Mycobacterium tuberculosis co-infection is associated with increased surrogate marker of the HIV reservoir

Abstract

Background: Tuberculosis (Tb) is the most frequent opportunistic infection among people living with HIV infection. The impact of Tb co-infection in the establishment and maintenance of the HIV reservoir is unclear.

Method: We enrolled 13 HIV-infected patients with microbiologically confirmed Tb and 10 matched mono-HIV infected controls. Total HIV DNA in peripheral blood mononuclear cells (PBMCs), plasma interleukin-7 (IL-7) concentrations and the activities of indoleamine 2,3-dioxygenase (IDO) were measured for all the participants prior to therapy and after antiretroviral therapy (ART).

Results: After a duration of 16 (12, 22) months' ART, patients co-infected with Tb who were cured of Tb maintained higher levels of HIV DNA compared with mono-HIV infected patients [2.89 (2.65- 3.05) log₁₀ copies/10⁶ cells vs. 2.30 (2.11-2.84) log₁₀ copies/10⁶ cells, P = 0.008]. The levels of on-ART HIV DNA were positively correlated with the baseline viral load (r = 0.64, P = 0.02) in Tb co-infected group. However, neither plasma IL-7 concentration nor plasma IDO activity was correlated with the level of on-ART HIV DNA.

Conclusions: Tb co-infection was associated with the increased surrogate marker of the HIV reservoir, while its mechanism warrants further examination.

Keywords: 3-dioxygenas; HIV; Indoleamine 2; Interleukin-7; Reservoir; Tuberculosis.

Fig. 1

The levels of HIV DNA differ between mono-HIV infected patients and HIV/Tb co-infected patients. a The levels of HIV DNA in the mono-HIV infected group and HIV/Tb co-infected group at baseline. b, c Change in the level of HIV DNA in each group after more than 1year’s ART. d The levels of HIV DNA in the mono-HIV infected group and HIV/Tb co-infected group after ART. All the data analyzed by non-parametric test

Fig. 2

Correlations between the levels of on-ART HIV DNA and factors (baseline viral load, on-ART CD4 cell count and on-ART CD4/CD8 ratio). The correlation analyzed between the levels of on-ART HIV DNA and baseline viral load (a), on-ART CD4 cell count (b), and on-ART CD4/CD8 ratio (c) in mono-HIV infected group. Similarly, the correlation analyzed between the levels of on-ART HIV DNA and baseline viral load (d), on-ART CD4 cell count (e), and on-ART CD4/CD8 ratio (f) in HIV/Tb co-infected group. All the data analyzed by non-parametric test. The blue dot represents mono-HIV infected patients and the orange dot represents HIV/Tb co-infected patients

Fig. 3

Correlations of plasma IL-7 concentrations with the levels of on-ART HIV DNA. The plasma IL-7 concentrations in the two groups group at baseline (a), and after ART (b). The correlations between the levels of on-ART HIV DNA and the plasma IL-7 concentrations both at baseline and after ART in the mono-HIV infected group and HIV/Tb co-infected group, respectively (c−f). All the data analyzed by non-parametric test. The blue dot represents mono-HIV infected patients and the orange dot represents HIV/Tb co-infected patients

Fig. 4

Correlations of plasma IDO activities with the levels of on-ART HIV DNA. The plasma IDO activities in the two groups at baseline (a), and after ART (b). The correlations between the levels of on-ART HIV DNA and the plasma IDO activities both at baseline and after ART in the mono-HIV infected group and HIV/Tb co-infected group, respectively (c–f). All the data analyzed by non-parametric test. The blue dot represents mono-HIV infected patients and the orange dot represents HIV/Tb co-infected patients