A multinational team led by Weill Cornell Medicine investigators developed a test that will help measure the persistence of HIV in people affected by viral strains found predominantly in Africa—a vital tool in the search for an HIV cure that will benefit patients around the world.
The study, published in Nature Communications on July 2, helps fill a major gap in human immunodeficiency virus (HIV) research. Most HIV studies have focused on strains circulating in Western countries, predominantly in men who have sex with men affected by subtype B. Few studies have examined strains circulating in Africa, where women are disproportionately affected.
“HIV cure research tends to focus on viral strains circulating in developed countries, but to achieve a cure that is globally applicable, we must study viral strains that are affecting other regions of the world,” said lead author Dr. Guinevere Lee, assistant professor of virology in medicine in the Division of Infectious Diseases and assistant professor of microbiology and immunology at Weill Cornell Medicine.
The findings show—like other studies in developed countries—that HIV strains circulating in Africa establish viral reservoirs in the human body. Although antiretroviral therapy can reduce the level of HIV in the blood to an undetectable level, these dormant reservoirs continue to survive.
They contain a large number of defective proviral DNA genomes which can’t produce new infectious viruses, but a small number of genomes remain genetically intact and ready to produce active viruses if antiretroviral treatment is interrupted.
The large proportion of defective viral genomes obscures researchers’ attempts to accurately quantify the copies of intact proviruses.
“We are looking for a needle in a haystack: To achieve an HIV cure, we need to first find out whether any genome-intact proviruses remain in the body during antiretroviral treatment. Our new assay allows us to do this. Then we need to target and eliminate the intact proviral DNA capable of producing new viruses,” Dr. Lee explained.
Broadening the lens of HIV research with a new assay
Dr. Lee and her colleagues analyzed DNA from immune cells called CD4+ T cells, where viral DNA hides, of 16 women and seven men receiving antiretroviral HIV treatment in Uganda. Genetic sequencing of the virus revealed two predominant HIV-1 subtypes: A1 and D (a notoriously aggressive strain). The study also identified viral hybrids of A1 and D.
The team then modified existing laboratory tests that identify HIV subtype B proviruses to detect proviruses that are subtypes A1 and D. “The new assay we’ve developed will help researchers home in on the intact proviral genomes relevant to HIV cure research for patients affected by these under studied strains,” Dr. Lee said.
Dr. Lee and her multinational, multi-institution collaborators are already using the new assay to study long-term viral persistence in Uganda. Their findings show that the composition of the HIV proviral genomic landscape is broadly comparable between subtypes A1, D and B suggesting that approaches to target intact HIV reservoirs in Africa will face similar “needle-in-a-haystack” challenges as in North America and Europe.
Future studies will also need to evaluate differences in non-B subtypes to understand whether subtype-specific factors impact persistence, reactivation or clearance in viral reservoirs.
Researchers from Simon Fraser University, Canada; British Columbia Center for Excellence in HIV/AIDS, Canada; Rakai Health Sciences Program, Uganda; University of Cape Town, South Africa; and Johns Hopkins University School of Medicine also contributed to this study.
More information: Lee, G.Q., et al. HIV-1 subtype A1, D, and recombinant proviral genome landscapes during long-term suppressive therapy. Nature Communications (2024). DOI: 10.1038/s41467-024-48985-9
News
Scientists discover natural ‘brake’ that could stop harmful inflammation
Researchers at University College London (UCL) have uncovered a key mechanism that helps the body switch off inflammation—a breakthrough that could lead to new treatments for chronic diseases affecting millions worldwide. Inflammation is the [...]
A Forgotten Molecule Could Revive Failing Antifungal Drugs and Save Millions of Lives
Scientists have uncovered a way to make existing antifungal drugs work again against deadly, drug-resistant fungi. Fungal infections claim millions of lives worldwide each year, and current medical treatments are failing to keep pace. [...]
Scientists Trap Thyme’s Healing Power in Tiny Capsules
A new micro-encapsulation breakthrough could turn thyme’s powerful health benefits into safer, smarter nanodoses. Thyme extract is often praised for its wide range of health benefits, giving it a reputation as a natural medicinal [...]
Scientists Develop Spray-On Powder That Instantly Seals Life-Threatening Wounds
KAIST scientists have created a fast-acting, stable powder hemostat that stops bleeding in one second and could significantly improve survival in combat and emergency medicine. Severe blood loss remains the primary cause of death from [...]
Oceans Are Struggling To Absorb Carbon As Microplastics Flood Their Waters
New research points to an unexpected way plastic pollution may be influencing Earth’s climate system. A recent study suggests that microscopic plastic pollution is reducing the ocean’s capacity to take in carbon dioxide, a [...]
Molecular Manufacturing: The Future of Nanomedicine – New book from Frank Boehm
This book explores the revolutionary potential of atomically precise manufacturing technologies to transform global healthcare, as well as practically every other sector across society. This forward-thinking volume examines how envisaged Factory@Home systems might enable the cost-effective [...]
New Book! NanoMedical Brain/Cloud Interface – Explorations and Implications
New book from Frank Boehm, NanoappsMedical Inc Founder: This book explores the future hypothetical possibility that the cerebral cortex of the human brain might be seamlessly, safely, and securely connected with the Cloud via [...]
Global Health Care Equivalency in the Age of Nanotechnology, Nanomedicine and Artificial Intelligence
A new book by Frank Boehm, NanoappsMedical Inc. Founder. This groundbreaking volume explores the vision of a Global Health Care Equivalency (GHCE) system powered by artificial intelligence and quantum computing technologies, operating on secure [...]
Miller School Researchers Pioneer Nanovanilloid-Based Brain Cooling for Traumatic Injury
A multidisciplinary team at the University of Miami Miller School of Medicine has developed a breakthrough nanodrug platform that may prove beneficial for rapid, targeted therapeutic hypothermia after traumatic brain injury (TBI). Their work, published in ACS [...]
COVID-19 still claims more than 100,000 US lives each year
Centers for Disease Control and Prevention researchers report national estimates of 43.6 million COVID-19-associated illnesses and 101,300 deaths in the US during October 2022 to September 2023, plus 33.0 million illnesses and 100,800 deaths [...]
Nanomedicine in 2026: Experts Predict the Year Ahead
Progress in nanomedicine is almost as fast as the science is small. Over the last year, we've seen an abundance of headlines covering medical R&D at the nanoscale: polymer-coated nanoparticles targeting ovarian cancer, Albumin recruiting nanoparticles for [...]
Lipid nanoparticles could unlock access for millions of autoimmune patients
Capstan Therapeutics scientists demonstrate that lipid nanoparticles can engineer CAR T cells within the body without laboratory cell manufacturing and ex vivo expansion. The method using targeted lipid nanoparticles (tLNPs) is designed to deliver [...]
The Brain’s Strange Way of Computing Could Explain Consciousness
Consciousness may emerge not from code, but from the way living brains physically compute. Discussions about consciousness often stall between two deeply rooted viewpoints. One is computational functionalism, which holds that cognition can be [...]
First breathing ‘lung-on-chip’ developed using genetically identical cells
Researchers at the Francis Crick Institute and AlveoliX have developed the first human lung-on-chip model using stem cells taken from only one person. These chips simulate breathing motions and lung disease in an individual, [...]
Cell Membranes May Act Like Tiny Power Generators
Living cells may generate electricity through the natural motion of their membranes. These fast electrical signals could play a role in how cells communicate and sense their surroundings. Scientists have proposed a new theoretical [...]
This Viral RNA Structure Could Lead to a Universal Antiviral Drug
Researchers identify a shared RNA-protein interaction that could lead to broad-spectrum antiviral treatments for enteroviruses. A new study from the University of Maryland, Baltimore County (UMBC), published in Nature Communications, explains how enteroviruses begin reproducing [...]
