In a pioneering move addressing gender disparities in HIV research, Gilead Sciences has launched what is believed to be the first HIV cure trial in Africa, with a specific focus on women. The groundbreaking study, conducted in South Africa, aims to address the significant underrepresentation of women in HIV clinical trials despite their disproportionate disease burden, particularly in sub-Saharan Africa.
"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," explains Dr. Devi SenGupta, Executive Director of Clinical Development at Gilead Sciences and head of the company's HIV cure strategy.
The Gender Disparity in HIV Burden
The statistics paint a stark picture of gender inequality in HIV infection rates. Of the approximately 39 million people worldwide living with HIV, young women and girls bear a disproportionate burden. This disparity is most pronounced in sub-Saharan Africa, where women and girls account for 62% of new HIV infections. In KwaZulu-Natal, South Africa, where the trial is being conducted, women face a staggering 66% chance of living with HIV by their mid-30s—one of the highest incidence rates globally.
Despite these alarming figures, women have historically been underrepresented in clinical trials for HIV treatment, prevention, and cure efforts. This gap has limited understanding of how HIV therapies work across diverse populations and potentially delayed the development of effective interventions for women.
The FRESH Cohort: A Unique Research Opportunity
The trial recruited 20 young women from the Females Rising through Education Support and Health (FRESH) cohort, an observational cohort established over a decade ago by the Ragon Institute and the University of KwaZulu-Natal in Durban.
FRESH offers a multidisciplinary program combining scientific research with socioeconomic empowerment for young women at high risk of HIV infection. Participants receive twice-weekly classes, job training, and counseling addressing root causes of their elevated risk, including power imbalances in relationships and economic disparities.
What makes this cohort particularly valuable for cure research is their unique clinical profile. While participating in the program, the women undergo twice-weekly finger prick testing for HIV viral load. Those who test positive begin treatment immediately—within days of infection.
"Getting started on treatment early helps ensure that their viral reservoir is very small, because the treatment stops the virus in its tracks," Dr. SenGupta explains. "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."
This early intervention creates ideal conditions for testing immunotherapy-based HIV cure approaches, as participants have smaller viral reservoirs and relatively intact immune systems.
Overcoming Research Challenges in Resource-Limited Settings
Conducting a complex HIV cure trial in South Africa presented numerous logistical and cultural challenges. The research team had to navigate resource limitations, cultural contexts, and unexpected disruptions including the COVID-19 pandemic, floods, and political unrest.
"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," Dr. SenGupta recounts.
The success of the trial hinged on strong community relationships and trust built over years by the FRESH program. The research team conducted extensive community education before the trial to ensure participants and community members understood the study's purpose and procedures.
"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," Dr. SenGupta emphasizes.
Adapting Trial Protocols to Local Contexts
The research team had to adapt standard clinical trial protocols to accommodate local realities. For example, safety monitoring procedures that would typically release participants in the evening had to be modified for the South African context.
"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," Dr. SenGupta explains.
This flexibility and cultural sensitivity proved crucial to the trial's success. The participants demonstrated remarkable commitment, undergoing biopsies, multiple blood draws, overnight hospital stays, and tolerating flu-like symptoms throughout the study.
Implications for Future HIV Research
The trial represents a significant shift in HIV research priorities, emphasizing inclusion and diversity over speed. Dr. SenGupta notes that historically, "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."
The success of this trial could pave the way for more inclusive approaches to HIV research globally. By including populations that have traditionally been excluded from clinical trials, researchers can develop more effective treatments and potentially accelerate progress toward an HIV cure that works for diverse populations worldwide.
"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," Dr. SenGupta concludes.
Gilead's Broader HIV Research Initiatives
This HIV cure trial is part of Gilead's comprehensive approach to addressing HIV globally. The company is also making significant strides in HIV prevention research, particularly with its PURPOSE 1 trial studying lenacapavir for HIV prevention in adolescent girls and young women in Sub-Saharan Africa.
Dr. Moupali Das, Vice President of HIV Prevention Clinical Development at Gilead, highlights the company's innovative approach to including adolescents in clinical trials. "The revolutionary thing about the PURPOSE 1 trial is we sought to protect adolescents through research. Instead of excluding adolescents, we first evaluated safety in adults and then, after the first 300 adults had been studied, we convened our independent data monitoring committee to evaluate the early safety data."
This approach allowed for earlier inclusion of adolescents in the trial, potentially accelerating access to new prevention options for this vulnerable population. The PURPOSE 1 trial has shown promising results, with lenacapavir demonstrating similar pharmacokinetics in adolescents aged 16 and 17 years as in adults.
As Gilead continues to advance both treatment and prevention research, its focus on underrepresented populations—particularly women and adolescents in high-burden regions—represents an important shift in HIV research priorities that could ultimately help reduce global disparities in HIV outcomes.
