U of A study seeks to understand factors that allow HIV to persist during antiretroviral therapy

Elizabeth Connick, MD, a professor of medicine and chief of the Division of Infectious Diseases in the Department of Medicine at the University of Arizona College of Medicine – Tucson, received a $703,000 grant as bridge funding from the National Institutes of Health for a study entitled, “Immune Microenvironments that Impact HIV Persistence and Expression During ART,” or antiretroviral therapy.

This digitally colorized image (right) depicts a single human immunodeficiency virus (HIV), as it was budding from a human immune cell, which the virus had infected, and within which the HIV virus had been replicated. (Credit: NIAID, 2012)

ART, which is recommended for everyone with HIV, involves taking a combination of HIV medicines every day. Human immunodeficiency virus, or HIV, is a retrovirus that attacks the body’s immune system, specifically CD4+ white blood cells. By destroying these cells, HIV weakens the body’s ability to fight infection and makes people more susceptible to other diseases, such as tuberculosis, fungal infections, and some cancers. ART interrupts HIV replication so people can live healthy and fulfilling lives. If ART is stopped, however, the virus rebounds and replication recurs. For this reason, ART must be taken lifelong to suppress HIV.

“The purpose of this work is to identify the factors in secondary lymphoid tissues that lead to continuous low-level expression of virus in people living with HIV who are receiving ART,” said Dr. Connick, principal investigator on the grant. Secondary lymphoid tissues such as lymph nodes, the spleen, tonsils, and gut-associated lymphoid tissues are the major reservoirs for HIV during ART.

“Cells in secondary lymphoid tissues are the major source of rebound viremia when ART is stopped. Understanding the factors that promote HIV expression during ART could lead to strategies to prevent viral rebound or alternatively to flush out these cells,” she added. In the long term, understanding these factors could lead to strategies for a “cure” or a “ART-free remission” of HIV.

Dr. Connick co-authored a paper related to this topic that appeared in the journal Virus Evolution in January. This research also was presented by Joy M. Folkvord, an investigator in Dr. Connick’s lab, at the 12th International AIDS Society Conference on HIV Science that took place in Brisbane, Australia, in July 2023 under the title: “Follicular T helper cells (TFH) are a minor source of the active HIV reservoir in secondary lymphoid tissues of people with HIV (PWH) on prolonged suppressive antiretroviral therapy (ART).”.

Antiretroviral therapy for HIV infection has changed dramatically in the past two decades. (Credit: NIAID, 2023)

Co-investigators on this latest grant include: Edward Bedrick, PhD, a professor in the Department of Epidemiology & Biostatistics at the U of A Mel and Enid Zuckerman College of Public Health; Matthew Ollerton, PhD, a Division of Infectious Diseases research scientist in the Department of Medicine at the College of Medicine – Tucson; Cecilia Shikuma, MD, of the University of Hawaii at Manoa; Matthew Reynolds PhD, of the University of Wisconsin-Madison; and Sara Gianella Weibel, MD, of the University of California, San Diego.

The NIH awarded funding for the study through the National Institute of Allergy and Infectious Diseases, an NIH unit, under NIH/NIAID Award Number R56AI181705.

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