Individuals with HIV who started receiving antiretroviral therapy (ART) in the early stages of infection achieved a long period of suppression of HIV without ART after receiving two broadly neutralizing antibodies to HIV (bNAbs), according to a small study published in the journal today. Nature. The findings suggest that bNAb combination therapy could offer a future alternative to daily ART for people living with HIV. The research was conducted by researchers from the National Institute for Allergies and Infectious Diseases (NIAID), which is part of the National Institutes of Health, in collaboration with researchers from the NIH Clinical Center; Maple Leaf Medical Clinic in Toronto; Frederick National Laboratory for Cancer Research; Harvard Medical School, Boston; and Rockefeller University, New York City.
Although oral antiretroviral drugs are highly effective in keeping HIV levels under control, it can be difficult for some people with HIV to follow a daily medication schedule. In addition, drugs can present long-term side effects from lifelong use and create the potential for drug-resistant virus development. In previous research, individual bNAbs have shown only limited success in maintaining low levels of the virus, in part because bNAb-resistant HIV already existed or appeared in the individual. To address this problem, researchers in the NIAID immunoregulation laboratory tested a double combination of bNAbs – called 3BNC117 and 10-1074 – targeting different parts of the HIV surface.
The researchers conducted a two-component clinical study between September 2018 and January 2021. The first component was a randomized, placebo-controlled phase 1 study involving 14 participants with HIV. These individuals started ART during the early stages of their infection. They were discontinued antiretroviral drugs shortly after the first infusion of bNAbs or placebo. Participants received up to eight infusions of bNAb or placebo – two in the first month and once a month thereafter – for 24 weeks. HIV levels and CD4 T-cell counts were measured every two weeks.
The purpose of the study was to determine whether bNAb treatment can suppress HIV in the absence of ART. None of the seven participants receiving bNAb treatment had to restart ART 28 weeks after the infusion, compared with six of the seven participants receiving placebo. The median duration of antiretroviral-free time was 39.6 weeks (bNAb group) and 9.4 weeks (placebo).
The second component of the study included bNAb infusions in a group of 5 study participants who did not use ART but still maintained low HIV levels. In this smaller group, only two of the five study participants maintained complete virus suppression for an average of 41.7 weeks after bNAb transfusions.
The authors note that the bNAb combination was ineffective in suppressing HIV if participants had a virus resistant to one or both experimental antibodies prior to infusion. According to the authors, the presence of pre-existing antibody-resistant HIV is a major challenge for the future. There were no safety concerns in the study and the infusions were well tolerated.
The study authors concluded that bNAb combination therapy may be highly effective in suppressing HIV in the absence of ART for an extended period of time, provided that no antibody-resistant virus is present at the time individuals begin treatment with antibodies. More extensive studies are needed to confirm the findings, but as new generation bNAbs with increased efficacy and durability are available, could lead to the suppression of HIV without ART for a longer period of time (years) in infected individuals, “the authors wrote.
National Institutes of Health
Sneller, MC, et al. (2022) Combined anti-HIV antibodies provide sustained virological suppression. Nature. doi.org/10.1038/s41586-022-04797-9.
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