The current standard of care for HIV patients is antiretroviral therapy (ART). ART is lifesaving and life improving, but ART is also a lifelong commitment. If ART is interrupted, then HIV disease resumes due to the latent HIV reservoir where latency is defined as a reversibly nonproductive state of infection of individual cells that retain the capacity to produce infectious virus particles. Currently, there is a major effort by scientists to develop HIV cure approaches also known as HIV eradication interventions designed to destroy the latent HIV reservoir. The latent HIV reservoir is challenging to eradicate because latent HIV persisting as replication competent, transcriptionally silent provirus must be activated before it can be targeted for destruction. This Jens Christian Skou Fellowship project is focused on HIV latency in the intestines. Because the intestines are a site of major HIV-induced pathologies, understanding the intestinal HIV reservoir is an essential prerequisite for the successful tissue of targeting latency activating agent such that HIV eradication can be achieved.
The OVERALL PROJECT AIM is to characterize the intestinal latent HIV reservoir in patients undergoing ART. To accomplish this goal, CD4+ T cell subsets isolated from intestinal biopsies will be assayed for the presence of replication competent latent HIV. Completing this project will fill a critical knowledge gap regarding the systemic nature of the latent HIV reservoir and progress the field towards a cure for HIV infection.
Paul W. Denton is an AIAS Jens Christian Skou Fellow. He earned his Ph.D. in Immunology from the University of Texas Southwestern Medical Center at Dallas in 2008. His thesis research topic was HIV transmission and the prevention of transmission in humanized mice. Paul went on to study HIV latency and to evaluate the in vivo efficacy of antivirals in humanized mice as a research instructor at the University of North Carolina at Chapel Hill. In January 2014, Paul joined the faculty at Aarhus University where he conducts patient-based research into HIV latency with a focus on virus persistence in the intestines