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Breakthrough in HIV Research: Emory University’s Innovative Approach

Researchers from Emory University have achieved a notable milestone in HIV research by demonstrating unprecedented control over SIV (Simian Immunodeficiency Virus) replication and the reduction of viral reservoirs. This was made possible through a rigorous infection model combined with the interruption of antiretroviral therapy (ART). Their findings, which underscore the role of PD1 and IL-10 in regulating HIV persistence and immune dysfunction, were published in Nature Immunology.

“This represents a significant step forward in the quest for a potential cure for HIV, ultimately benefitting the 39 million individuals living with the virus globally,” stated Rafick Sekaly, PhD, the study’s lead investigator and co-director of the Martin Delaney Collaboratory for HIV Cure Research. He emphasized that their exploration of PD1 and IL-10 over the past 15 years has culminated in this innovative in vivo intervention utilizing nonhuman primates (NHPs). Sekaly, who serves as a professor and vice-chair of translational medicine in the Emory School of Medicine, noted that their enhanced understanding of these molecules could lead to better strategies not just for treating HIV but also for addressing certain cancers and chronic infections.

The study leveraged a detailed NHP model comprising 28 ART-treated, SIV-infected rhesus macaques, providing a robust platform for understanding the dynamics of SIV infection. Researchers Mirko Paiardini, PhD, and Zachary Strongin spearheaded the development of this model, which included immune-based interventions with anti-IL-10 and anti-PD-1 therapies. Following 14 months of ART, a cohort of the monkeys was treated with immunotherapy, and after 12 weeks, ART was discontinued. Remarkably, nine out of ten of the monkeys in the combination treatment group displayed durable viral control, lasting six months after treatment cessation.

In addition to co-leading the Martin Delaney Collaboratory focused on HIV eradication, Paiardini is also the division chief of Microbiology and Immunology at the Emory National Primate Research Center (NPRC). His work, along with his collaborators, emphasizes the vital role of strategic immunotherapy in managing chronic viral infections.

Strongin, now a senior scientist at Merck and a former member of Paiardini’s lab, played a crucial role in the collaboration. Merck’s involvement in the RID HIV and ERASE HIV Collaboratories has been significant, as they provided specific reagents targeting PD1 and IL-10 in the studies.

Bonnie Howell, PhD, Merck’s vice president for quantitative biosciences, reiterated the company’s commitment to advancing HIV research and translating scientific breakthroughs into impactful treatments.

Sekaly highlighted the importance of the collaborative effort between academic researchers and industry partners as essential for this study’s success. He noted that the partnership among scientists from RID HIV, ERASE HIV, and Merck exemplifies the overarching objectives of the Martin Delaney Collaboratories, which aim to accelerate the research towards an HIV cure by fostering resource-sharing and collaborative methodologies.

First author Susan Ribeiro, PhD, along with her bioinformatics team, utilized advanced systems biology techniques to delve deep into the immune response mechanisms at play. This holistic approach was crucial in uncovering the new immune-based mechanisms responsible for the impressive viral control achieved in the study. Ribeiro serves as an assistant professor in the Department of Pathology at Emory, while her team members contribute significantly to ongoing research initiatives.

According to Sekaly and Paiardini, many prior attempts to explore immune-based HIV cures lacked a detailed understanding of the mechanisms at work. This study’s depth of analysis allows for a more nuanced perspective, which will guide subsequent research efforts in the field.

The team is already laying the groundwork for future investigations aimed at further elucidating the pathways identified in this work, particularly focusing on innate immune responses, metabolic factors, and epigenetic influences on viral control post-treatment. Their goal is to formulate and assess interventions that could enhance immune responses capable of managing viral rebounds, possibly leading to sustainable control of HIV and SIV in the absence of ART.

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