Injection of anti-HIV mixed antibody to suppress the virus for a long time

Injection of anti-HIV mixed antibody to suppress the virus for a long time

Scanning electron micrograph of an HIV-infected H9 T cell. Credit: NIAID

HIV-infected individuals who were started on antiretroviral therapy (ART) in the early stages of infection achieved a prolonged period of HIV suppression without the use of antiretroviral therapy after receiving two HIV antibodies (bNAbs) , according to a small study published today in the journal. temper nature. The results suggest that bNAb combination therapy may provide a future alternative to daily antiretroviral therapy for people living with HIV. The research was conducted by scientists at the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, in collaboration with researchers at the National Institutes of Health Medical Center; Maple Leaf Medical Clinic in Toronto; Frederick National Cancer Research Laboratory; Harvard Medical School, Boston; and Rockefeller University, New York City.

Although oral antiretrovirals are very effective in keeping HIV levels in check, it can be difficult for some people with HIV to stick to a daily medication regimen. In addition, the drugs can cause long-term side effects from lifelong use and create the possibility of developing a drug-resistant virus. In previous research, single bNAbs showed only limited success in keeping virus levels low in part because bNAb-resistant HIV is either already present or has emerged in the individual. To address this issue, researchers at the NIAID Laboratory of Immunoregulation tested a dual combination of bNAbs — called 3BNC117 and 10-1074 — that target different parts of the HIV surface.

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 that included 14 participants with HIV. These individuals started ART during the early stage of infection. They were taken off the antiretrovirals shortly after they received their first infusion of either the bNAbs mix or the placebo. Participants received up to eight bNAb or placebo injections — two in the first month and once monthly thereafter — for 24 weeks. HIV levels and CD4 T-cell counts were measured every 2 weeks.

The purpose of the study was to find out whether treatment with bNAbs can suppress HIV in the absence of ART. None of the seven participants who received bNAb treatment had to restart ART before 28 weeks after the infusion compared to six of the seven participants who received placebo. The median duration of ARV discontinuation was 39.6 weeks (bNAb group) and 9.4 weeks (placebo), respectively.

The second component of the study involved injection of bNAb into a group of 5 study participants who were not on antiretroviral therapy but who still had low levels of HIV. 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 noted that the bNAb combination was ineffective in suppressing HIV if participants had carried a virus resistant to either or both experimental antibodies prior to receiving the injection. According to the authors, the existence of antibody-resistant HIV presents a major challenge ahead. There were no safety issues in the study, and the injection was well tolerated.

The study authors concluded that bNAb combination therapy can be highly effective in suppressing HIV in the absence of prolonged ART, provided that antibody-resistant virus is not present at the time individuals begin antibody therapy. Larger studies are needed to confirm the results, but as the next generation of bNAbs with increased efficacy and durability becomes available, “there is reason to believe that rare (i.e., twice a year) administration of such antibodies, possibly in combination with long-acting use of antibody drugs can result in parenteral antiretrovirals to antiretroviral-free inactivation of HIV for prolonged periods (years) in infected individuals.”

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more information:
Tae-Wook Chun, a combination of HIV antibodies that provides sustained viral suppression, temper nature (2022). DOI: 10.1038 / s41586-022-04797-9

Provided by the National Institutes of Health/National Institute of Allergy and Infectious Diseases

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2022-06-01 16:27:56

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