Mycobacterium tuberculosis co-infection is associated with increased surrogate marker of the HIV reservoir
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AIDS Research and Therapy Open Access
RESEARCH
Mycobacterium tuberculosis co‑infection is associated with increased surrogate marker of the HIV reservoir Jingna Xun1†, Tangkai Qi2†, Lei Zou2,3†, Qi Tang1, Yinzhong Shen2, Junyang Yang2, Luman Xie4, Yongjia Ji2, Renfang Zhang2, Li Liu2, Jiangrong Wang2, Corky Steinhart5,6, Zhenyan Wang2, Yang Tang2, Wei Song2, Jianjun Sun2, Juan Cheng3, Xiaoqin Le2, Huanmei Wu2, Xiaoqing He2, Rong Chen2, Jun Chen2*† and Hongzhou Lu2,7*†
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: HIV, Tuberculosis, Reservoir, Interleukin-7, Indoleamine 2, 3-dioxygenas Background Currently, there are 36.9 million people living with HIV (PWH), including approximately 1.8 million new cases of infection each year [1]. Antiretroviral therapy (ART) substantially decreases the mortality of HIV-infected *Correspondence: [email protected]; [email protected] † Jingna Xun, Tangkai Qi and Lei Zou contributed equally to this manuscript. † Jun Chen and Hongzhou Lu contributed equally to this manuscript. 2 Department of Infection and Immunity, Shanghai Public Health Clinical Center, Fudan University, 2901 Caolang Road, Shanghai 201508, China Full list of author information is available at the end of the article
patients and improves the quality of life of PWH [2, 3]. The main barrier in eradicating HIV infection is the presence of the HIV reservoir [4], which refers to the persistence of replication-competent provirus among PWH undergoing long-term effective ART [5]. The mainly site for the HIV reservoir is normally referred to CD4 + T cells, dendritic cells (DCs), and macrophages [6]. Chomont et al. estimated that the half-life of HIV latent cells was 39.5 months, and it was speculated that 65.7 years of effective ART would be needed to remove 1 million cells with latent HI
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