According to a small study published today in the journal, people living with HIV who started antiretroviral therapy (ART) in the early stages of infection achieved a long period of HIV suppression without ART following receiving two broadly neutralizing 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 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; the Maple Leaf Medical Clinic in Toronto; the Frederick National Laboratory for Cancer Research; 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 stick to a daily drug regimen. In addition, drugs may exhibit long-term side effects due to lifetime use and create the possibility of developing drug-resistant viruses. In previous research, single bNAbs have shown only limited success in keeping virus levels low, in part because bNAb-resistant HIV already exists or has emerged in the individual. To address this problem, researchers at the NIAID Laboratory of Immunoregulation tested a dual combination of bNAbs – called 3BNC117 and 10-1074 – targeting different parts of the HIV surface.
The researchers conducted a two-arm clinical trial between September 2018 and January 2021. The first arm was a randomized, placebo-controlled Phase 1 trial involving 14 HIV-positive participants. These people had started ART during the early phase of their infection. They were taken off antiretrovirals shortly following 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 therefollowing – 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 might suppress HIV in the absence of ART. None of the seven participants who received the bNAb treatment needed to restart ART until 28 weeks following the infusion, compared with six of the seven participants who received a placebo. The median duration of discontinuation of antiretrovirals was 39.6 weeks (bNAb group) and 9.4 weeks (placebo), respectively.
The second arm of the study involved bNAb infusions in a group of 5 study participants who were not taking antiretroviral therapy but still maintained low levels of HIV. In this small group, only two of five study participants maintained complete virus suppression for an average of 41.7 weeks following bNAb transfusions.
The authors note that the bNAb combination was ineffective in suppressing HIV if participants harbored virus resistant to one or both of the 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 arose in the study and the infusions were well tolerated.
The study authors conclude that bNAb combination therapy can be highly effective in suppressing HIV in the absence of ART for long periods of time, provided that antibody-resistant virus is not present at the time individuals start treatment. antibody treatment. Larger studies are needed to confirm the results, but as next-generation bNAbs with increased potency and durability become available, “there is reason to believe that infrequent administration (i.e. say twice a year) of these antibodies, possibly together with a long-acting injectable antiretroviral drug, might lead to suppression of HIV without antiretroviral therapy for long periods (years) in those infected,” the authors wrote. authors.
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