In a study of 12 participants, researchers at Beth Israel Deaconess Medical Center (BIDMC) have demonstrated that a cocktail of three broadly neutralizing antibodies (bNAb) successfully suppressed virus in people living with HIV. A subset of participants also demonstrated long-term control of the virus months after antibody levels declined to low or undetectable. The findings are published in Nature Medicine.
"Our data suggest that the triple bNAb cocktail can lead to virologic control for a prolonged period of time in most people living with HIV following ART discontinuation," said co-corresponding author Dan H. Barouch, MD, PhD, director of the Center for Virology and Vaccine Research at BIDMC. "Larger studies are planned based on these results."
HIV remains a global public health challenge. In the United States, more than 1.2 million people are living with HIV, with nearly 35,000 new infections reported in 2021 alone. While ART-a combination of drugs typically taken daily -has transformed HIV from a fatal illness into a manageable long-term condition, it does not eliminate the virus. The antibody cocktail tested in this study could offer an alternative that reduces reliance on daily medication.
To evaluate the safety, tolerability and antiviral effect of the combination of three broadly neutralizing antibodies, Barouch and colleagues enrolled 12 volunteers living with HIV to receive three monthly infusions of the triple-antibody cocktail, with the option of receiving three more as long as participants remained virologically suppressed. Participants discontinued ART two days after their first antibody infusion.
Two participants' viral levels rebounded before the dosing period ended. Ten of the 12 participants (or 83 percent) maintained virologic suppression for the duration of the six-month bNAb dosing period. Of these, five showed viral rebound during the next six months, whereas five demonstrated long-term virologic control for the duration of the study.
"Overall, our study showed that three anti-HIV antibodies with significant breadth of neutralization were actually able to maintain virological suppression in the absence of ART at least during the dosing period in a majority of the participants," said co-corresponding author Boris Juelg, MD, PhD, a principal investigator at the Ragon Institute of MGH, MIT, and Harvard. "In a smaller subset, this control was maintained up to week 44 even when the antibodies had reached very low levels in the blood. Future studies are now needed to determine the exact mechanisms of control and how long it can last."
"Our data shows that broadly neutralizing antibodies may offer a new treatment strategy for HIV," said Barouch, who is also the William Bosworth Castle Professor of Medicine at Harvard Medical School. "Long-acting versions of all three of these antibodies are currently being developed, which will likely facilitate the development of a triple bNAb cocktail that may be administered once every six months for both HIV therapy and prevention."
Co-authors included Boris Julg, Victoria E. K. Walker-Sperling, Malika Aid, Kathryn E. Stephenson, Rebecca Zash, Jinyan Liu, Joseph P. Nkolola, Amelia Hoyt, Katherine Yanosick, Tessa Speidel, Erica N. Borducchi, Tetyana Murzda, Lori Maxfield, Michael S. Seaman, and Dan H. Barouch of BIDMC; Kshitij Wagh, Elena E. Giorgi and Bette Korber of Los Alamos National Laboratory; Mike Castro, Leonid Serebryannyy, Adrian B. McDermott, Lucio Gama and Richard A. Koup of the National Institutes of Health; Roberto Arduino of McGovern Medical School at The University of Texas Health Science Center at Houston; Charlotte-Paige Rolle and Edwin DeJesus of Orlando Immunology Center; and Wenjun Li of University of Massachusetts, Lowell.
This project was supported by the Ragon Institute of Mass General, MIT and Harvard. This project was also supported by National Institutes of Health (grants 298 AI124377, AI128751, AI145801, AI149670, AI164556, AI169615, AI177687, AI106408 299, TR001102 (Harvard Catalyst), and AI114381); and by the Bill and Melinda Gates Foundation Collaboration for AIDS Vaccine Discovery (grant OPP1146996). This research was also supported by the Intramural Research Program of the NIH, NIAID.
Boris Julg is a part-time employee of Leyden Labs, B.V. All other authors declare no competing interests.
About Beth Israel Deaconess Medical Center
Beth Israel Deaconess Medical Center is a leading academic medical center, where extraordinary care is supported by high-quality education and research. BIDMC is a teaching affiliate of Harvard Medical School, and consistently ranks as a national leader among independent hospitals in National Institutes of Health funding. BIDMC is the official hospital of the Boston Red Sox.
BIDMC is a part of Beth Israel Lahey Health, a healthcare system that brings together academic medical centers and teaching hospitals, community and specialty hospitals, more than 4,700 physicians and 39,000 employees in a shared mission to expand access to great care and advance the science and practice of medicine through groundbreaking research and education.
