable. We specifically studied people who were not currently receiving oral PrEP but met criteria for PrEP eligibility according to their national guidelines to demonstrate the relative benefit of a long-acting regimen compared with oral PrEP in terms of PrEP persistence or adherence and continuation over a one-year period.
We were very intentional in having a different approach for PURPOSE 5. We know, based on public health statistics, that cisgender gay male populations in the U.K. who have had strong uptake of oral PrEP have had declining rates of HIV infection but that HIV case rates have been increasing in other vulnerable and marginalized groups, including heterosexuals, sex workers, and substance users. In France, the rate of HIV diagnoses among men who have sex with men has remained stable, but certain groups, such as young gay men and migrant populations, have had increased rates.
However, because there are differences in the way the HIV statistics are collected, and because there are also tremendous differences even among sites in a city where groups are most disproportionately affected by HIV, we did not require each site to have a site-specific recruitment plan like in PURPOSE 2. Instead, each site needed to recruit at least half of the people who were, for their location, disproportionately getting HIV and not on PrEP. We also wanted to give more flexibility to the investigators, the sites, and the community groups, because they know their epidemic and their people who were at high likelihood for HIV acquisition and not on PrEP. Some sites did gender-affirming care, so we knew they could have a higher likelihood of recruiting trans folks. Then, a particular site in France may have expertise with a gay male clientele, but we would ask them to consider expanding into maybe migrant gay men or young gay men, both of whom are disproportionately affected by HIV.
It sounds like the PI and site selection for PURPOSE 5, then, is very intentional, even critical, to finding the right patient populations. How did you find them?
I receive a lot of inquiries from companies proposing AI for site recruitment by combing through various Big Data sources. This approach does not necessarily work for our proposed participant populations, particularly for a disease that continues to have this level of stigma.
Figuring out which sites to work with is really critical. When we were choosing sites for PURPOSE 1 and PURPOSE 2, we sent feasibility surveys with nuanced questions about their populations in a lot more detail than you would for a new HIV treatment trial, and then we did Zoom calls with every site and spoke to the investigators and their site staff. Once we were able to travel after shelter-in-place restrictions were lifted, we added site visits.
For PURPOSE 5, in France and the U.K., we did feasibility surveys, Zoom calls, and I visited several sites in London and Paris. I also had the opportunity to visit a community association that provides services for sex workers with an investigator who is an infectious disease physician and clinical trialist, and he shared that he recruited participants to enroll in HIV prevention services, including PrEP, at a bathhouse. He also shared that he was able to rapidly establish rapport with clients as he is fluent in French, as well as Spanish and Portuguese, since there is a lot of migration of sex workers from Spanish- and Portuguese-speaking countries.
And you have to balance enrolling harder-to-reach vulnerable populations, which can take longer to enroll, and completing the study and efficiently getting to an answer. Sometimes it is worth it to go slow to go fast in drug development because having the most appropriate participants will allow us to get better results.
You mentioned the PI being involved in the community outside of his practice. Is patient recruitment their responsibility, or do you facilitate that?
Yes, participant recruitment is the responsibility of the site. We specifically look for people who know how to find folks and work with the demographics of interest. We helped facilitate it by support for recruitment and retention. There are different ethics regulations in France and the U.K. governing recruitment. So, of course, we follow all the local rules and regulations. In the U.S., for PURPOSE 2, we had supported study level participant recruitment on Grindr and other sites like Jack’d and Scruff. We always do a mixture of active and passive recruitment. Sometimes, just saying Gilead is doing a new study and offering information at a clinic is enough. Other times, when we are looking for participants not currently receiving PrEP care, we have to innovate our social and digital strategies for outreach.
But for PURPOSE 5, we wanted fewer people, approximately 250 people, not 3,000, so our sites did not want a broad study-wide advertising campaign as it would likely result in too much interest. So, the site preferred to use word of mouth and their own connections in the community. Every site we picked had robust community engagement, whether from staff or with community associations.
Now, the majority of participants enrolled in this trial have some level of higher education. What impact might that have on PrEP persistence?
We think that education can be correlated with adherence, but there are also other factors associated with adherence. You could have a well-educated young person who may have poor adherence, as it is well documented that adherence increases with age across a variety of medical conditions. So, in this case, the association of youth with adherence might be stronger than education. I wouldn't say that all educated people are good at adherence. Just look at some doctors who are terrible at taking their medication. Yes, we're highly educated, but sometimes I cannot even remember to take my vitamins!
Education also correlates with socioeconomic status, which may also be important because empowered, well-educated gay men in the community who've been part of HIV prevention clinical trials and this work and volunteering for years are really good at taking oral pills. In PURPOSE 5, we were trying to get into other communities, which may include educated people, but we’re really focusing on people who are on the margins of society.
Just to note that the level of education in the PURPOSE 5 study (82%) was similar to the DISCOVER study (87%), our study of two oral PrEP products.
What lessons learned or best practices developed in PURPOSE 5 do you plan to continue in future HIV PrEP research?
Our learnings from PURPOSE 5 resonate with our experiences in the earlier trials and historically at Gilead. It is critically important to be clear about our expectations from the sponsor/study team perspective, repeatedly engage and communicate as we review study recruitment and retention by regularly engaging with investigators/site staff, and to course correct as needed to ensure that we are curating the optimal participant population to best answer the trial questions and achieve the objectives. In this case of HIV prevention trials, and I believe this is generalizable to other therapeutic areas, it is important to know the local context and epidemiology of the disease you are seeking to prevent, treat, or cure to ensure that each site in each location is recruiting the most disproportionately affected individuals who may have been historically excluded or underrepresented in clinical trials. This approach will optimize the generalizability of the results and help address any potential disparities or inequities in outcomes.
About The Expert:
Moupali Das, MD, MPH, is vice president, clinical development, HIV prevention and virology pediatrics, at Gilead Sciences. She is an infectious diseases/HIV trained physician with a background in academic medicine and public health. As head of HIV prevention, she leads high-performing cross-functional teams accountable for the overall development strategy and the conception, design, and execution of HIV prevention clinical trials from Phase 1 through Phase 4. She is dedicated to ensuring efficient development and regulatory approvals to support rapid access to innovative products to help end the HIV epidemic. She oversees the pediatrics team, who are deeply committed to ensuring the development of pediatric formulations for Gilead’s virology medications.