Combination anti-HIV antibody therapy can suppress virus for prolonged period, suggests NIH study
While the small study only included 19 participants, the findings offer hope that combination bNAb therapy might offer a future alternative to daily ART for people living with HIV.
Shortcomings of antiretrovirals
People with HIV require life-long antiretroviral therapy. Although oral antiretrovirals are highly effective at keeping HIV levels under control, it can be difficult for some people with HIV to adhere to the required daily medication regimen. Medicines can also present long-term side effects over lifetime usage and create the possibility for the development of drug-resistant virus.
As a result, there is a need to develop alternatives with long-lasting antiviral agents that can inhibit viral replication.
Single bNAbs have previously only shown limited success in keeping virus levels low: partly because bNAb-resistant HIV either already existed or emerged in the individual.
To address this problem, researchers in the NIAID Laboratory of Immunoregulation tested a dual combination of bNAbs (3BNC117 and 10-1074) targeting different parts of the surface of HIV.
The first component of the study was a Phase 1 randomized, placebo-controlled trial involving 14 participants with HIV, who had started ART during the early phase of their infection. They were taken off antiretrovirals shortly after receiving their first infusion of the combination bNAbs or placebo. Participants received up to 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 purpose of the study was to see if treatment with the bNAbs could suppress HIV in the absence of ART. None of the seven participants who received the bNAb treatment had to restart ART before 28 weeks post-infusion compared to six of the seven participants who received placebo. The median duration of time off antiretrovirals was 39.6 weeks (bNAb group) and 9.4 weeks (placebo), respectively.
The second component of the study involved bNAb infusions in a group of 5 study participants who were not taking ART but still maintained low levels of HIV. In this smaller group, only two of the five study participants maintained complete suppression of the virus for an average of 41.7 weeks following the bNAb transfusions.
The bNAb combination was ineffective in suppressing HIV if participants harbored virus resistant to either or both experimental antibodies before receiving the infusions: illustrating ‘major challenge’ of pre-existing antibody-resistant HIV, note the authors.
No safety issues occurred in the study, and the infusions were well-tolerated.
Combination bNAb therapy can 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 begin antibody treatment, conclude the authors.
Larger studies are needed to confirm the findings, but as next-generation bNAbs with increased potency and durability become available, “there is reason to believe that infrequent administration (i.e., twice a year) of such antibodies, possibly along with a long-acting injectable antiretroviral drug, could lead to ART-free HIV suppression for extended periods (years) in infected individuals,” write the authors.
The research, conducted between September 2018 and January 2021, was led 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 NIH Clinical Center; the Maple Leaf Medical Clinic in Toronto; the Frederick National Laboratory for Cancer Research; Harvard Medical School, Boston; and The Rockefeller University, New York City.
The study can be found here.
