Combined infusions of anti-HIV antibodies suppress the virus for an extended period of time

Combined infusions of anti-HIV antibodies suppress the virus for an extended period of time

According to a small study published today in the journal, people living with HIV who started on antiretroviral therapy (ART) in the early stages of infection experienced a long period of HIV suppression without ART after receiving two broadly neutralizing anti-HIV antibodies (bNAbs). Nature. The results suggest that bNAb combination therapy may offer a future alternative to daily ART for people living with HIV. The research was conducted by scientists at the National Institute of Allergy and Infectious Diseases (NIAID), which is part of the National Institutes of Health, in collaboration with researchers at the NIH Clinical Center; Maple Leaf Medical Clinic in Toronto; the Frederick National Cancer Research Laboratory; Harvard Medical School, Boston; and Rockefeller University, New York.

Although oral antiretrovirals are very effective in controlling HIV levels, it can be difficult for some people living with HIV to follow a daily medication regimen. In addition, medications can have long-term side effects due to lifelong use and create the potential for the development of drug-resistant viruses. In previous research, simple bNAbs have shown limited success in keeping virus levels low, in part because bNAb-resistant HIV already existed or appeared in the individual. To solve this problem, researchers at the NIAID Laboratory of Immunoregulation tested a double combination of bNAbs – called 3BNC117 and 10-1074 – targeting different parts of the surface of HIV.

The researchers conducted a two-tier clinical trial between September 2018 and January 2021. The first tier was a randomized, placebo-controlled Phase 1 trial involving 14 HIV-positive participants. These people had started ART during the early stages of their infection. They were removed from antiretrovirals shortly after receiving their first infusion of the bNAbs or placebo combination. 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 aim of the study was to see if treatment with bNAbs could suppress HIV in the absence of ART. None of the seven participants who received bNAb treatment had to restart ART until 28 weeks after the infusion, compared with six of the seven participants who received a placebo. The median duration of antiretroviral discontinuation was 39.6 weeks (bNAb group) and 9.4 weeks (placebo), respectively.

The second part of the study involved bNAb infusions in a group of 5 study participants who did not take antiretroviral therapy but still had low levels of HIV. In this small group, only two of the five participants in the study maintained complete suppression of the virus for an average of 41.7 weeks after bNAb transfusions.

The authors note that the bNAb combination was ineffective in suppressing HIV if participants harbored a virus resistant to one or both experimental antibodies before receiving the infusions. The presence of pre-existing antibody-resistant HIV poses a major challenge in the future, according to the authors. No safety issues occurred in the study and infusions were well tolerated.

The authors of the study conclude that bNAb combination therapy can be very effective in suppressing HIV in the absence of ART for long periods of time, provided that the antibody-resistant virus is not present at the time individuals begin antibody treatment. More studies are needed to confirm the results, but as new-generation bNAbs with increased power and durability become available, β€œthere is reason to believe that infrequent administration (i.e. “twice a year) of these antibodies, possibly with a long-acting injectable antiretroviral drug, could lead to HIV suppression without antiretroviral treatment for long periods (years) in infected people,” the authors wrote. .

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Materials provided by NIH / National Institute of Allergy and Infectious Diseases. Note: Content is subject to change in style and length.

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