The use of an anti-HIV antibody combination during antiretroviral therapy (ART) interruption has an effect on the immune system of individuals who are HIV-positive, according to a study published in Nature Medicine.

Most individuals living with HIV can control the virus with ART. Although this medication is highly effective, the presence of latent viral reservoirs in the bodies of patients means that they require lifelong therapy. Previous studies have demonstrated that an immunotherapy combining 2 anti-HIV antibodies can also suppress HIV, similar to ART.

The authors of the current study examined the injection of these potent anti-HIV antibodies, known as neutralizing antibodies, and found an association with enhanced T cell responses that specifically recognize the virus. The study shows an unsuspected interaction and a potential influence between 2 arms of the human immune system: humoral immunity (antibodies) and cell-mediated immunity (T cells).

“It is really a proof of concept,” said Daniel E. Kaufmann, MD, a researcher at the University of Montreal Hospital Research Center and professor at the University of Montreal. “Here, we analyzed blood samples from participants in a clinical trial conducted by our collaborators that used laboratory-produced monoclonal antibodies to block the virus. All participants maintained viral suppression for at least 15 weeks after the ART therapy was stopped.”

Two days before their ART therapy was halted, 9 participants living with HIV who had viruses sensitive to antibodies received a first injection of a 2-antibody cocktail. Recruited by the international research team, this cohort of individuals received new injections of antibodies after 3 and 6 weeks of follow-up. Blood tests were carried out weekly to check whether the virus had returned.

Using cell analysis techniques, Julia Niessl, first study author and a doctoral student in Kaufmann’s lab, observed that the activity level of CD4 and CD8 T cells responding specifically to HIV was augmented during the period of antibody therapy combined with ART interruption.

Antibodies work differently than drugs—they are not passive. In addition to blocking the virus, antibodies engage and influence the immune system. Researchers documented the increase of the T cell immune response on 9 study participants who were HIV positive. But whether the T cell responses were more effective at controlling HIV than before the intervention has yet to be determined.

“In the future, this kind of antibody therapy will be studied in larger clinical trials for HIV prevention and treatment, as antibodies are very well tolerated by humans and can effectively block the virus for many weeks,” Kaufmann said.

Reference
  1. Niessl, J., Baxter, A.E., Mendoza, P. et al. Combination anti-HIV-1 antibody therapy is associated with increased virus-specific T cell immunity. Nat Med (2020). https://doi.org/10.1038/s41591-019-0747-1. Accessed February 5, 2020.