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Super antibodies – bear in mind

As mentioned earlier in this issue of TreatmentUpdate, there are several super antibodies (also known as broadly neutralizing antibodies, or bNAb) in development. These are antibodies that have been designed to be highly specific at attaching to HIV and preventing it from infecting cells. They are all experimental and have not been approved for HIV treatment or prevention. In clinical trials, some of these super antibodies can help keep HIV suppressed, at least for a time.

The best role for super antibodies is not yet known and many clinical trials lie ahead. One advantage is that they only need to be administered every six months, usually by intravenous infusion.

Below are some points to bear in mind about super antibodies:

Screening

Prior to using them, people will need to be screened for HIV that is susceptible to the antibodies. If the antibodies are approved, the cost of screening will need to be relatively cheap or be borne by the pharmaceutical company.

Cost

Highly specific and effective antibodies have been developed for inflammatory conditions (such as arthritis, Crohn’s and colitis, psoriasis) and cancer. In these cases, pharmaceutical companies charge high prices for these therapies. If bNAbs are ever approved for HIV prevention and treatment, it is not clear how much they will cost.

Administration

Antibodies need to be given intravenously or via subcutaneous injection (just under the skin). Some people prefer not to experience injections, so it is not clear how widely used antibody-based therapy will become. 

One, two or three?

How many antibodies are optimal? HIV can mutate quickly inside infected cells and develop resistance to one antibody. Therefore, super antibodies may be prioritized for people whose viral load is already suppressed or otherwise low. It is likely more difficult for HIV to easily develop resistance to two or more antibodies when used simultaneously. What is not known is the optimal number of super antibodies that should be administered to people. Should infusions include at least two or three antibodies, all given on the same day?

A virus that can hide

HIV-infected cells can lie deep within parts of the brain and lymphoid organs such as the spleen and testicles. It may be difficult for high concentrations of these antibodies to accumulate in the brain, spleen and certain other parts of the body. Thus, when super antibodies are used as part of treatment, they will likely need to be accompanied by anti-HIV drugs that can penetrate the brain, spleen and other reservoirs for the virus.

Super antibodies are also being developed to be used as part of efforts to try to cure HIV. In clinical trials, super antibodies will be part of several different approaches to curing this viral infection. Such trials are in their infancy, and the best combination of experimental drugs to use together with super antibodies in cure research is not clear.

Super antibodies are an exciting development, but studies are needed to explore the issues mentioned above and more.

—Sean R. Hosein

REFERENCES:

  1. Waters L, de Miguel-Buckley R, Poulin S, et al. Broadly neutralizing antibodies for human immunodeficiency virus treatment: Broad in theory, narrow in reality. Clinical Infectious Diseases. 2023 Mar 21;76(6):1136-1141. 
  2. McMyn NF, Varriale J, Fray EJ, et al. The latent reservoir of inducible, infectious HIV-1 does not decrease despite decades of antiretroviral therapy. Journal of Clinical Investigation. 2023 Sep 1;133(17):e171554. 
  3. Banga R, Perreau M. The multifaceted nature of HIV tissue reservoirs. Current Opinion in HIV/AIDS. 2024 May 1;19(3):116-123. 
  4. Keele BF, Okoye AA, Fennessey CM, et al. Early antiretroviral therapy in SIV-infected rhesus macaques reveals a multiphasic, saturable dynamic accumulation of the rebound competent viral reservoir. PLoS Pathogens. 2024 Apr 9;20(4):e1012135.
  5. Wang M, Yoon J, Reisert H, et al. HIV-1-infected T cell clones are shared across cerebrospinal fluid and blood during ART. Journal of Clinical Investigation Insight. 2024 Apr 8;9(7):e176208. 
  6. Kufera JT, Armstrong C, Wu F, et al. CD4+ T cells with latent HIV-1 have reduced proliferative responses to T cell receptor stimulation. Journal of Experimental Medicine. 2024 Mar 4;221(3):e20231511. 
  7. Kumar MR, Fray EJ, Bender AM, et al. Biphasic decay of intact SHIV genomes following initiation of antiretroviral therapy complicates analysis of interventions targeting the reservoir. Proceedings of the National Academy of Sciences USA. 2023 Oct 24;120(43):e2313209120.  
  8. Board NL, Yuan Z, Wu F, et al. Bispecific antibodies promote natural killer cell-mediated elimination of HIV-1 reservoir cells. Nature Immunology. 2024 Mar;25(3):462-470. 
  9. Lim SY, Lee J, Osuna CE, et al. Induction of durable remission by dual immunotherapy in SHIV-infected ART-suppressed macaques. Science. 2024 Mar 8;383(6687):1104-1111.