Sunday, September 25, 2022

Combination anti-HIV antibody infusions suppress the virus for a long time

Individuals living with HIV who started taking antiretroviral therapy (ART) in the early stages of infection after receiving two broadly neutralizing anti-HIV antibodies (bNAbs) followed by HIV without ART, according to a small study published today in the journal HIV. achieved a long period of repression. Nature, The findings suggest that combination bNAb therapy may offer a future alternative to daily ART for people living with HIV. This research was conducted by scientists from the National Institute of Allergy and Infectious Diseases (NIAID), 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 The Rockefeller University, New York City.

Although oral antiretrovirals are highly effective at keeping HIV levels under control, it can be difficult for some people with HIV to adhere to daily medication. Additionally, the drugs may present long-term side effects from lifelong use and may lead to the development of drug-resistant viruses. In previous research, single bNAbs showed only limited success in keeping virus levels down partly because bNAb-resistant HIV was either already present or emerged in the individual. To address this problem, researchers from the NIAID Laboratory of Immunoregulation tested a dual combination of bNAbs — called 3BNC 117 and 10-1074 — targeting different parts of the surface of HIV.

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The researchers conducted a two-component clinical trial between September 2018 and January 2021. The first component was a phase 1 randomized, placebo-controlled trial involving 14 participants with HIV. These individuals started ART during the initial phase of their infection. They were weaned off antiretrovirals shortly after receiving their first infusion of combination bNAbs or placebo. Participants received eight bNAB or placebo infusions — two in the first month and once monthly thereafter — for 24 weeks. HIV levels and CD4 T-cell counts were measured every two weeks.

The aim of the study was to see whether treatment with BNAB could suppress HIV in the absence of ART. None of the seven participants who received BNAB treatment had to restart ART before 28 weeks post-infusion, compared with six of the seven participants who received placebo. The median duration of antiretroviral discontinuation was 39.6 weeks (BNAB group) and 9.4 weeks (placebo), respectively.

The second component of the study involved BNAB infusions into a group of 5 study participants who were not taking ART but still maintained low levels of HIV. In this small group, only two of the five study participants maintained complete suppression of the virus for an average of 41.7 weeks after BNAB transfusion.

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The authors note that the bNAb combination was ineffective in suppressing HIV if participants harbored a virus resistant to either or both experimental antibodies before acquiring infection. According to the authors, the presence of pre-existing antibody-resistant HIV poses a major challenge. No safety problems occurred in the study, and the infusion was well tolerated.

The study authors concluded that combination bNAb therapy may be highly effective in suppressing HIV in the absence of ART for extended periods, provided that antibody-resistant virus is not present at the time individuals initiate antibody treatment. Larger studies are needed to confirm the findings, but with the availability of next-generation bNAbs with increased potency and durability, “there is reason to believe that the rare administration of such antibodies (ie, two times a year). bar), possibly a longer-acting as well as injectable antiretroviral drug, may lead to ART-free HIV suppression for extended periods (years) in infected individuals,” the authors wrote.

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material provided by NIH/National Institute of Allergy and Infectious Diseases, Note: Content can be edited for style and length.

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