Association between circulating exhausted CD4+ T cells with poor meningococcal C conjugate vaccine antibody response in HIV-infected children and adolescents

OBJECTIVES: To investigate the expression levels of surface markers of activation (CD38 and HLA-DR), inhibition (PD-1, TIGIT and CD57) and co-stimulation (CD28 and CD127) on CD4+ T cells of children/adolescents with vertical HIV infection (HI patients) and HIV-uninfected (HU) controls vaccinated with the meningococcal C conjugate vaccine (MCC). METHODS: HI patients (n=12), aged 8-17 years, were immunized with two MCC injections, while HU controls (n=9), aged 5.3-10.7 years, received a single MCC dose (as per national recommendation at the time of this study, a single MCC vaccine dose should be given for healthy children and youth aged 1-18 years). The HI patients were categorized according to the combined antiretroviral therapy (cART) treatment. Blood samples were obtained before vaccination, after priming, and after the administration of a booster dose of vaccine to determine the serum bactericidal antibody (SBA) titers and the expression levels of surface markers on CD4+ T cells by flow cytometry. The levels of serum cytokines, IL-4 and CXCL-13 were also measured using Luminex kits. RESULTS: The co-expression of the TIGIT-HLA-DR-CD38 molecules increased in the CD4+ T cells of HI patients/no-cART who also showed a lower frequency of CD127+CD28+ CD4+ T cells than HI patients/cART and HU group subjects. There were significant negative correlations between the frequency of exhausted CD4+ T cells and the SBA response. IL-4 levels were higher in HI patients/cART and positively correlated with SBA titers but negatively associated with the expression of exhaustion markers. Moreover, the CXCL-13 levels were positively correlated with the exhausted CD4+ T cells. CONCLUSION: The results of our study suggest that the co-expression of exhaustion markers and/or loss of co-stimulatory molecules influence the SBA response in HI patients.

Prevalence of lipodystrophy and risk factors for dyslipidemia in HIV-infected children in Brazil

The aim of present study was to describe the frequency of lipodystrophy syndrome associated with HIV (LSHIV) and factors associated with dyslipidemia in Brazilian HIV infected children. HIV infected children on antiretroviral treatment were evaluated (nutritional assessment, physical examination, and laboratory tests) in this cross-sectional study. Univariate analysis was performed using Mann-Whitney test or Fisher's exact test followed by logistic regression analysis. Presence of dyslipidemia (fasting cholesterol >200 mg/dl or triglycerides >130 mg/dl) was the dependent variable. 90 children were enrolled. The mean age was 10.6 years (3-16 years), and 52 (58%) were female. LSHIV was detected in 46 children (51%). Factors independently associated with dyslipidemia were: low intake of vegetables/fruits (OR = 3.47, 95%CI = 1.04-11.55), current use of lopinavir/ritonavir (OR = 2.91, 95%CI = 1.11-7.67). In conclusion, LSHIV was frequently observed; inadequate dietary intake of sugars and fats, as well as current use of lopinavir/ritonavir was associated with dyslipidemia.