γδ T Cell Subpopulations Associate with Recovery of Memory Function in Indonesian HIV Patients Starting Antiretroviral Therapy

Abstract

Cognitive impairment may persist in HIV patients despite effective antiretroviral therapy (ART). However, recovery is influenced by the neurocognitive domain tested, the severity of HIV disease, and by education. In young adult patients commencing ART in Jakarta, Indonesia, we described improvements in all cognitive domains except memory after 6–12 months on ART. In this study, we address relationships between cytomegalovirus (CMV), γδ T cell profiles and neurocognitive assessments with a focus on memory. The JakCCANDO (Jakarta CMV Cardiovascular ART Neurology Dentistry Ophthalmology) project recruited patients (aged 18–48 years) beginning ART with <200 CD4⁺ T cells/μL. Cognitive assessments used validated tests of five domains. Flow cytometry was used to assess proportions of Vδ2⁻ and Vδ2⁺ γδ T cells, and their activation (HLA-DR) and terminal differentiation (CD27⁻/CD45RA⁺). All patients carried high levels of antibodies reactive with CMV, so the detection of CMV DNA before ART was used to stratify participants into subgroups with a moderate/high or an extremely high burden of CMV. Patients had higher proportions of Vδ2⁻ γδ T cells and fewer Vδ2⁺ γδ T cells than healthy controls before ART and at 6 months. Z-scores for memory function correlated with proportions of Vδ2⁺ γδ T cells at both time points. Linear regression analyses confirmed this association. When the detection of CMV DNA was used to stratify the cohort, the association between memory Z-scores and Vδ2⁺ γδ T cells or CMV antibodies was only discernible in patients with a lower CMV burden. Hence, CMV and Vδ2⁺ γδ T cells warrant further consideration as factors that may contribute to the poor recovery of memory on ART.