Source-www.eatg.org
Antiretroviral therapies (ART) have revolutionized the management of HIV-1, allowing individuals to lead relatively normal lives by halting the replication of the virus. However, these treatments do not eliminate HIV from the body. Instead, the virus can remain dormant in a state known as “latency,” hidden within cells. If ART is stopped, latent HIV can reactivate, replicate, and potentially lead to acquired immunodeficiency syndrome (AIDS). To achieve a cure, researchers are focusing on strategies to awaken latent HIV and target it for destruction.
Groundbreaking Clinical Trial Results
A new clinical trial spearheaded by Dr. Cynthia Gay, MD, MPH, Associate Professor of Infectious Diseases, and Dr. David Margolis, MD, the Sarah Kenan Distinguished Professor of Medicine, Microbiology & Immunology, and Epidemiology at the UNC School of Medicine, has shown promising but modest progress. The study, which also involved Dr. Catherine Bollard, MD, from George Washington University, combined the drug vorinostat with immunotherapy to address latent HIV.
Vorinostat functions by inhibiting histone deacetylase, an enzyme that maintains the tight packaging of DNA in cells. By blocking this enzyme, vorinostat opens up the chromatin structure, thereby “waking up” dormant HIV and making it detectable to the immune system. The immunotherapy, led by Bollard’s team, involved expanding participants’ white blood cells in the lab to enhance their ability to attack HIV-infected cells before reinfusion.
Challenges and Future Directions
The study’s findings, published in the Journal of Infectious Diseases, revealed a small reduction in the HIV reservoir, but the results were not statistically significant. Dr. Margolis emphasized the need for improved methods to flush out and eradicate the virus. “We did show that this approach can reduce the reservoir, but the reductions were not nearly large enough. We need better strategies to address this issue,” he said.
Understanding Latent HIV Activation
Latent HIV resides in cells with its genetic material tightly packed. Vorinostat’s role in inhibiting histone deacetylase opens the chromatin structure, making latent HIV visible and vulnerable to the immune system. However, the drug’s effects are transient, lasting only a day per dose. Researchers are exploring ways to prolong the activation of latent HIV to enhance treatment efficacy.
Immunotherapy and HIV Reservoirs
The trial involved six participants who received multiple doses of vorinostat, followed by the extraction and expansion of their immune cells, which were then reinfused. While this approach had success with other viruses like Epstein-Barr and cytomegalovirus, the results for HIV were modest. Only one participant showed a noticeable decrease in HIV reservoir levels, and increasing the dose of engineered immune cells led to slight declines in three other participants. Despite these efforts, the overall impact was not substantial enough to draw definitive conclusions.
A Collaborative Effort
The study highlights the critical role of dedicated participants who have collaborated with Margolis’s team for years. Their ongoing commitment has been crucial for data collection and understanding the dynamics of the viral reservoir. “Their altruistic participation is vital to our progress,” Margolis noted.
Looking Ahead
Although the recent study did not achieve the desired results, it represents a step forward in HIV research. Scientists are committed to refining latency reversal strategies and exploring new approaches to achieve a functional cure for HIV. Continued research and innovation remain essential in the quest to eradicate this persistent virus.