Overall, the story of HIV is one of astounding success. But to declare victory, it will be necessary to develop a vaccine. The opening session of the 31st Conference on Retroviruses and Opportunistic Infections (CROI) 2024 looked back to the failures but also the advances in research, all the steps that over the years brought the basic science knowledge that could bring an HIV vaccine in the future. This year, the former director of the Viral Pathogenesis Laboratory at the NIAID Vaccine Research Center, Barney Graham, was named for the Bernard Field Lecture, where he presented “Modern vaccinology: a legacy of HIV research.”

On March 4, 2024, several groups of scientists discussed the challenges of investigating the effects of HIV in the central nervous system (CNS) at the oral abstract session on neuropathogenesis of HIV held during the 31st Conference on Retroviruses and Opportunistic Infections (CROI), in Denver. A cure for HIV will require eliminating the virus in all its reservoirs, those tissues where HIV remains latent but retains the capacity for reactivation and replication. However, despite antiretroviral therapy (ART), the virus could continue to replicate continuously at a low level in some reservoirs, including the CNS.

An Italian group of researchers has used zinc finger editing to silence the PCSK9 gene and improve blood cholesterol levels in mice by applying a single dose of their modifier. The epigenetic-based method could be an alternative to genome editing.

Separate teams of investigators have reported new insights into how the brain disposes of metabolic waste via the glia-based lymphatic system, or glymph system. In two papers published in Nature on Feb. 28, 2024, scientists from Washington University in St. Louis described how in sleeping animals, the synchronized activity of neurons drove ionic gradients that facilitated the movement of fluid through brain tissue. And researchers from the Massachusetts Institute of Technology showed that, in a mouse model of Alzheimer’s disease (AD), the glymphatic system mediated clearance of amyloid-β after sensory stimulation at a 40-Hertz rhythm.

Autoantibodies call to mind disease – autoimmune disease, to be exact. But the physiological roles of autoantibodies are, at the very least, more complex than this view accounts for. “The autoantibody reactome is extraordinary,” Aaron Ring told BioWorld. “Nearly everyone has autoantibodies, whether they know it or not.”

Bruton tyrosine kinase (BTK) enzyme inhibitors used to treat B-cell cancers, including chronic lymphocytic leukemia and non-Hodgkin lymphoma, also produce resistance by causing mutations in the protein. Now, a study on the BTK degrader NX-2127 showed the compound could be effective in eliminating BTK regardless of its mutations.

Humans love to think of our species as unique. But on a genetic level, such uniqueness is surprisingly hard to find. And while that may be a blow to the ego, it also means that an evolutionary lens is one way to search for insights into human diseases. Animals are “adapted to use the same genes that you and I have, but in very different ways,” Ashley Zehnder told BioWorld. Zehnder is co-founder and CEO of Fauna Bio Inc., which uses comparative genomics to identify gene networks that underlie disease resistance in different animal species.

Investigators have identified five cases of so-called iatrogenic Alzheimer’s disease (AD), that is, AD that was acquired as a result of undergoing medical procedures. A team led by University College London scientists reported their findings online in Nature Medicine on Jan. 29, 2024.

Using interactions between viral peptides and human proteins as a starting point, researchers from Enyo Pharma Inc., the University of Lyon and other institutions were able to bootstrap themselves to a mitochondria-targeting small molecule that showed activity in a mouse model of nonalcoholic steatohepatitis (NASH) with chronic kidney disease.