HIV Disease Dynamics and Markers of Inflammation and CNS Injury During Primary HIV Infection and Their Relationship to Cognitive Performance

Abstract

Introduction:Early systemic and central nervous system viral replication and inflammation may affect brain integrity in people with HIV, leading to chronic cognitive symptoms not fully reversed by antiretroviral therapy (ART). This study examined associations between cognitive performance and markers of CNS injury associated with acute HIV infection and ART.Methods:HIV-infected MSM and transgender women (average age: 27 years and education: 13 years) enrolled within 100 days from the estimated date of detectable infection (EDDI). A cognitive performance (NP) protocol was administered at enrollment (before ART initiation) and every 24 weeks until week 192. An overall index of cognitive performance (NPZ) was created using local normative data. Blood (n = 87) and cerebrospinal fluid (CSF; n = 29) biomarkers of inflammation and neuronal injury were examined before ART initiation. Regression analyses assessed relationships between time since EDDI, pre-ART biomarkers, and NPZ.Results:Adjusting for multiple comparisons, shorter time since EDDI was associated with higher pre-ART VL and multiple biomarkers in plasma and CSF. NPZ scores were within the normative range at baseline (NPZ = 0.52) and at each follow-up visit, with a modest increase through week 192. Plasma or CSF biomarkers were not correlated with NP scores at baseline or after ART.Conclusions:Biomarkers of CNS inflammation, immune activation, and neuronal injury peak early and then decline during acute HIV infection, confirming and extending results of other studies. Neither plasma nor CSF biomarkers during acute infection corresponded to NP scores before or after sustained ART in this cohort with few psychosocial risk factors for cognitive impairment.

Plasma Biomarkers of Alzheimer Disease in Women With and Without HIV

“…Lower levels of Aβ42 and Aβ40 in CSF and plasma and decreases in those levels are associated with AD, cognitive decline, and psychiatric and behavioral symptoms in aging individuals without HIV . Some studies have reported no association with either plasma Aβ42 or Aβ40 levels in PLWH, specifically men who have sex with men and transgender women …”

“…HIV crosses the blood-brain barrier, activates microglia, and leads to neuroinflammation and neurodegeneration, resulting in the release of NFL . Published studies in cross-sectional samples of PLWH have reported higher NFL levels in association with lower NP, and no association between baseline levels of NFL and subsequent cognitive decline over 24 months or more in PLWH, including men who have sex with men and transgender women . Some reports indicate that impaired kidney function, more commonly observed among PLWH, may be associated with changes in blood NFL levels .…”

Immune Activation in Primary Human Immunodeficiency Virus: Influence of Duration of Infection, Treatment, and Substance Use

“…Of the 216 randomized participants, all participants with plasma biomarkers assessed at baseline or longitudinally through 24 weeks were included in this subanalysis. Participants were selected for biomarker analysis if they were co-enrolled in a related observational study that evaluated neurologic or reservoir outcomes [ 16 , 17 ], had near-complete samples at the selected timepoints, and started ART at the designated visit (either at enrollment in the immediate arm or at week 24 in the deferred arm).…”

HIV-1 infection of genetically engineered iPSC-derived central nervous system-engrafted microglia in a humanized mouse model

“…HIV-1 enters the brain during the first initial weeks of acute infection (17)(18)(19)(20) via transmigration of HIV-1 infected cells across the blood-brain barrier (BBB) (21)(22)(23). In the periphery, HIV-1 targets the CD4 + T cells and monocytes that then disseminate infection to other tissues and organs (21)(22)(23)(24)(25)(26).…”