West Nile Virus in People with HIV: Immune Vulnerability, Neuroinvasive Disease, and Diagnostic Challenges

Abstract

West Nile virus (WNV) is an expanding mosquito-borne orthoflavivirus and an important cause of arboviral neuroinvasive disease. Whether HIV infection modifies WNV susceptibility, severity, or diagnostic performance remains uncertain. This narrative review was supported by structured PubMed/MEDLINE and Scopus searches updated to 22 August 2026 and a supplementary targeted citation search, identifying 23 peer-reviewed reports providing direct clinical or seroepidemiological evidence on WNV in people with HIV (PWH). The evidence remains heterogeneous, but recent data clarify several conclusions. A Northern Italian sero-repository study of 2843 PWH found neutralization-confirmed WNV antibodies in 3.0%, with no neuroinvasive disease and no association with HIV-related immunological variables. Comparative US cohorts likewise do not demonstrate that HIV status alone confers a uniform excess risk of WNV neuroinvasive disease. Conversely, individual reports of advanced HIV disease describe severe neuroinvasive presentations with delayed or absent WNV-specific antibody responses and molecular confirmation. HIV status alone should therefore not be considered a uniform WNV risk marker; the individual immune phenotype may be more clinically informative. In PWH with profound immunosuppression, negative early serology should not prematurely exclude WNV, and molecular testing should be considered when clinical suspicion remains high. Prevention, seasonal vigilance, and prospective HIV-specific studies remain priorities.