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Antimycobacterial immune responses in HIV-infected children starting antiretroviral therapy in Lusaka, Zambia
Abstract
Background: Children infected with HIV are at risk of developing tuberculosis (TB). Antiretroviral therapy has been linked to improved immune responses to TB. The objectives of the study were to determine the magnitude and quality of immune reconstitution in HIV-infected children receiving antiretroviral therapy (ART) and to determine pathogen-specific immune reconstitution to Mycobacterium tuberculosis.
Methods: A total of 59 children of age 9 months to 5 years initiating ART with a history of BCG vaccination from Matero Reference Clinic in Lusaka were enrolled in a prospective cohort study. Demographic and clinical data were collected using questionnaires. Blood samples were drawn before starting ART, at 3 months and 6 months for measurement of T cell subsets and PPD stimulation for intracellular cytokine staining.
Results: After 6 months of ART, the median CD4 T cell percentage increased from 9.4% at baseline to 25.9% (p < 0.001). Total CD8 T cell percentage decreased from 42.8% pre-ART to 36.5% after 6 months of ART (p = 0.010). However, naïve CD8 T cells increased within the same period (p = 0.038). Both activated CD4 and CD8 T cells decreased after 6 months of ART (p < 0.001). On the other hand, both central memory CD4 and CD8 T cells increased after 6 months of ART (p = 0.029 and 0.021, respectively), while effector memory CD8 T cells decreased (p=0.006). After 3 months of ART, CD4 T cells expressing IFN-ã decreased (p = 0.033) but after 6 months of ART the percentage increased to pre-ART levels.
Conclusion: ART has a positive impact on HIV infected children, likely reducing the risk of tuberculosis as evidenced by the increases in CD4 T cells critical to an effective immune response against TB. Before starting ART, anti-mycobacterial immune responses seem to be primarily driven by effector memory T cells while after ART by central memory T cells. Therefore, central memory T cells appear to be the primary cells in restoring specific immune responses. These findings have valuable implications for TB vaccine development strategies in HIV-infected children.
Methods: A total of 59 children of age 9 months to 5 years initiating ART with a history of BCG vaccination from Matero Reference Clinic in Lusaka were enrolled in a prospective cohort study. Demographic and clinical data were collected using questionnaires. Blood samples were drawn before starting ART, at 3 months and 6 months for measurement of T cell subsets and PPD stimulation for intracellular cytokine staining.
Results: After 6 months of ART, the median CD4 T cell percentage increased from 9.4% at baseline to 25.9% (p < 0.001). Total CD8 T cell percentage decreased from 42.8% pre-ART to 36.5% after 6 months of ART (p = 0.010). However, naïve CD8 T cells increased within the same period (p = 0.038). Both activated CD4 and CD8 T cells decreased after 6 months of ART (p < 0.001). On the other hand, both central memory CD4 and CD8 T cells increased after 6 months of ART (p = 0.029 and 0.021, respectively), while effector memory CD8 T cells decreased (p=0.006). After 3 months of ART, CD4 T cells expressing IFN-ã decreased (p = 0.033) but after 6 months of ART the percentage increased to pre-ART levels.
Conclusion: ART has a positive impact on HIV infected children, likely reducing the risk of tuberculosis as evidenced by the increases in CD4 T cells critical to an effective immune response against TB. Before starting ART, anti-mycobacterial immune responses seem to be primarily driven by effector memory T cells while after ART by central memory T cells. Therefore, central memory T cells appear to be the primary cells in restoring specific immune responses. These findings have valuable implications for TB vaccine development strategies in HIV-infected children.
