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.”
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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.
Monthly infusions
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.
Virological suppression
“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.”
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