In a significant advancement for HIV treatment research, scientists in South Africa have conducted the continent's first clinical trial aimed at achieving long-term HIV remission without the need for lifelong antiretroviral therapy (ART). The groundbreaking Phase IIa study, conducted in KwaZulu-Natal, offers new hope for people living with HIV in a region where the disease burden remains exceptionally high.
The trial, led by Professor Thumbi Ndung'u of the Africa Health Research Institute and the University of KwaZulu-Natal (UKZN), tested a novel therapeutic approach combining two broadly neutralizing antibodies (bNAbs) with an immune stimulant in 20 South African women living with HIV.
Novel Therapeutic Approach Shows Promising Results
The study utilized a combination of vesatolimod (VES), a toll-like receptor 7 (TLR7) agonist, alongside intravenous infusions of two potent broadly neutralizing antibodies: VRC07-523LS and CAP256V2LS. This regimen was designed to rouse dormant HIV from its cellular reservoirs while simultaneously boosting the immune system's ability to target the virus.
"This is a pivotal moment for HIV science in Africa," said Professor Ndung'u. "It's the first HIV remission trial conducted on African soil. It took years of consultation, partnership, and perseverance to make it happen."
All participants had been on suppressive ART for at least 12 months before entering the trial. Following the experimental treatment, they underwent analytical treatment interruption (ATI) beginning on day 35, allowing researchers to assess viral rebound patterns and the duration of potential remission.
The results showed varying degrees of success. While seven participants needed to restart ART within 16 weeks due to viral rebound, four others managed to remain off treatment for up to a year. Most remarkably, one participant has continued to control the virus without ART for 2.5 years, suggesting the possibility of long-term immune-mediated control.
"We cannot say that this is a definitive cure, but it is a significant step toward understanding how we can achieve remission for people living with HIV," Ndung'u explained.
Addressing a Critical Need in High-Prevalence Regions
The significance of this research is amplified by the local context. In parts of KwaZulu-Natal, including the Umkhanyakude District, HIV prevalence reaches nearly 60% among women aged 25-44, underscoring the urgent need for innovative treatment approaches.
"Wouldn't it be a great idea if people could take medication for maybe two years, maybe five years, and then get off the ART completely?" posed Ndung'u, highlighting the potential life-changing impact of achieving sustained HIV remission.
The study distinguishes between two approaches to addressing HIV: complete eradication and functional remission. While eradication—removing all traces of HIV from the body—has been achieved in only seven to nine cases globally through complex procedures like bone marrow transplants, remission offers a more accessible goal where individuals can control the virus without daily medication.
Women-Focused Research Addresses Historical Gaps
Professor Kirsta Dong, Clinical Director of the FRESH Cohort and Professor of Medicine, emphasized the importance of ensuring women, particularly those in sub-Saharan Africa, are adequately represented in HIV cure research.
"We can't simply assume that what works in other parts of the world will work here," Dong noted, pointing to the unique challenges faced by African women living with HIV.
Dong and Ndung'u have collaborated since 2013, when they established a cohort of young women in Umlazi, South Africa, with the goal of detecting HIV during the hyperacute phase—just before the virus fully establishes itself in the body.
"We thought, can we catch HIV so early that we could change the course of the infection entirely?" Dong recalled.
Their research has already demonstrated that early treatment can significantly reduce the establishment of long-term viral reservoirs, a key factor in achieving remission.
Safety Profile and Future Directions
The safety profile of the experimental regimen was generally favorable. No serious treatment-related adverse events were reported among the 20 participants. One participant discontinued vesatolimod due to mild cytokine release syndrome, while 18 experienced infusion-related reactions that resolved within two days.
Five participants completed the 43-week analytical treatment interruption without requiring ART restart, with two maintaining viral suppression below 50 copies/mL—the threshold typically used to define undetectable viral load.
The research team faced numerous challenges, including political unrest, flooding, and the COVID-19 pandemic, which temporarily shut down their clinics. "We lost everything—every stethoscope, every desk, every tool," Dong recalled. Yet, the team persevered, relocating to continue providing treatment without interruption.
A Model for Complex Research in Resource-Limited Settings
This trial demonstrates that complex HIV cure research can be successfully conducted in resource-limited settings, providing a model for future studies. The researchers emphasize that strong community involvement and collaboration between scientists, participants, and stakeholders were essential to the project's success.
"This kind of complex research can be done, but it requires collaboration between researchers, the community, and stakeholders. Without cooperation, it would be impossible to move forward," Ndung'u stated.
As these studies continue, the researchers hope that by 2030, their work will contribute to a new era of HIV treatment where lifelong ART may no longer be necessary for everyone, and the possibility of remission could become a reality for many living with HIV in sub-Saharan Africa and beyond.
"This is not just about curing HIV for one person," Dong emphasized. "It's about making a global impact, helping people across the world, and ensuring that the next generation of scientists, particularly from Africa, will lead the way."
