Uncovering Novel Anti-HIV Factors
By Jeffrey Laurence, M.D.
Elite controllers, capable of suppressing HIV replication in the absence of antiretroviral therapy (ART), represent less than 1% of all HIV-positive individuals. While small in number, their participation in research studies has been critical to our understanding of how a functional cure for HIV might be achieved. Furthermore, while most studies of elite controllers have used peripheral blood, HIV growth occurs primarily in lymph nodes, raising the question: How might cells in those immune tissues contribute to viral suppression?
Dr. Steven DeeksamfAR-funded researchers investigated immune cells obtained from the lymph nodes of elite controllers. They compared them to cells obtained from “chronic progressors,” who are individuals with advancing HIV disease in the absence of ART. They found that CD8+ T cells—usually thought of as virus “killers”—isolated from elite controllers suppressed HIV replication without killing infected cells. This activity was associated with producing and releasing substances such as immune hormones or cytokines.
Researchers then investigated the range of cytokines each CD8+ T cell was capable of making in response to HIV. Cells that can make many different types of immune enhancing cytokines might be better able to suppress HIV than cells that make only one or two types.
Consistent with this assumption, researchers found that the cells of elite controllers were more likely than those of chronic progressors or HIV-positive individuals on ART to produce a wider range of cytokines. In fact, only CD8+ T cells from elite controllers were capable of making up to five different types of cytokines.
The authors argue that this finding is “highly pertinent” to guiding the search for a functional cure—achieving remission—of HIV. These investigations primarily focus on kill strategies, but should also consider antiviral factors, which suppress rather than kill the virus.
Dr. Steven Deeks, a co-author of the study, is a member of the amfAR Institute for HIV Cure Research at the University of California, San Francisco.
Dr. Laurence is amfAR’s senior scientific consultant.