HIV Infection and Sepsis Outcomes in the Antiretroviral Therapy Era: A Systematic Review

Sepsis remains a major cause of mortality, but whether human immunodeficiency virus (HIV) infection is independently associated with worse outcomes among adults with sepsis in the antiretroviral therapy (ART) era remains uncertain. We systematically reviewed observational studies comparing outcomes between adults with sepsis according to HIV status. PubMed/MEDLINE and Scopus were searched on 11 July 2026; the Cochrane Library and reference lists were also screened. A supplementary sensitivity search was conducted to identify eligible studies potentially missed by the primary search strategy. Eligible studies enrolled adults with study-defined sepsis from 1996 onward and included an HIV-negative comparator. Risk of bias was assessed using the Quality In Prognosis Studies (QUIPS) tool, and findings were synthesized descriptively because of clinical and methodological heterogeneity. Seventeen reports from eight countries were included, with analytic samples ranging from 58 patients to 74,020 hospitalizations for severe sepsis. Several studies reported higher mortality among patients with HIV in crude analyses, but findings were inconsistent after multivariable adjustment or matching. No included report had low risk of bias in the confounding domain. HIV-specific prognostic factors were incompletely characterized; limited evidence suggested that virological control may be more informative than HIV status alone. Overall, current evidence is insufficient to establish a consistent independent association between HIV status and sepsis mortality. Differences in HIV disease control, acute illness severity, infectious etiology, and adjustment strategies limit definitive inference. Contemporary prospective studies incorporating viral suppression, immune status, and standardized measures of sepsis severity are needed.