Early HIV Infection Linked to Nervous System Inflammation

Cerebrospinal fluid samples show signs of inflammation in people with new HIV infections.

Published on Mar. 9, 2026

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A new study presented at the Conference on Retroviruses and Opportunistic Infections (CROI) 2026 found that cerebrospinal fluid (CSF) samples from individuals with early HIV infection already showed signs of inflammation compared to samples from individuals without HIV. The researchers examined CSF samples from 14 adult men with primary HIV before they began antiretroviral therapy and compared them to 20 men without HIV. The findings suggest the importance of early initiation of HIV treatment to minimize potential complications from neuroinflammation, including the possibility of long-term cognitive issues.

Why it matters

Understanding the central nervous system pathology in the early stages of HIV infection has been limited, but this study provides further insight into the early effects of neuroinflammation in people living with HIV. The results support previous research indicating early invasion of the central nervous system in people with HIV and highlight the need for prompt treatment to mitigate potential complications.

The details

The researchers used an assay and heatmap to identify the 500 most variable proteins in the CSF samples at timepoints with more than three samples between baseline and 12 months. A total of 97 proteins immediately distinguished the people living with HIV from the control participants, and the proteins evolved in the untreated participants over time during early infection. The researchers observed enrichment in several pathways related to immune regulation and signaling, including neutrophil degranulation, interleukin signaling, and interactions between lymphoid and nonlymphoid cells.

  • The participants were enrolled in the study 160 days after HIV acquisition and followed for 48 visits.
  • The CSF samples were collected before the participants began antiretroviral therapy.

The players

Serena Spudich

The Gilbert H. Glaser Professor of Neurology at the Yale School of Medicine, Yale University in New Haven, Connecticut, and the lead researcher on the study.

Phillip Chan

A researcher at the Yale School of Medicine who has previously collaborated with Spudich on identifying early invasion of the central nervous system in people living with HIV.

Shirin Mazumder

An infectious diseases specialist and associate professor at The University of Tennessee Health Science Center in Memphis, Tennessee, who was not involved in the study but provided commentary on the findings.

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What they’re saying

“The new data support previous research by Spudich and colleague Phillip Chan, MB ChB, PhD, MRCP, Yale School of Medicine, identifying early invasion of the central nervous system in PWH.”

— Shirin Mazumder, Infectious diseases specialist and associate professor (Medscape Medical News)

“In practice, the findings highlight the importance of early initiation of antiretroviral therapy for HIV to minimize any potential complications from neuroinflammation, including the possibility of long-term cognitive issues.”

— Shirin Mazumder, Infectious diseases specialist and associate professor (Medscape Medical News)

What’s next

Additional studies including a more diverse and larger population are needed to further evaluate the effects of central nervous system immune dysfunction in early HIV.

The takeaway

This study provides further evidence of the importance of early identification and treatment of HIV to mitigate the potential neurological complications associated with the early stages of the infection. Prompt antiretroviral therapy can help minimize inflammation and damage to the central nervous system.