Effects of antiretroviral therapy on immune function of HIV-infected adults with pulmonary tuberculosis and CD4+ >350 cells/mm3

Abstract

Background: Human immunodeficiency virus (HIV)-tuberculosis coinfection is associated with heightened immune activation, viral replication, and T cell dysfunction. We compared changes in T cell activation and function between patients receiving concurrent treatment for HIV-tuberculosis coinfection and those receiving treatment for tuberculosis alone.

Methods: HIV-infected adults with tuberculosis and CD4(+) T cell counts >350 cells/mm(3) were randomized to receive tuberculosis treatment alone (control arm; n = 36) or 6 months of antiretroviral therapy (ART) concurrent with tuberculosis treatment (intervention arm; n = 38). HIV viral load, T cell subsets, T cell activation, and cytokine production were measured at enrollment and every 3 months for 12 months.

Results: Differences in absolute CD4(+) and CD8(+) T cell counts were not observed between arms. Viral load was reduced while participants received ART; control patients maintained viral load at baseline levels. Both arms had significant reductions in T cell expression of CD38 and HLA-DR. Interferon-γ production in response to mitogen increased significantly in the intervention arm.

Conclusions: In HIV-infected adults with tuberculosis and CD4(+) T cell counts >350 cells/mm(3), both tuberculosis treatment and concurrent HIV-tuberculosis treatment reduce T cell activation and stabilize T cell counts. Concurrent ART with tuberculosis treatment does not provide additional, sustained reductions in T cell activation among individuals with preserved immunologic function.

Figure 1.

Changes in median human immunodeficiency virus (HIV) viral load, CD4⁺, and CD8⁺ T cell counts among participants receiving tuberculosis treatment alone (A,C) and combined HIV-tuberculosis treatment (B,D). Median values ± interquartile range are shown (A,B). Boxes indicate the interquartile ranges, the horizontal lines transecting the boxes indicate the medians, and the whiskers indicate the highest and lowest values (C,D). Nonparametric rank tests were performed to compare median changes in viral load, CD4⁺, and CD8⁺ T cell counts within each treatment arm from baseline to months 3, 6, 9, and 12. Significant P values are indicated. TB, tuberculosis.

Figure 2.

Changes in CD8⁺ T cell activation markers in response to tuberculosis treatment alone and combined human immunodeficiency virus (HIV)–tuberculosis treatment. Percentage expression of CD38 and CD38/HLA-DR on CD8⁺ T cells at baseline and 3, 6, 9, and 12 months was measured for participants receiving tuberculosis treatment alone (A,C) and combined HIV-tuberculosis treatment (B,D). The boxes indicate the interquartile ranges, the horizontal lines transecting the boxes indicate the medians, and the whiskers indicate the highest and lowest values. Nonparametric rank tests were performed to compare median changes in percentage of CD38⁺ and CD38⁺/HLA-DR⁺ CD8⁺ T cells within each treatment group from baseline to months 3, 6, 9, and 12. Significant P values are indicated. TB, tuberculosis.

Figure 3.

Changes in CD4⁺ T cell activation markers in response to tuberculosis treatment alone and combined human immunodeficiency virus (HIV)–tuberculosis treatment. Percentage expression of CD38 and CD38/HLA-DR on CD4⁺ T cells at baseline and at 3, 6, 9, and 12 months was measured among participants receiving tuberculosis treatment alone (A,C) and combined HIV-tuberculosis treatment (B,D). The boxes indicate the interquartile ranges, the horizontal lines transecting the boxes indicate the medians, and the whiskers indicate the highest and lowest values. Nonparametric rank tests were performed to compare median changes in percentage of CD38⁺ and CD38⁺/HLA-DR⁺ CD4⁺ T cells within each treatment group from baseline to months 3, 6, 9, and 12. Significant P values are indicated. TB, tuberculosis.

Figure 4.

Changes in whole-blood IFN-γ production in response to phytohemagglutinin (PHA), M. tuberculosis culture filtrate, M. tuberculosis antigen 85B, p24 protein/ human immunodeficiency virus (HIV) clade A, and p24 protein/HIV clade D in response to tuberculosis treatment alone (A,C) and to combined HIV-tuberculosis treatment (B,D). Median values ± standard deviations are shown. Nonparametric rank tests were performed to compare median changes in IFN-γ production within each treatment group from baseline to months 3, 6, 9, and 12. Significant P values are indicated.