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4117 UNIQUE VAGINAL MICROBIOME POPULATIONS AND MICROBIAL GENE CONTENT AMONG WOMEN WHO NATURALLY CONTROL HIV PROGRESSION

OBJECTIVES/GOALS: The role of the vaginal microbiome (VM) in HIV disease progression is poorly understood. We examined VMs of HIV+ Elite Controllers (ECs) and HIV+ Long-Term Non-Progressors (LTNPs) compared to controls: HIV-positive antiretroviral (ARV) treated (HIV+ATs) and HIV-negative women in th...

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Autores principales: Michel, Katherine Gisella, Ma, Bing, Weber, Kathleen, McClellan, Leah, Sheth, Anandi, Gange, Stephen, French, Audrey, Ravel, Jacques, Ofotokun, Igho, Merenstein, Daniel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cambridge University Press 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8823142/
http://dx.doi.org/10.1017/cts.2020.102
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author Michel, Katherine Gisella
Ma, Bing
Weber, Kathleen
McClellan, Leah
Sheth, Anandi
Gange, Stephen
French, Audrey
Ravel, Jacques
Ofotokun, Igho
Merenstein, Daniel
author_facet Michel, Katherine Gisella
Ma, Bing
Weber, Kathleen
McClellan, Leah
Sheth, Anandi
Gange, Stephen
French, Audrey
Ravel, Jacques
Ofotokun, Igho
Merenstein, Daniel
author_sort Michel, Katherine Gisella
collection PubMed
description OBJECTIVES/GOALS: The role of the vaginal microbiome (VM) in HIV disease progression is poorly understood. We examined VMs of HIV+ Elite Controllers (ECs) and HIV+ Long-Term Non-Progressors (LTNPs) compared to controls: HIV-positive antiretroviral (ARV) treated (HIV+ATs) and HIV-negative women in the Women’s Interagency HIV Study (DC/Chicago/Atlanta sites). METHODS/STUDY POPULATION: VMs were surveyed via both V3/V4 region of 16S rRNA gene amplicon sequencing and metagenomics sequencing in 67 women across 4 study groups: 1) LTNPs (CD4 >500 cells/mL for 5+ years without ARVs) (n = 7) and 2) ECs (HIV RNA <80 copies/mL for 2+ years without ARVs) (n = 8), matched with 3) HIV+ ATs (on ARVs for ≥1 year with CD4 increase ≥100 cells/mm(3)) (n = 34), and 4) HIV- women (n = 18). Metagenomes were characterized from specimens collected at two time points: 1) vaginal swabs collected 2016-2017 (n = 62) and 2) cervicovaginal lavage collected 2002-2016 (n = 35; DC/Chicago only). We used VIRGO (human vaginal non-redundant gene catalog), a newly developed referencing framework to comprehensively catalog VM gene content, taxonomy and functions. RESULTS/ANTICIPATED RESULTS: Women were 89% African American with a mean age of 46 years (SD 8.8). The most prevalent species were Gardnerella vaginalis (predominant in 34%), Lactobacillus iners (predominant in 21%), and L. crispatus (predominant in 14%). 90% of LTNP and 45% of EC samples were Lactobacillus-dominant vs. 28% of HIV- and 30% of HIV+ATs. L. crispatus and L. iners in ECs/LTNPs had significantly different gene content and greater gene richness vs. controls. G. vaginalis-predominant communities were found in 66% of HIV- and 68% of HIV+ATs, compared to 46% of EC and 0% of LTNP. The G. vaginalis strains present in EC/LTNP also showed significantly lower gene richness and different gene content vs. controls. DISCUSSION/SIGNIFICANCE OF IMPACT: These results suggest unique VM communities among EC/LTNP, and led us to hypothesize that differential regulation of vaginal immunity drives the observed differences. The similarity between VMs of HIV- and HIV+ATs warrants further study. Larger longitudinal VM studies are needed to assess associated functional pathways and understand the etiology of VM association with HIV progression. CONFLICT OF INTEREST DESCRIPTION: The authors have no conflicts of interest to disclose.
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spelling pubmed-88231422022-02-18 4117 UNIQUE VAGINAL MICROBIOME POPULATIONS AND MICROBIAL GENE CONTENT AMONG WOMEN WHO NATURALLY CONTROL HIV PROGRESSION Michel, Katherine Gisella Ma, Bing Weber, Kathleen McClellan, Leah Sheth, Anandi Gange, Stephen French, Audrey Ravel, Jacques Ofotokun, Igho Merenstein, Daniel J Clin Transl Sci Basic Science/Methodology OBJECTIVES/GOALS: The role of the vaginal microbiome (VM) in HIV disease progression is poorly understood. We examined VMs of HIV+ Elite Controllers (ECs) and HIV+ Long-Term Non-Progressors (LTNPs) compared to controls: HIV-positive antiretroviral (ARV) treated (HIV+ATs) and HIV-negative women in the Women’s Interagency HIV Study (DC/Chicago/Atlanta sites). METHODS/STUDY POPULATION: VMs were surveyed via both V3/V4 region of 16S rRNA gene amplicon sequencing and metagenomics sequencing in 67 women across 4 study groups: 1) LTNPs (CD4 >500 cells/mL for 5+ years without ARVs) (n = 7) and 2) ECs (HIV RNA <80 copies/mL for 2+ years without ARVs) (n = 8), matched with 3) HIV+ ATs (on ARVs for ≥1 year with CD4 increase ≥100 cells/mm(3)) (n = 34), and 4) HIV- women (n = 18). Metagenomes were characterized from specimens collected at two time points: 1) vaginal swabs collected 2016-2017 (n = 62) and 2) cervicovaginal lavage collected 2002-2016 (n = 35; DC/Chicago only). We used VIRGO (human vaginal non-redundant gene catalog), a newly developed referencing framework to comprehensively catalog VM gene content, taxonomy and functions. RESULTS/ANTICIPATED RESULTS: Women were 89% African American with a mean age of 46 years (SD 8.8). The most prevalent species were Gardnerella vaginalis (predominant in 34%), Lactobacillus iners (predominant in 21%), and L. crispatus (predominant in 14%). 90% of LTNP and 45% of EC samples were Lactobacillus-dominant vs. 28% of HIV- and 30% of HIV+ATs. L. crispatus and L. iners in ECs/LTNPs had significantly different gene content and greater gene richness vs. controls. G. vaginalis-predominant communities were found in 66% of HIV- and 68% of HIV+ATs, compared to 46% of EC and 0% of LTNP. The G. vaginalis strains present in EC/LTNP also showed significantly lower gene richness and different gene content vs. controls. DISCUSSION/SIGNIFICANCE OF IMPACT: These results suggest unique VM communities among EC/LTNP, and led us to hypothesize that differential regulation of vaginal immunity drives the observed differences. The similarity between VMs of HIV- and HIV+ATs warrants further study. Larger longitudinal VM studies are needed to assess associated functional pathways and understand the etiology of VM association with HIV progression. CONFLICT OF INTEREST DESCRIPTION: The authors have no conflicts of interest to disclose. Cambridge University Press 2020-07-29 /pmc/articles/PMC8823142/ http://dx.doi.org/10.1017/cts.2020.102 Text en © The Association for Clinical and Translational Science 2020 https://creativecommons.org/licenses/by/4.0/This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Basic Science/Methodology
Michel, Katherine Gisella
Ma, Bing
Weber, Kathleen
McClellan, Leah
Sheth, Anandi
Gange, Stephen
French, Audrey
Ravel, Jacques
Ofotokun, Igho
Merenstein, Daniel
4117 UNIQUE VAGINAL MICROBIOME POPULATIONS AND MICROBIAL GENE CONTENT AMONG WOMEN WHO NATURALLY CONTROL HIV PROGRESSION
title 4117 UNIQUE VAGINAL MICROBIOME POPULATIONS AND MICROBIAL GENE CONTENT AMONG WOMEN WHO NATURALLY CONTROL HIV PROGRESSION
title_full 4117 UNIQUE VAGINAL MICROBIOME POPULATIONS AND MICROBIAL GENE CONTENT AMONG WOMEN WHO NATURALLY CONTROL HIV PROGRESSION
title_fullStr 4117 UNIQUE VAGINAL MICROBIOME POPULATIONS AND MICROBIAL GENE CONTENT AMONG WOMEN WHO NATURALLY CONTROL HIV PROGRESSION
title_full_unstemmed 4117 UNIQUE VAGINAL MICROBIOME POPULATIONS AND MICROBIAL GENE CONTENT AMONG WOMEN WHO NATURALLY CONTROL HIV PROGRESSION
title_short 4117 UNIQUE VAGINAL MICROBIOME POPULATIONS AND MICROBIAL GENE CONTENT AMONG WOMEN WHO NATURALLY CONTROL HIV PROGRESSION
title_sort 4117 unique vaginal microbiome populations and microbial gene content among women who naturally control hiv progression
topic Basic Science/Methodology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8823142/
http://dx.doi.org/10.1017/cts.2020.102
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