CROI 2024: New Insights into HIV's Neuropsychiatric Complications
Background
Despite significant advances in antiretroviral therapy (ART), people with HIV (PWH) continue to experience a range of neuropsychiatric complications, including cognitive impairment, mood disorders, and cerebrovascular disease. These issues profoundly impact quality of life and present ongoing challenges for clinical management and research. This comprehensive review summarizes the most impactful findings presented at the 2024 Conference on Retroviruses and Opportunistic Infections (CROI), shedding light on the underlying mechanisms, risk factors, and emerging therapeutic strategies for these persistent neurological and mental health challenges in PWH.
Results
The conference highlighted significant advancements across several domains, revealing the complex interplay of factors contributing to neuropsychiatric complications in PWH. New evidence demonstrated active HIV RNA transcription in cerebrospinal fluid (CSF) cells (the fluid surrounding the brain and spinal cord) and brain tissue, even in individuals on virally suppressive antiretroviral therapy (ART), indicating persistent viral activity within the CNS. Linkages were established between neuropsychiatric complications or brain imaging findings in people with HIV and several critical factors: carotid artery inflammation and cerebrovascular disease, Alzheimer's disease genetic risk, social determinants of health (including pollution exposure), and epigenetic aging (changes in gene expression without altering DNA sequence).
Why It Matters
These findings underscore the critical need for continued research into HIV's impact on the central nervous system, even in the era of effective ART, and highlight the multifaceted nature of neuropsychiatric complications. The identification of persistent viral activity in the brain suggests that current treatments may not fully eradicate CNS reservoirs, potentially contributing to ongoing neurocognitive decline and neuropsychiatric symptoms. Understanding these complex mechanisms and developing targeted interventions could lead to novel strategies for preventing and treating these debilitating complications, significantly improving the long-term health and quality of life for people with HIV. Future research will likely focus on Phase II and Phase III human trials for promising compounds like tesamorelin and telmisartan, as well as developing new CNS-penetrant antiretrovirals and adjuvant therapies to address HIV persistence and neuroinflammation.