We characterized the incidence, risk factors, and outcomes of both opportunistic (OI) and non-opportunistic (non-OI) CNS infections among people with HIV (PWH).

While the incidence of central nervous system (CNS) infections among PWH has declined with use of modern antiretroviral therapy (ART), CNS infections still cause significant morbidity among PWH. The clinical and epidemiological features of these infections in the modern ART era remain largely unknown.

A retrospective observational cohort study was conducted linking the clinical database at the Southern Alberta HIV Clinic (SAC) with regional laboratory database to identify definitive cases of CNS infection  from 1995-2019. CNS infection was categorized into OI (CMV, toxoplasmosis, PML and cryptococcal meningitis) and non-OI (EBV, coccidiomycosis, tuberculosis, neurosyphilis, HSV and VZV). Annual incidence rates (IR) of CNS infections per 1,000 person-years (PY) were calculated and collapsed into three time periods for OI and non-OI. Cox proportional hazards models were used to estimate hazard ratios(HR) and 95% confidence intervals ([,]) of risk factors for CNS infections in PWH.

Among 2,912 PWH in care, 132(4.5%) CNS infections were diagnosed including 104(78.8%) OI and 28(21.2%) non-OI. While the incidence of CNS OI declined significantly across all three time periods with minimal change was seen in incidence of CNS non-OI. Risk factors for CNS infections were a CD4+ nadir of <200cells/mm³ (HR=11.1 [4.4-47.7]), Black ethnicity (HR=1.9 [1.3, 2.8]) and more comorbidities, Charlson Comorbidity index of >4 (HR=21.1 [11.0-40.5]) compared to those with scores of 0. PWH with past CNS infection were less likely to be working, had higher neurologic comorbidities including seizures (HR=4.2 [2.6-6.6]) and stroke (HR=3.6 [1.82-7.04]) and a higher AIDS-related mortality (HR=5.7 [2.4-14.0]).

Although HIV-related CNS infections have continued to decline over time, associated morbidity remains high. Ongoing prevention and care for PWH following CNS infection need to improve.