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Characterization of the Intestinal Fungal Microbiome in HIV and HCV Mono-Infected or Co-Infected Patients.

ABSTRACT: Intestinal mycobiome dysbiosis plays an important role in the advancement of HIV- and HCV-infected patients. Co-infection with HCV is an important risk factor for exacerbating immune activation in HIV-infected patients, and gut fungal microbial dysbiosis plays an important role. However, no systematic study has been conducted on the intestinal fungal microbiome of HIV/HCV co-infected patients to date. Patients infected with HIV and HCV, either alone or in combination, and healthy volunteers were included. Stool samples were collected for fungal ITS sequencing and for further mycobiome statistical analysis. We found that the abundance of fungal species significantly decreased in the HIV/HCV co-infection group compared to in the healthy control group, while no significant differences were found in the mono-infection groups. Low-CD4 + T-cell patients in the HIV group and high-ALT-level patients in the HCV group were discovered to have a more chaotic fungal community. Furthermore, the opportunistic pathogenic fungal profiles and fungal inter-correlations in the co-infection group became less characteristic but more complicated than those in the mono-infection groups. Intestinal fungal dysregulation occurs in HIV- and HCV-infected patients, and this dysregulation is further complicated in HIV/HCV co-infected patients.

SUBMITTER: Yin Y

PROVIDER: S-EPMC9412373 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature

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Characterization of the Intestinal Fungal Microbiome in HIV and HCV Mono-Infected or Co-Infected Patients.

Yin Yue Y Tuohutaerbieke Maermaer M Feng Chengjie C Li Xinjie X Zhang Yuqi Y Xu Qiang Q Tu Jing J Yang Ence E Zou Qinghua Q Shen Tao T

Viruses 20220818 8

Intestinal mycobiome dysbiosis plays an important role in the advancement of HIV- and HCV-infected patients. Co-infection with HCV is an important risk factor for exacerbating immune activation in HIV-infected patients, and gut fungal microbial dysbiosis plays an important role. However, no systematic study has been conducted on the intestinal fungal microbiome of HIV/HCV co-infected patients to date. Patients infected with HIV and HCV, either alone or in combination, and healthy volunteers were ...[more]

PMID: 36016433

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Project description:BackgroundImmune biomarkers are implicated in HCV treatment response, fibrosis, and accelerated pathogenesis of comorbidities, though only D-dimer and C-reactive protein have been consistently studied. Few studies have evaluated HIV/HCV co-infection, and little longitudinal data exists describing a broader antiviral cytokine response.MethodsFifty immune biomarkers were analyzed at baseline (BL) and HCV end of treatment follow-up(FU) time point using the Luminex 50-plex assay in plasma samples from 15 HCV-cleared, 24 HCV mono- and 49 HIV/HCV co-infected patients receiving antiretroviral treatment, who either did or did not receive pegylated-interferon/ribavirin HCV treatment. Biomarker levels were compared among spontaneous clearance patients, mono- and co-infected, untreated and HCV-treated, and sustained virologic responders (SVR) and non-responders (NR) at BL and FU using nonparametric analyses. A Bonferroni correction, adjusting for tests of 50 biomarkers, was used to reduce Type I error.ResultsCompared to HCV patients at BL, HIV/HCV patients had 22 significantly higher and 4 significantly lower biomarker levels, following correction for multiple testing. There were no significantly different BL levels when comparing SVR and NR in mono- or co-infected patients; however, FU levels changed considerably in co-infected patients, with seven becoming significantly higher and eight becoming significantly lower in SVR patients. Longitudinally between BL and FU, 13 markers significantly changed in co-infected SVR patients, while none significantly changed in co-infected NR patients. There were also no significant changes in longitudinal analyses of mono-infected patients achieving SVR or mono-infected and co-infected groups deferring treatment.ConclusionsClear differences exist in pattern and quantity of plasma immune biomarkers among HCV mono-infected, HIV/HCV co-infected, and HCV-cleared patients; and with SVR in co-infected patients treated for HCV. Though >90% of patients were male and co-infected had a larger percentage of African American patients, our findings may have implications for better understanding HCV pathogenesis, treatment outcomes, and future therapeutic targets.

Project description:BackgroundApproximately 180 million people worldwide, (3 % of the world's population) are infected with hepatitis C (HCV). Insulin resistance (IR) and type 2 diabetes (T2DM) are common extrahepatic manifestations of chronic HCV infection and associated with poor treatment and liver-related outcomes. The presence of these metabolic complications have been associated with poor response to interferon-based HCV antiviral therapy and increased risk of liver-related outcomes. Metformin, an insulin sensitizer is known to improve HCV treatment response and has been associated with a reduced risk of developing hepatocellular carcinoma (HCC). This study will evaluate the effect of metformin on preventing progression or promoting regression of liver fibrosis, rate of virologic cure (SVR) and other metabolic measures in HCV-HIV co-infected and HCV mono-infected study participants who have IR and are planning on initiating HCV treatment.MethodsThis study is a prospective 48-week single-centre, randomized, open-label, controlled trial of HIV-HCV co-infected and HCV mono-infected patients with IR (HOMA-IR ≥ 2.0) who are planning to initiate HCV antiviral therapy. Sixty participants will be recruited from The Ottawa Hospital Viral Hepatitis Clinic. Participants will be randomized in a 1:1 ratio to either arm 1, metformin 2 g (1 g twice daily) plus lifestyle, or to arm 2, lifestyle alone. The primary outcome will be the change in FibroScan® score (kPa) from baseline to week 12 (start of HCV treatment), the end of HCV treatment (week 24) and 24 weeks post HCV treatment (week 48). Secondary outcomes include changes in liver fibrosis using AST to platelet ratio index, changes in glucose and lipid levels, anthropometric measures, changes in alpha-fetoprotein levels, patient acceptability, and changes in dietary and physical activity parameters.DiscussionThis pilot study will be the first to evaluate the role of metformin on liver fibrosis in HCV-HIV co-infected and HCV mono-infected patients with IR receiving DAA HCV treatment. If metformin is effective in reducing liver fibrosis in this patient population, this will represent a well-tolerated, easy-to-administer, inexpensive therapy that will protect against negative HCV outcomes. This study will also be an opportunity to evaluate the impact of insulin resistance and hyperglycemia on viral clearance in HCV-infected patients treated with interferon-free regimens.Trial registrationClinicalTrials.gov NCT02306070 version 4.0 (June 29, 2015).

Dataset Information

Characterization of the Intestinal Fungal Microbiome in HIV and HCV Mono-Infected or Co-Infected Patients.

Publications

Characterization of the Intestinal Fungal Microbiome in HIV and HCV Mono-Infected or Co-Infected Patients.

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