T-cell activation state differentially contributes to neuropsychiatric complications in women with HIV

Neuropsychiatric complications are common among women with HIV (WWH). The pathophysiological mechanisms underlying these complications are not fully known but likely driven in part by immune modulation. We examined associations between T-cell activation states which are required to mount an effective immune response (activation, co-stimulation/normal function, exhaustion, senescence) and neuropsychiatric complications in WWH. 369 WWH (78% HIV RNA undetectable/<20cp/mL) enrolled in the Women's Interagency HIV Study completed neuropsychological testing and measures of depression (Center for Epidemiological Studies Depression Scale-CES-D), self-reported stress levels (Perceived Stress Scale-10), and post-traumatic stress (PTSD Checklist-Civilian Scale). Multiparametric flow cytometry evaluated T-cell activation state. Partial least squares regressions were used to examine T-cell phenotypes and neuropsychiatric outcome associations after confounder adjustment. In the total sample and among virally suppressed (VS)-WWH, CD4⁺ T-cell exhaustion was associated with poorer learning and attention/working memory (P's < 0.05). In the total sample, CD4⁺ T-cell activation was associated with better attention/working memory and CD8⁺ T-cell co-stimulation and senescence was associated with poorer executive function (P's < 0.05). For mental health outcomes, in the total sample, CD4⁺ T-cell activation was associated with more perceived stress and CD4⁺ T-cell exhaustion was associated with less depressive symptoms (P's < 0.05). Among VS-WWH, CD4⁺ senescence was associated with less perceive stress and CD8⁺ T-cell co-stimulation and senescence was associated with higher depression (P's < 0.05). Together, results suggest the contribution of peripheral CD4⁺ and CD8⁺ T-cell activation status to neuropsychiatric complications in WWH.