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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. [ABSTRACT FROM AUTHOR]

HIV patients responding to antiretroviral therapy (ART) have a high burden of cytomegalovirus (CMV) and display accelerated cardiovascular change assessed systemically. We assessed the effects of HIV, ART and CMV on retinal artery calibers (RAC), as a non-invasive measure of vasculopathy in HIV patients beginning ART. We analysed 79 HIV patients beginning ART in Jakarta, Indonesia, with a median (range) age of 31 (19–48) years. RAC was assessed using Image J software from fundus photos of both eyes, before ART (V0) and after 3–12 months (V3–V12). CMV DNA and antibodies were assessed. Systemic vascular pathology was assessed by carotid intima media thickness (cIMT). Multivariable models assessed which variables best predicted RAC values at V12. HIV patients had narrower retinal arteries and higher levels of CMV antibodies than healthy controls. RAC decreased over 12 months of ART (p < .0001). Right RAC correlated with CMV IE-1 antibody, while the left RAC at V3 correlated with cIMT. Multivariable models linked RAC at V12 with detectable HIV RNA at V12 and declared use of alcoholic drinks, while a smoking habit was protective. Decreases in RAC in HIV patients responding to ART suggest progressive microvascular change distinct from changes assessed in large vessels. Correlations with CMV IE-1 antibodies suggest the decline in RAC may be accelerated by frequent reactivations of CMV. This may be a feature of severe HIV disease before ART, confirmed by associations with high baseline HIV RNA in multivariable models. Links with alcohol consumption and smoking testify to a complex pattern of modifiable risk factors. [ABSTRACT FROM AUTHOR]

Altered T cell profiles have been linked with metrics of persistent cytomegalovirus (CMV) infections in healthy aging and older HIV patients stable on antiretroviral therapy (ART). In this study, we use CMV DNA to identify active infections, and levels of CMV-reactive antibody to assess the persistent burden of CMV in a longitudinal study of 78 young adult patients beginning ART in Jakarta, Indonesia, with <200 CD4 T cells/ μ L. CMV antibodies, inflammatory markers (C-reactive protein [CRP], soluble interferon- α / β receptor) and T cell phenotypes were assessed before ART (V0) and after 1, 3, 6, and 12 months (V1–V12). CMV DNA was detected in 41 patients (52%) at V0, irrespective of CD4 T cell counts, gender, age, or plasma HIV RNA. CMV DNA+ patients had higher levels of antibody reactive with CMV Immediate Early 1 (IE-1) at V0 and V12 ( p  = 0.04), and with CMV lysate at V12 ( p  = 0.01). Detectable CMV DNA did not align with inflammatory markers, but associated with lower CD4/CD8 ratios until V3. CMV antibody levels correlated inversely with proportions of naive CD4 and CD8 T cells, and directly with proportions of CD57+ and activated memory T cells (CD3+ CD45RA−) after 3–12 months on ART. Overall, active CMV replication is common in HIV patients beginning ART in Indonesia and associates with low CD4/CD8 ratios. Elevated levels of CMV-reactive antibody measured on ART also mark a depletion of naive T cells, accumulation of memory T cells, and may be a stable metric of the burden of CMV. [ABSTRACT FROM AUTHOR]

Cytomegalovirus (CMV) affects γδ T-cell profiles in healthy individuals and transplant recipients, but the effects of HIV and CMV have not been distinguished in HIV patients. CMV-seropositive Indonesian HIV patients (n = 40) were studied before ART and after six months, alongside healthy controls (n = 20). 50% of patients started ART with detectable CMV DNA. Proportions of Vδ2− γδ T-cells were high in patients and declined on ART, whilst proportions of Vδ2+ γδ T-cells were uniformly low, and correlated inversely with levels of CMV DNA and CMV-reactive antibody. Residual Vδ2+ cells were enriched for markers of terminal differentiation, but this did not associate with CMV metrics. Patients with CMV DNA at baseline showed a direct correlation between CMV reactive-antibody and CD8+ γδ T-cells. Our data are consistent with a role for CMV in the depletion of Vδ2+ γδ T-cells in HIV patients beginning ART, with no consistent evidence of a role for CMV in γδ T-cell activation or differentiation. • Proportions of Vδ2+ / Vδ2− γδ T-cells were inversed in HIV patients. • Reduced percentages of Vδ2+ γδ T-cell in HIV patients correlated with metrics of their burden of CMV • Vδ2+ cells in patients were enriched for markers of terminal differentiation, but this did not associate with CMV metrics. • Patients with CMV DNA at baseline showed a direct correlation between CMV reactive-antibody and CD8+ γδ T-cells. [ABSTRACT FROM AUTHOR]