Plasma Cytokine Levels in Tanzanian HIV-1-Infected Adults and the Effect of Antiretroviral Treatment

Objective: To evaluate the role immune activation leading to the production and circulation of cytokines has in the pathogenesis of HIV infection in sub-Saharan Africa and the effect of antiretroviral treatment (ART) on these parameters. Methods: Plasma concentrations of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, IL-8, monocyte chemotactic protein (MCP)-1, IL-10, and IL-1 receptor antagonist; plasma HIV RNA; hemoglobin concentration; and white blood cells were measured in 229 HIV-infected, 54 HIV-uninfected, and after 2 and 4 months, respectively, of ART in 35 eligible individuals in northeastern Tanzania. Results: Plasma levels of tumor necrosis factor-alpha, IL-6, IL-8, monocyte chemotactic protein-1, and IL-1 receptor antagonist were significantly higher in HIV-infected individuals compared with HIV-uninfected individuals and also significantly higher in HIV-infected individuals with CD4 cell counts below 200 cells per microliter than individuals with CD4 cell counts above 200 cells per microliter. HIV RNA was the strongest predictor of all cytokine expression in multivariate analysis. ART leads to a decrease in all cytokines to levels close to those of HIV-uninfected individuals. Conclusions: Our findings support the role of HIV viral replication as the most important promoter of immune activation and prove the importance of ART in reducing immune activation and viral replication even in sub-Saharan Africa where patients are-exposed to an abundance of other infectious agents.