Afam Okoye, Ph.D.

Although combination antiretroviral therapy (ART) has significantly improved the life span of people living with human immunodeficiency virus (HIV), cART alone is not able to eradicate the infection. Despite its high efficiency, cART must be maintained for life to prevent the resumption of virus replication and disease progression. This lifelong treatment, however, brings both health side effects for treated individuals and a significant economic burden to society. Considering that nearly 35 million people worldwide currently live with HIV, it becomes evident the importance of developing novel therapeutic interventions that could facilitate complete and durable remission of HIV infection. Failure to cure HIV is in part due to long-lived CD4+ T cells carrying an integrated, replication-competent form of the viral genome. These latently-infected cells can persist for long periods of time and are believed to be preserved by homeostatic mechanisms. The focus of Okoye’s laboratory is to develop novel strategies aimed at eliminating these latently-infected cells with the goal of facilitating remission from virus replication after cART cessation. A few projects are highlighted below:

HIV latency disruption

One strategy that has been proposed to enhance immune recognition of latently-infected CD4+ T cells is the use of a latency-reversing agents (LRA) to induce viral gene expression in the presence of suppressive cART, a strategy often referred to as “kick and kill”. The goal of this approach is to facilitate the clearance of cells with reactivating viral reservoirs by either viral cytopathic effects or immune cell-mediated killing. To date, several LRAs have been identified that can increase latent viral gene expression in in vitro models of HIV latency and in primary CD4+ T cells isolated from cART suppressed individuals. However, only a few studies using LRAs in vivo have reported a significant increase in virus production. Dr. Okoye’s lab is actively engaged in evaluating novel LRAs for their potential to disrupt HIV latency in vivo.

Therapeutic HIV vaccination

In most HIV-infected individuals, post-cART immune-mediated control of HIV replication is often limited, in part, due to the lack of potent and sustained anti-viral CD8+ T cell responses that can effectively eliminate the vast majority of HIV-producing cells. To date, immunologic interventions that can elicit and maintain such potent cytotoxic T cell responses in cART-suppressed HIV infections are yet to be defined. One approach currently under intense investigation is the use of therapeutic vaccines to boost pre-existing immune responses in HIV+ individuals on suppressive cART and/or to generate completely new responses to epitopes not previously elicited by the virus. Dr. Okoye’s lab is evaluating the potential of a number of vaccine-platforms to enhance cellular immunity in the setting of a previously established, cART-suppressed infection, with the goal of establishing long-term control of HIV replication after cART cessation.

Biography

Dr. Okoye graduated from University of Nigeria, Nsukka with a B.Sc. in Microbiology in 1998. He then went on to Nottingham Trent University, UK, to receive a M.Sc. in Biotechnology in 1999. His Ph.D. was achieved in Virology from the University of Glasgow, Scotland in 2004. He is currently a Research Associate Professor at VGTI with a joint faculty appointment at the Oregon National Primate Research Center.

Key publications