Abstract

Introduction:In response to the human immunodeficiency virus (HIV) infection, activated immune cells produce several cytokines that alter the immune response and HIV disease progression. We quantified Th1/Th2/Th17 cytokines in an antiretroviral therapy naïve (ART) cohort to investigate their correlation with traditional markers of HIV disease progression; CD4+ T-lymphocytes and virus load (VL).Methods:We enrolled 247 HIV-infected ART-naïve participants into the study. CD4+ T- and CD8+ T-lymphocytes were enumerated using flow cytometry. VL was quantified using the Cavidi ExaVirTMLoad assay. IL-2, IL-4, IL-6, IL-10, IL-17A, TNF-α, and IFN-γ levels were quantified using the BD Cytometric Bead Array Human Th1/Th2/Th17 cytokine assay. The Kendall’s rank correlation coefficient was used to determine the correlation between log10transformed data for cytokine levels and CD4+ T- and CD8+ T-lymphocytes, CD4/CD8 ratio, and VL.Results:The median CD4+ T- and CD8+ T-lymphocyte counts were 458 cells/µL (IQR:405-556) and 776 cells/µL (IQR:581-1064), respectively. The median CD4/CD8 ratio was 0.6 (IQR: 0.45-0.86). The median VL was log103.3.copies/mL (IQR:2.74-3.93). Low CD4+ T-lymphocyte counts (p=0.010) and CD4/CD8 ratio (p=0.044) were significantly correlated with high VL. There was no significant correlation of cytokine levels with CD4+ T-, CD8+ T-lymphocyte counts and CD4/CD8 ratio. However, high levels of IL-17A (p=0.012) and IL-6 (p=0.034) were significantly correlated with high VL.Conclusion:Our study contributes to the little knowledge available on the role of cytokine profiles in the immune response to subtype C HIV infection.

Highlights

  • In response to the human immunodeficiency virus (HIV) infection, activated immune cells produce several cytokines that alter the immune response and HIV disease progression

  • It is well established that whilst there is a depletion of CD4+ Tlymphocytes counts in HIV infection, there is a compensatory increase in CD8+T-lymphocyte leading to a reduced CD4/CD8 ratio which is normally greater than 1 [16]

  • In a previous study [17] we showed that the CD4/CD8 ratio could be used as a potential tool for diagnosis of HIV infection in infants under the age of 18 months and in adults

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Summary

Introduction

In response to the human immunodeficiency virus (HIV) infection, activated immune cells produce several cytokines that alter the immune response and HIV disease progression. We quantified Th1/Th2/Th17 cytokines in an antiretroviral therapy naïve (ART) cohort to investigate their correlation with traditional markers of HIV disease progression; CD4+ T-lymphocytes and virus load (VL). Cytokines are crucial to cellular communication and may be key elements in turning on and off the immune response [1]. They play a critical role in immune system homeostasis. There is an intense cytokine “storm” during acute HIV infection [2] which might contribute to severe immune activation, rapid CD4+ T-lymphocyte depletion and increase in virus replication leading to high virus load. Other cytokines; Transforming Growth Factor (TGF)-β, IL-10, IL-13, and IL-4 have been shown to have both activating and inhibitory roles on HIV replication [7]

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