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.
To explore early biomarkers for establishing more sensitive safety evaluation assays in preclinical settings that determine the potential risks during the application of microbicide candidates, three representative microbicide candidates (cellulose sulphate, nonoxynol-9 and tenofovir), whose safety profiles have been well established in clinical trials, were included to gauge the sensitivities of different assays. Both mouse models and cell lines were employed to determine the sensitivities. The recruitment of immune cells at topical mucosal sites and the upregulation of HIV receptor/coreceptors in vitro were identified as highly sensitive biomarkers of the impact of microbicide candidates. Our data suggest that different evaluations/assays have their inherent sensitivities, and at least one assay from each sensitivity level should be included in the safety evaluation algorithm.
The main heroine traffic from Yunnan province to the Xinjiang Autonomous Region is believed to initiate the transmission of CRF07_BC which is the predominant strain in intravenous drug users (IDUs) in China. However, the great distances between Yunnan and Xinjiang lead to an unclear and elusive diffusion process of CRF07_BC due to the absence of an important middle site such as Sichuan province. Moreover, in recent years the rapidly increasing infection rate among IDUs in the Liangshan region of Sichuan made it necessary to characterize the genetic character of the circulating strain of Sichuan IDUs. In this study, we characterized the genetic character of seven newly isolated CRF07_BC genomes (five from Sichuan and two from Xinjiang) and analyzed the transmission linkage among strains from IDUs in different regions. By conducting Markov chain Monte Carlo (MCMC) analysis and reconstruction of neighbor-joining trees and maximum-likelihood trees, our results revealed the genetic variation and important role of Sichuan-derived CRF07_BC strains during the transmission of CRF07_BC.
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