Broadly Neutralizing Antibodies - Broad in Theory, Narrow in Reality

[Jim Allen]

Aidsmap full writeup: https://www.aidsmap.com/news/nov-2022/do-broadly-neutralising-antibodies-really-have-future-treating-hiv

In Short:

Do broadly neutralising antibodies really have a future in treating HIV?

Although much research is currently exploring how broadly neutralising antibodies may help prevent, treat, or cure HIV, some scientists suggest that without substantially improving their performance, the antibodies’ future role in treating HIV may be scant.

Dr Laura Waters, chair of the British HIV Association, Dr José Arribas, former chair of the  European AIDS Clinical Society's HIV treatment guidelines panel, and colleagues coauthored the commentary. Specifically, they argue that a lack of clarity surrounding appropriate combinations of antibodies, the need for resistance testing, and poor penetration into anatomical reservoirs conspire to make broadly neutralising antibodies less practical than ART.


The combination of 3BNC117 and 10-1074 has been the most widely tested mixture, according to the authors. In one test, the combination didn’t produce persistent viral undetectability in three of four people who responded to the treatment, but the person who started the study with the lowest viral load (under 1000 copies) maintained a viral load of under 20 copies for over eight weeks. Everyone who participated in this study developed some degree of resistance to one of the two antibodies. In another trial, out of 17 people who received up to seven infusions of the same two antibodies, 13 maintained viral suppression without ART for 20 weeks and some for longer.

In summary, some antibody therapies have been shown to delay viral rebound in the absence of ART, but none have prevented it completely (although one person has maintained undetectable viral loads without ART for four years after taking an antibody treatment). Waters and her colleagues also point to other studies showing that broadly neutralising antibodies have no significant impact on reducing the size of the latent reservoir, which is required to truly eradicate HIV from someone’s body.

Ultimately, the authors conclude that given the current standards of ART, broadly neutralising antibodies are unlikely to be used as a first-line treatment for HIV without eliminating the need to conduct resistance screening and overcoming the barrier of maintaining long-term viral suppression. Because ART effectiveness is so high and rates of virologic failure in people taking it are so low, Waters and her colleagues write that demonstrating superior efficacy in neutralising antibodies would currently be “nigh on impossible.”

Laura Waters, Rosa de Miguel-Buckley, Sébastien Poulin, Jose R Arribas, Broadly Neutralizing Antibodies for HIV Treatment: Broad in Theory, Narrow in Reality, Clinical Infectious Diseases, 2022;, ciac835, https://doi.org/10.1093/cid/ciac835