Blood-Brain Barrier Impairment in Patients Living with HIV: Predictors and Associated Biomarkers

Despite the substantial changes resulting from the introduction of combination antiretroviral therapy (cART), the prevalence of HIV-associated neurocognitive disorders (HAND) remains substantial. Blood-brain barrier impairment (BBBi) is a frequent feature in people living with HIV (PLWH) and it may persist despite effective antiretroviral treatment. A cross-sectional study was performed in PLWH who underwent lumbar puncture for clinical reasons or research protocols and several cerebrospinal fluid biomarkers were studied. BBBi was defined as cerebrospinal fluid-to-serum albumin ratio (CSAR) >6.5 (<40 years) or >8 (>40 years). We included 464 participants: 147 cART-naive and 317 on cART. Male sex was prevalent in both groups (72.1% and 72.2% respectively); median age was 44 (38-52) years in naive and 49 (43-57) years in treated subjects. BBBi was observed in 35.4% naive and in 22.7% treated participants; the use of integrase inhibitors was associated with a lower prevalence (18.3 vs. 30.9%, p = 0.050). At multivariate binary logistic regression (including age and sex) nadir CD4 cell count (p = 0.034), presence of central nervous system (CNS) opportunistic infections (p = 0.024) and cerebrospinal fluid (CSF) HIV RNA (p = 0.002) in naive participants and male sex (p = 0.021), a history of CNS opportunistic infections (p = 0.001) and CSF HIV RNA (p = 0.034) in treated patients were independently associated with BBBi. CSF cells and neopterin were significantly higher in participants with BBBi. BBBi was prevalent in naive and treated PLWH and it was associated with CSF HIV RNA and neopterin. Systemic control of viral replication seems to be essential for BBB integrity while sex and treatment influence need further studies.

Automated summary

Despite the introduction of combination antiretroviral therapy, the prevalence of HIV-associated neurocognitive disorders remains high. Blood-brain barrier impairment is a common issue in people living with HIV and is associated with CSF HIV RNA and neopterin levels. Further studies are needed to explore the influence of sex and treatment on BBB integrity.