Rectal Microbiome Alterations Associated With Oral Human Immunodeficiency Virus Pre-Exposure Prophylaxis

Study information

Needs review

study design

cross-sectional observational, not case-control

Citation

PMID PubMed identifier for scientific articles.

32258202

DOI Digital object identifier for electronic documents.

10.1093/ofid/ofz463

URI

Authors

Fulcher JA, Li F, Cook RR, Zabih S, Louie A, Okochi H, Tobin NH, Gandhi M, Shoptaw S, Gorbach PM, Aldrovandi GM

Journal

Open forum infectious diseases

Year

2019

Keywords:

men who have sex with men (MSM), pre-exposure prophylaxis (PrEP), rectal microbiome

Background: Oral daily tenofovir (TFV) disoproxil fumarate/emtricitabine (TDF/FTC) for human immunodeficiency virus (HIV) pre-exposure prophylaxis (PrEP) is highly effective for HIVprevention, yet long-term effects are not fully understood. We investigated the effects of PrEP on the rectal microbiome in a cohort of men who have sex with men (MSM). Methods: This cross-sectional analysis included HIV-negative MSM either on PrEP (n = 37) or not (n = 37) selected from an ongoing cohort using propensity score matching. Rectal swabs were used to examine microbiome composition using 16S ribosomal ribonucleic acid gene sequencing, and associations between PrEP use and microbiota abundance were examined. Hair specimens were used to quantify TFV and FTC exposure over the past 6 weeks on a subset of participants (n = 15). Results: Pre-exposure prophylaxis use was associated with a significant increase in Streptococcus abundance (adjusted P = .015). Similar associations were identified using least absolute shrinkage and selection operator (LASSO) regression, confirming the increase in Streptococcus and also showing increased Mitsuokella, Fusobacterium, and decreased Escherichia/Shigella. Increased Fusobacterium was significantly associated with increasing TFV exposure. Conclusions: Oral TDF/FTC for PrEP is associated with rectal microbiome changes compared to well matched controls, specifically increased Streptococcus and Fusobacterium abundance. This study highlights the need for future investigations of the role of microbiome changes on HIV susceptibility and effectiveness of PrEP.

Experiment 1

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Curated date: 2021/01/10

Curator: WikiWorks

Revision editor(s): LGeistlinger, WikiWorks

Subjects

Location of subjects: United States of America

Host species Species from which microbiome was sampled (if applicable): Homo sapiens

Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology: Rectum Intestinum rectum,Rectal sac,Terminal portion of intestine,Terminal portion of large intestine,Rectum

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology: HIV/AIDS pre-exposure prophylaxis AIDS pre-exposure prophylaxis,HIV pre-exposure prophylaxis,HIV/AIDS pre-exposure prophylaxis

Group 0 name Corresponds to the control (unexposed) group for case-control studies: HIV-negative MSM not on PrEP
Group 1 name Corresponds to the case (exposed) group for case-control studies: HIV-negative MSM on PrEP
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: HIV-negative Men who have sex with men (MSM) on HIV pre-exposure prophylaxis (PrEP)
Group 0 sample size Number of subjects in the control (unexposed) group: 37
Group 1 sample size Number of subjects in the case (exposed) group: 37

Lab analysis

Sequencing type: 16S

16S variable region One or more hypervariable region(s) of the bacterial 16S gene: V4

Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance: Illumina

Statistical Analysis

Statistical test: LASSO regression Statistical test: "LASSO regression" is not in the list (ANCOM, ANOSIM, ANOVA, DESeq2, edgeR, Fisher's Exact Test, Kruskall-Wallis, LEfSe, Linear Regression, Logistic Regression, ...) of allowed values.

Significance threshold p-value or FDR threshold used for differential abundance testing (if any): 0.1
MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?: Yes
Matched on Factors on which subjects have been matched on in a case-control study: age, ethnic group, nicotine dependence, obesity, anal intercourse, marijuana, race, Matched on: "methamphetaime dependence" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.methamphetaime dependence, Matched on: "alcohol consumption" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.alcohol consumption

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness: unchanged
Chao1 Abundance-based estimator of species richness: unchanged
Simpson Estimator of species richness and species evenness: more weight on species evenness: unchanged
Richness Number of species: unchanged

Signature 1

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Curated date: 2021/01/10

Curator: Michael Lutete

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Source: Figure 1, Figure 2, Text

Description: Pre-exposure prophylaxis use associates with differential abundance of specific bacterial genera

Abundance in Group 1: increased abundance in HIV-negative MSM on PrEP

NCBI	Quality Control	Links
Streptococcus
Fusobacterium
Mitsuokella

Revision editor(s): WikiWorks

Signature 2

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Source: Figure 1, Figure 2, Text

Description: Pre-exposure prophylaxis use associates with differential abundance of specific bacterial genera

Abundance in Group 1: decreased abundance in HIV-negative MSM on PrEP

NCBI	Quality Control	Links
Escherichia
Shigella

Revision editor(s): WikiWorks

Experiment 2

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Curated date: 2021/01/10

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Differences from previous experiment shown

Subjects

Lab analysis

Statistical Analysis

Statistical test: Zero-inflated negative binomial regression Statistical test: "Zero-inflated negative binomial regression" is not in the list (ANCOM, ANOSIM, ANOVA, DESeq2, edgeR, Fisher's Exact Test, Kruskall-Wallis, LEfSe, Linear Regression, Logistic Regression, ...) of allowed values.

Significance threshold p-value or FDR threshold used for differential abundance testing (if any): 0.05

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness: unchanged
Chao1 Abundance-based estimator of species richness: unchanged
Simpson Estimator of species richness and species evenness: more weight on species evenness: unchanged
Richness Number of species: unchanged