Immunotherapy and impact on tissue reservoirs

HIV infects a broad array of tissues throughout the body. Consequently, any successful HIV cure strategy will need to target tissue HIV reservoirs, in addition to peripheral blood. Here we review recent immunotherapy approaches for HIV cure, with a focus on their ability to target viral tissue reservoirs, including immune privileged sites like the central nervous system (CNS).

Recent clinical trials of immunotherapy for HIV cure have demonstrated viral control in a subset of participants. T cell therapies, especially chimeric antigen receptor (CAR) T cells that can be targeted to lymphoid tissue, are highly promising, as are monoclonal antibody therapies such as broadly neutralizing antibodies to suppress HIV viremia and immune checkpoint inhibitors to enhance immune function. Despite this success, the penetration of many of these agents into the CNS is limited, and this remains a barrier to more widespread success of these therapies.

Immunotherapies represent a promising path toward an HIV cure, however their ability to target viral reservoirs within tissues represents a major challenge. Combination approaches leveraging multiple immunotherapy strategies, and other agents to reduce the HIV reservoir will likely be required to achieve viral control in the absence of antiretroviral therapy.