Underlying herpes infection may have an impact on brain health in people with HIV (PWH), according to new data presented at the Conference on Retroviruses and Opportunistic Infections (CROI) 2026 Annual Meeting.

Although most PWH are also infected with herpes viruses, the impact of the resulting immune response on brain health disorders has not been well studied, wrote Scott L. Letendre, MD, the University of California San Diego, and colleagues.

Cerebrospinal fluid (CSF) biomarkers have been linked to latent herpes infection, particularly Epstein-Barr virus (EBV). The researchers conducted tests on PWH to look for signs of inflammation in both the blood and the brain. They measured peripheral blood mononuclear cells to check for cytomegalovirus (CMV) and EBV, as well as HIV DNA; they also measured CMV and EBV in plasma and 11 biomarkers in CSF.

The study population included 107 adults living with HIV. The mean age of the participants was 55 years, 83% were men, and most identified as either Black (41%) or White (51%). All participants were being treated with antiretroviral therapy. The primary outcome was the association between viral measures and CSF biomarkers.

Overall, nine CSF biomarkers known to be associated with Alzheimer’s disease, and other brain disorders were associated with at least one viral measure in the blood. They included amyloid-beta 1-42, soluble amyloid precursor protein alpha, interleukin-6, soluble CD14, protein carbonyls, soluble TNF receptors (sTNFR), neurofilament light-chain protein (NFL), monocyte chemoattractant protein-1, and total tau.

In a multivariate analysis, six biomarkers remained associated with at least one herpes virus measure. In a clustering analysis, a viral cluster of CMV immunoglobulin G (IgG), EBV IgG, and EBV DNA was significantly associated with a CSF cluster of NFL and sTNFR-II (P < .0001).

The findings were limited by several factors including the cross-sectional design and lack of independent validation, and therefore, should be interpreted with caution, the researchers wrote. However, the results indicate a link between latent herpes virus infections and CSF biomarkers in PWH. “This raises the possibility that antiviral interventions could benefit brain health,” they concluded.

Informing Interventions

“Latent herpes viruses have the potential to reactivate in people living with HIV which can lead to neuroinflammation and impact long-term brain health,” said Shirin Mazumder, MD, infectious diseases specialist and associate professor at the University of Tennessee Health Science Center, Memphis.

“The new study supports previous research implicating the presence of latent herpes virus infections in the CSF to central nervous system-associated disorders in people living with HIV,” said Mazumder, who was not involved in the study.

Additional studies are needed to assess how treatment of latent herpes viruses can prevent neurological decline and to determine whether treatment with antivirals can reverse any cognition-related issues, Mazumder noted.

In practice, identifying the presence and impact of latent herpes virus infections in the central nervous system of PWH may allow for interventions and treatment that can help to improve neuroinflammation and cognitive function, she said.

The study received no outside funding. The researchers had no financial conflicts to disclose. Mazumder had no financial conflicts to disclose.