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The oral microbiome and subclinical herpesvirus shedding in HIV infected men on ART

Fike, Kendal (2019) The oral microbiome and subclinical herpesvirus shedding in HIV infected men on ART. Master's Thesis, University of Pittsburgh. (Unpublished)

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Abstract

Despite undetectable plasma HIV load and CD4 counts reconstitution due to the effective Antiretroviral Therapy (ART) people living with HIV (PWH) are still at a higher risk for developing non-AIDS-associated chronic diseases, which have been linked to systemic immune activation and inflammation. Human microbiota composed of bacteria, viruses and fungi plays an important role in the induction and function of the host immune system and the symbiosis and dysbiosis of fecal and/or oral microbiome have both the local and systemic effects on the immune system. We hypothesize that oral microbiome dysbiosis of PWH leads to systemic immune activation and contributes to non-AIDS-associated chronic diseases. The objective of this study was to evaluate whether the oral microbiome of PWH on ART is associated with levels of systemic immune activation and oral herpesvirus shedding. Thirteen HIV-infected participants on ART and 11 age matched HIV-negative controls participated in this study. Two oral samples with 6-month intervals were collected from each participant. The DNA was isolated from the samples, and the 16S rRNA V4 region was amplified of the DNA by PCR followed by sequencing using Illumina MiSeq platform. The sequence data were analyzed using Qiime2 and statistical analysis was performed by Stata. The results show there were no statistically significant differences in alpha diversity and beta diversity of oral bacteria at family level between PWH on ART and negative controls at both week 0 and week 24 time points, respectively. There are also no significant correlations between alpha diversity of oral bacteria and plasma inflammatory cytokine levels generated from the previous study. However, when the data were analyzed with herpesvirus shedding, which was obtained from a previous study using the same oral samples, alpha diversity of oral bacteria was significantly decreased in participants with HHV6 shedding compared to those who had no HHV6 shedding regardless of HIV status. In addition, the beta diversity of oral bacteria is also significantly different based on HHV6 shedding status in these oral samples. The same phenomena were not observed based on EBV, CMV or HHV8 shedding status. Our results suggest there may be intricate interplays in the oral microbiome. Future studies with a larger number of participants in each group are needed to determine the role of the oral microbiome in the systemic immune activation observed in PWH on ART. Among PWH on ART, a significant public health concern exists regarding the role of oral microbiome effect on immune activation. There is an imperative need for research to lead to a better treatment strategy concerning non-AIDS chronic diseases in this population.


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Details

Item Type: University of Pittsburgh ETD
Status: Unpublished
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Fike, KendalKEF75@pitt.eduKEF75
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairChen, YueCheny@pitt.edu
Committee MemberMartinson, Jeremyjmartins@pitt.edu
Committee MemberMacatangay, Bernardmacatangaybj@upmc.edu
Date: 20 June 2019
Date Type: Publication
Defense Date: 16 April 2019
Approval Date: 20 June 2019
Submission Date: 4 April 2019
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Number of Pages: 41
Institution: University of Pittsburgh
Schools and Programs: Graduate School of Public Health > Infectious Diseases and Microbiology
Degree: MPH - Master of Public Health
Thesis Type: Master's Thesis
Refereed: Yes
Uncontrolled Keywords: oral microbiome HIV herpesvirus subshedding ART MSM
Date Deposited: 20 Jun 2019 19:47
Last Modified: 20 Jun 2019 19:47
URI: http://d-scholarship.pitt.edu/id/eprint/36244

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