Monocyte activation and dysregulation in treated and untreated hiv-1 infected Ugandans.
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Introduction: Mechanism for increased non-AIDs co morbidities in HIV-1infected individuals on combinatorial antiretroviral therapy (cART) still requires exploration. This is majorly attributed to chronic monocyte activation and inflammation that persist regardless of effective HIV-1 therapy . Monocytes mediate inflammation and so are crucial in development of non-AIDS co morbidities like cardiovascular disease (CVD) [7-9]. More explorative efforts are still needed to understand the mechanisms underlying monocyte related immune activation in these individuals here in Uganda. In this study, we investigated monocyte subsets, their phenotypic and functional variations as predictors of non- AIDs related illnesses amongst treated HIV-I infected Ugandans. Methods; This was a nested cross sectional study. Using flow cytometry, we determined and compared; i) subsets variation (using HLA-DR, CD14 and CD16 expression) ii) activation phenotypes using CD163, CD80 and PDL-1 expression and iii) intracellular cytokine(IL-10,IL-6 and TNF-α) production of monocyte subsets in PBMC samples of treated HIV-1 infected individuals. Results; HAART naïve HIV-Infected individuals showed increased percentages with statistical significance of nonclassical (CD14+CD16++) monocyte subsets (p=0.0264). Both intermediate and classical subsets were increased but showed no statistical significance. HAART naïve HIV-1 infected individuals also showed increased phenotypic marker (CD163,CD80,PDL-1) expression in both non-classical CD14+CD16++ (p=0.03, p=0.0234, p=0.0234) and intermediate CD14++CD16+ (p=0.0156, p=0.0163, p=0.0156) monocyte subsets, with reduction in expression for classical subsets (p=0.1484, p>0.999) respectively. The mean percentages of cytokines IL10 and TNF-α produced were increased with statistical significance in non-classical CD14+CD16++ (p=0.8438, p=0.00391), intermediate CD14++CD16+ (p=0.250, p=0.0068) and classical CD14++CD16- (p=0.0078, p=0.0 156) subsets in HAART naïve individuals in comparison to HAART treated individuals. On the contrary, IL-6 produced by non-classical subsets showed no significance for both HIV-1 infected groups (p=0.1094).