The effects of highly active antiretroviral therapy on the serum levels of pro-inflammatory and anti-inflammatory cytokines in HIV infected subjects

Background: Cytokines play an important role in controlling the homeostasis of the immune system and infection with Human Immunodeficiency virus (HIV) leads to deregulated production of both pro- and anti-inflammatory cytokines. This study was designed to determine the effects of HIV and Highly Active Antiretroviral Therapy (HAART) on the levels of pro-and anti-inflammatory cytokines in HIV infected subjects.

Method: A total of 50 HIV infected and 50 HIV seronegative control participants were recruited for the study. The HIV infected subjects were recruited before commencement of antiretroviral therapy and were followed up for 12 months. Blood samples were collected at 3 different points: before initiation of therapy, 6 months into therapy and 12 months into therapy. Serum cytokines were analyzed using ELISA method while CD4+ T cells and viral load counts were measured using standard laboratory methods.

Result: The results showed that pro-inflammatory cytokines: Tumour necrosis factor-alpha (TNF-α), Interleukin-6 (IL-6) and anti-inflammatory cytokines Interleukin-4 (IL-4), Interleukin-10 (IL-10) and Transforming growth factor-beta (TGF-β) were significantly elevated in HIV infected subjects before commencement of therapy compared to 6 months and 12 months into therapy (P < 0.01) and compared to control participants (P < 0.01). TNF-α, TGF-beta remained significantly elevated even after 12 months of therapy compared to control participants (P < 0.01), while IL-4, IL-6, and IL-10 showed no significant difference compared to control participants after 12 months of therapy (P > 0.05). INF-γ was significantly reduced before commencement of therapy and after 12 months of therapy compared to control participants (P < 0.05) respectively.

Conclusion: TNF-α and TGF-β remained significantly elevated even after 12 months of therapy, while IFN-γ remained significantly reduced after 12 months of therapy. Regulating these cytokines which were unresponsive to therapy could serve as a potential measure of therapy for HIV infected subjects. The positive effect of 12 months therapy on IL-4, IL-6 and IL-10 levels can be used to monitor disease prognosis during therapy especially in resource poor setting where regular viral load monitoring is unavailable.