Researchers led by a team from Mass General Brigham and the Ragon Institute have discovered why some people living with HIV who are given a treatment called broadly neutralizing anti-HIV antibodies (bNAbs) can safely stop taking standard, lifelong HIV medications and maintain control of the virus for years, while others given the same treatment do not achieve this remission. The findings, which are published in Nature , could potentially be used to design combination therapies that work for more people.
"Our results show that some people can go on to control the virus on their own without treatment because of a property of a type of killer T cell," said senior author David Collins, PhD, an investigator at the Ragon Institute of Mass General Brigham, MIT, and Harvard. "This is an important insight into how the body's natural defenses can be harnessed to achieve durable HIV remission."
For their study, Collins and colleagues analyzed blood samples from 12 people in four different clinical trials who received bNAbs and then stopped standard antiretroviral therapy. They compared samples from the seven participants who could control HIV after bNAb treatment for up to seven years (that is, keep the virus at very low levels) with samples from five participants who experienced viral rebound. They found that immune cells called CD8+ T cells of "post-intervention controllers" could multiply well and kill HIV cells efficiently. While bNAb treatment boosted these abilities, what mattered most was having these CD8+ T cell features before treatment.
"Control wasn't uniquely linked to the development of new types of responses; it was the quality of existing CD8+ T cell responses that appeared to make the difference," Collins explained. "Immunotherapies capable of enhancing virus-specific CD8+ T cells' capacity to respond to and fight infection, and capable of restoring the cells' ability to proliferate or renew themselves in all recipients, may dramatically enhance the likelihood of durable HIV remission elicited by bNAb administration."
Prospective studies with additional participants are needed to support the implication that HIV-specific CD8+ T cell features can predict responses to bNAb therapy and might also be targeted to allow more people living with HIV to benefit from this line of treatment.
"Efforts are underway to induce the same immune system properties we see in the post-intervention controllers in persons living with HIV," said Bruce Walker, MD, a co-author on the study and director of the Ragon Institute at Mass General Brigham. "Whether we will succeed remains to be seen, but I am cautiously optimistic."
Authorship: In addition to Collins, Mass General Brigham authors include Zahra Kiani, Jonathan M. Urbach, Hannah Wisner, Mpho J. Olatotse, Daniel Y. Chang, Joshua A. Acklin, Alicja Piechocka-Trocha, Nathalie Bonheur, Ashok Khatri, Mathias Lichterfeld, and Bruce D. Walker. Additional authors include Jesper D. Gunst and Ole S. Søgaard of Aarhus University, and Marina Caskey and Michel C. Nussenzweig of Rockefeller University.
Disclosures: None.
Funding: This work was supported by funding from United States National Institutes of Health (AI184606, AI155233, AI152979,AI176579, AI44462), Howard Hughes Medical Institute, and the Lundbeck Foundation (R381–2021–1405). Funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.
Paper cited: Kiani Z et al. "CD8+ T cell stemness precedes post-intervention control of HIV viremia" Nature DOI: 10.1038/s41586-025-09932-w
