HIV antibodies for treatment of HIV infection

Abstract

The bar is high to improve on current combination antiretroviral therapy (ART), now highly effective, safe, and simple. However, antibodies that bind the HIV envelope are able to uniquely target the virus as it seeks to enter new target cells, or as it is expressed from previously infected cells. Furthermore, the use of antibodies against HIV as a therapeutic may offer advantages. Antibodies can have long half-lives, and are being considered as partners for long-acting antiretrovirals for use in therapy or prevention of HIV infection. Early studies in animal models and in clinical trials suggest that such antibodies can have antiviral activity but, as with small-molecule antiretrovirals, the issues of viral escape and resistance will have to be addressed. Most promising, however, are the unique properties of anti-HIV antibodies: the potential ability to opsonize viral particles, to direct antibody-dependent cellular cytotoxicity (ADCC) against actively infected cells, and ultimately the ability to direct the clearance of HIV-infected cells by effector cells of the immune system. These distinctive activities suggest that HIV antibodies and their derivatives may play an important role in the next frontier of HIV therapeutics, the effort to develop treatments that could lead to an HIV cure.

Keywords: ADCC; HIV; cure; entry inhibition; monoclonal antibodies.

Figure 1. Potential antiviral activity of neutralizing and non-neutralizing antibodies

Shown are potential sites of activity within the life cycle of HIV for neutralizing antibodies (opsonization or neutralization of free virus, ADCC of cells expressing HIV envelope during virus budding) or non-neutralizing antibodies (ADCC of cells during virus entry after envelope binding to CD4, ADCC of cells expressing HIV envelope during virus budding - if CD4 is encountered).