Gilead Prioritizes Women With Its First HIV Cure Trial In Africa
A conversation with Devi SenGupta, MD, MPhil, head of HIV cure strategy, global development lead for HIV treatment and cure, Gilead Sciences
Of the approximately 39 million people worldwide living with HIV, young women and girls bear a disproportionate burden. This disparity is starkest in sub-Saharan Africa, where women and girls account for 62% of new HIV infections. Within this region, Eastern and Southern Africa exhibit particularly pronounced gender disparities in new HIV diagnoses. Despite this, women are significantly underrepresented in clinical trials for HIV treatment, prevention, and cure, hindering our understanding of how HIV therapies work across diverse populations.
For the past several years, Gilead Sciences has been working against this hurdle and toward a cure by enrolling the first known HIV cure trial in South Africa.
In this Q&A, Gilead’s head Of HIV cure program strategy, Devi SenGupta, discusses the challenges and triumphs of a groundbreaking HIV cure trial in South Africa, exploring logistical hurdles, the importance of community trust, and the impact of cultural context on clinical research.
Generally, female enrollment is lower than that of men in clinical trials. How is that apparent here, specific to HIV therapies?
Women are underrepresented in clinical studies across most therapeutic areas. In general in virology, and then drilling down into trials for HIV treatment and cure, they're very underrepresented. The trial we ran was the first HIV cure trial to be done in Africa, to our knowledge.
Enrollment of women is getting better because of increasing awareness and regulatory authorities’ diversity goals. For example, in our HIV treatment trials, the FDA is requiring certain minimum percentages for enrollment of women and other demographics. It's changing, but there needs to be more change.
What are some factors that cause low enrollment rates for girls and young women in HIV treatment and cure trials?
It’s mostly a logistical issue. Historically, trials are done where they're most feasible to get results and approvals faster to get the medications to the people who need them. Often, speed has outweighed or been a bigger priority than inclusion. But if you slow down, are more selective of the sites, and are intentional about increasing diverse enrollment, your results will be more generalizable and maybe more successful in the long run.
How do providers and patients feel about clinical trials for HIV treatment and cures?
Providers would like to enroll as diverse a participant population as possible, but it may be harder to recruit women. Clinical trials are very demanding of participants, and HIV cure clinical trials can be extremely complex, sometimes requiring participants to come to the clinical trial site several times a week. They may require overnight hospital stays for safety monitoring and lots of blood draws. They're a big time commitment and in many cases, women carry a lot of different work and household responsibilities, so it's hard for them to commit to going to the hospital or the clinic a lot for multiple visits or complicated procedures.
If the enrollment of this participant group remains as-is, what’s at risk?
We may miss the opportunity to understand how our drugs work in different types of populations with different genetic backgrounds, different genders and different lived experiences or daily realities; the results may not be generalizable to all the people who have a need for the new drug. If you do a trial in only cisgender white men, there are some things you may not be able to discern in terms of efficacy or safety in other populations. You may have to go back later to do trials in other populations, and then you and the people who are waiting for the drug lose time.
You also miss the opportunity to understand diverse perspectives on how you design the trials — how to retain people and make sure they're comfortable with how you're running the trial. Especially in HIV cure trials, it's going to be a very iterative process, because it's going to take a long time to get to a 100% efficacious, globally scalable lifelong cure for HIV. So, if you're not using that opportunity to learn along the way and make your trials and interventions better, you're missing out.
Twenty women from the Females Rising through Education Support and Health, or FRESH, cohort enrolled in this trial. Who are they, and how were they recruited?
This interventional trial recruited young women who are part of an observational cohort established by the Ragon Institute and the University of KwaZulu-Natal more than 10 years ago in Durban, KwaZulu-Natal, South Africa. It's a multidisciplinary program that brings together scientific learning and socioeconomic empowerment in a place where young women are at extremely high risk of acquiring HIV. In KwaZulu-Natal, by their mid-30, women have a 66% chance of living with HIV. It's one of the highest, if not the highest, incidences in the world for HIV, especially in young women.
The FRESH (Females Rising through Education, Support and Health) program offers young women an opportunity to enhance life skills in addition to standard HIV prevention options. They're offered twice-weekly classes and job training, as well as counseling to try to get to the root causes of why the incidence and the risk are so high in this group. It has to do with power imbalances in relationships between young women and older men, the economic disparities between the two genders, and the women’s relative lack of autonomy due to societal forces. The FRESH program trains these young women with life skills that allow them to be independent.
While they're part of that program, they’re also getting finger prick testing for HIV viral load twice a week. And as soon as that test turns positive, they're started on HIV treatment. This means we have a cohort of young women who have started treatment at the very earliest stages of infection —within days of being infected and diagnosed.
Getting started on treatment early helps ensure that their viral reservoir is very small, because the treatment stops the virus in its tracks. That reservoir is smaller and less diverse. It doesn't have as many different variants of the virus. Because you're catching the infection early, their immune system also hasn’t been severely damaged. Being treated for a hyperacute infection makes them potentially good candidates for an immunotherapy-based HIV cure.
We could not have done a complex interventional trial in this cohort without the investigators and clinic staff who had very close relationships and established trust with the local community and those FRESH participants. These women have been coming to the clinic for years; they're like a family. The investigators and the site staff also did a lot of community training ahead of the trial so that everybody understood what the trial was and what it wasn't. There are a lot of nuances that require culturally competent explanations and education of the potential participants and the broader community.
How, then, is HIV infection perceived in South Africa?
Based on discussions that I've had with people who are part of the community in South Africa as well as our own global HIV Cure Community Advisory Board, it is much more part of the overall consciousness there because it's so prevalent. There is still quite a bit of stigma attached to it. Thinking back to conversations I had with some of the young women in the observational cohort, there's tremendous hope and desire for future generations not to have to deal with the burden of high prevalence of HIV in their community and to have the independence and the education to overcome the circumstances that lead to the high prevalence.
Let’s talk about the complexity of this trial in a resource-limited setting. What should we understand about the clinical care and research landscape in this part of Africa?
When we first considered running this trial with the cohort, there was a lot of discussion to figure out whether this site had the specific capabilities and processes in place, and how we could be creative about setting them up for success. Providing care, running the FRESH program, and doing a lot of great science, that was all well established. But doing an industry-sponsored trial was something new both for the site and for Gilead to run an early-stage clinical trial in a setting we hadn't before. Most HIV cure trials are done in the U.S. and Europe, and they're generally small, complicated trials. We felt scientifically it made sense, but we also wanted to make sure we did it with the right partners. Because of the characteristics of the people who run the FRESH program, we decided they were the right partners: scientifically capable, mission-driven, they shared common scientific and ethical values with us, and, most importantly, they had incredible resilience.
One of the misconceptions was that participants wouldn’t understand what they were getting into. Will we be able to get a truly informed consent from them? Will they be anxious about the potential side effects? All those are valid questions. But the FRESH cohort participants were some of the bravest people I've ever met in my life. Because they had this established relationship and trust with the site, there was no issue in making sure that they knew exactly what to expect from the study. They stayed the course through the whole trial; they underwent biopsies, multiple blood draws, overnight hospital stays, and tolerated flu-like symptoms. They were able to power through all of those things.
There were a lot of disruptions that could have derailed the trial, yet everybody remained fully committed. We ran into the COVID-19 pandemic, some floods, and political unrest. Even the brand-new clinic was almost completely destroyed, and the clinic staff had to go on foot to check on trial participants in their homes. We wondered many times whether this trial would happen, whether we were going to have to stop. Not because of anything intrinsic to the participants or the site staff or the trial itself, but because of these events that were outside of everybody's control. It's a small trial, but it was a big effort and I hope that it will pave the way for more innovation in how the field approaches challenging questions.
You mentioned not running the trial in a traditional way. What did you do differently?
For some of these interventions, we have a certain minimum period of safety monitoring. It might be that a person comes into the clinic, gets dosed in the morning, and then they're observed for 8 hours before they can go home. However, the sites told us that they could not send these young women home at 7, 8, or 9 p.m. after the 8-hour observation period because it wouldn't be safe. We needed to be flexible and arrange for an overnight stay. We wouldn't have thought of that because we don't know the local context. Internally, it was a matter of educating the team and bringing them on board.
Are there any other lessons learned that can apply to an upcoming trial or be helpful to other sponsors?
If there's an important scientific and clinical question to be asked, I hope this encourages people to be creative about how to ask those questions and how to embrace multisector partners and participants that normally wouldn't be included. The success of this trial really was because of the unique commitment and capabilities of all the different parties involved. I hope this encourages people to collaborate in ways that may not be the most obvious or the fastest on the surface but ultimately will teach more than if we stick with routine approaches.
About The Expert:
Devi SenGupta, MD, MPhil, is executive director of clinical development at Gilead Sciences, leading the company’s HIV cure strategy and a long-acting treatment development program. Before joining Gilead in 2015, she was a physician scientist leading translational HIV immunology research at the University of California San Francisco (UCSF). As head of Gilead’s HIV cure program, Dr. SenGupta provides strategic direction for cross-functional internal teams and external multi-stakeholder collaborations developing combination approaches aimed at achieving long-term HIV remission. She also serves on the steering committee for the International AIDS Society (IAS) HIV Cure Industry Collaborative Group and was appointed to the Advisory Council of the California HIV/AIDS Research Program (CHRP). Devi is now also serving as the Global Chair for the Women at Gilead Employee Resource Group.