ABSTRACT
Persistent immune activation characterises HIV infection and is associated with depletion of CD4+ T-cells and increased risk of disease progression. Early loss of gut mucosal integrity results in the translocation of microbial products such as lipopolysaccharide (LPS) into the systemic circulation. This is an important source of on-going immune stimulation. The purpose of this study was to determine levels of CD4+ T-cell activation (%CD25 expression) and apoptosis (% annexin V/7-AAD) in asymptomatic, untreated HIV infection at baseline and after stimulation with LPS and incubation with or without vitamin C and N-acetylcysteine. LPS induced a significant (P < 0.03) increase in %CD25 expression, annexin V, and 7-AAD in HIV positive individuals. NAC in combination with vitamin C, significantly (P = 0.0018) reduced activation and early apoptosis of CD4+ T-cells to a greater degree than with either antioxidant alone. Certain combinations of antioxidants could be important in reducing the harmful effects of chronic immune activation and thereby limit CD4+ T-cell depletion. Importantly, we showed that CD4+ T-cells of the HIV positive group responded better to a combination of the antioxidants at this stage than those of the controls. Therefore, appropriate intervention at this asymptomatic stage could rescue the cells before repetitive activation results in the death of CD4+ T-cells.
Subject(s)
Antioxidants/pharmacology , Apoptosis/drug effects , Apoptosis/immunology , CD4-Positive T-Lymphocytes/drug effects , CD4-Positive T-Lymphocytes/immunology , HIV Infections/immunology , HIV-1/immunology , Adult , Annexin A5/metabolism , Asymptomatic Diseases , Biomarkers/metabolism , CD4 Lymphocyte Count , CD4-Positive T-Lymphocytes/metabolism , CD4-Positive T-Lymphocytes/virology , Case-Control Studies , Cells, Cultured , Cross-Sectional Studies , Female , HIV Infections/virology , Humans , Interleukin-2 Receptor alpha Subunit/metabolism , Lipopolysaccharides/immunology , Lymphocyte Activation/drug effects , Lymphocyte Activation/immunology , Male , Viral Load , Young AdultABSTRACT
INTRODUCTION: Cardiovascular disease and thrombotic events have emerged as major causes of mortality in people living with HIV. Activated platelets play a key role in both inflammation and thrombosis. Haematology analysers measure a variety of platelet indices, which could be surrogate markers of platelet activation. Flow cytometry offers the discrimination of platelet subpopulations and evaluation of the activation status of platelets. This study aimed to measure platelet indices in untreated HIV infection and to evaluate their relationship with markers of immune activation and disease progression. MATERIALS AND METHODS: One hundred and eighty-five antiretroviral therapy (ART)-naïve HIV-infected and 145 HIV-negative healthy individuals were recruited. Platelet indices measured using the ADVIA 2120 platform consisted of platelet count (PLT ×10(9) /L), mean platelet volume (MPV fL), platelet distribution width (PDW%) and plateletcrit (PCT%). These were correlated with CD4 count, %CD38 on CD8+ (CD38/8) T cells, viral load, fibrinogen, D-dimers and CD31+ platelet CD62P and CD36 expression, determined using flow cytometry. RESULTS: The HIV group had decreased MPV levels [median 7.7 (7.1-8.3) vs. control group 8.4 (7.8-9.2), P < 0.0001], which correlated with PCT% (r = 0.3038, P = 0.0013), viral load (r = 0.2680, P = 0.0177) and PDW% (r = 0.2479, P = 0.0257). Additionally, the MPV correlated with CD4 count r = -0.2898, P = 0.0075. The HIV group had decreased PDW%, 49.35 (46.40-52.65) vs. control group, 53.90 (50-56.80), P = 0.0170. In addition, the PDW% showed correlations with D-dimers (r = 0.443, P = 0.03) and %CD36 (r = -0.3666, P = 0.0463). CONCLUSION: Platelet indices may offer a rapid and affordable method for monitoring platelet activation and disease progression in patients with HIV.