Differential effects of antiretrovirals on microbial translocation and gut microbiota composition of HIV-infected patients

Study information

Needs review

study design

cross-sectional observational, not case-control

Citation

PMID PubMed identifier for scientific articles.

28362071

DOI Digital object identifier for electronic documents.

https://doi.org/10.7448/IAS.20.1.21526

URI

Authors

Villanueva-Millán MJ, Pérez-Matute P, Recio-Fernández E, Lezana Rosales JM, Oteo JA

Journal

Journal of the International AIDS Society

Year

2017

Keywords:

HIV infection, antiretroviral therapy, bacterial diversity, gut microbiota, inflammation, microbial translocation

INTRODUCTION: Increased bacterial translocation and alterations to gut microbiota composition have been described in HIV infection and contribute to immune activation and inflammation. These effects persist despite combined antiretroviral therapy (cART). However, the contribution of different cART combinations has not yet been investigated. The aim of this study was to analyse the long-term effects of different combinations of cART on bacterial translocation and gut microbiota composition in HIV-infected patients. METHODS: We carried out a cross-sectional study of 45 HIV-infected patients on cART, classified as nucleoside reverse transcriptase inhibitors (NRTIs)+ protease inhibitors (PIs) (n = 15), NRTIs+ non-nucleoside reverse transcriptase inhibitors (NNRTIs) (n = 22), and NRTIs+ integrase strand transfer inhibitors (INSTIs) (n = 8). Untreated HIV-infected patients (n = 5) and non-infected volunteers (n = 21) were also included. Soluble markers of bacterial translocation and inflammation were measured and gut microbiota composition was analysed using 16S rDNA pyrosequencing (Illumina MiSeq). RESULTS: The NRTIs+INSTIs regimen was associated with levels of systemic inflammation that were similar to uninfected controls. The reduction in faecal bacterial diversity induced by HIV infection was also restored by this regimen. HIV infection was more closely related to changes in lower taxonomic units and diversity rather than at the phylum level. The NRTIs+PIs regimen showed the highest reduction in bacterial species, whereas NRTIs+INSTIs induced a minor loss of bacterial species and a significant increase in others. CONCLUSION: Our study demonstrated that INSTI-based ART was associated with levels of systemic inflammation and microbial diversity similar to that of uninfected controls. The role of INSTIs other than raltegravir needs to be further investigated. Patients on the NRTIs+PIs regimen presented the highest reduction in bacterial species compared with other antiretrovirals and naive patients. Thus, different cART regimens are associated with diverse profiles in gut microbiota composition. Longitudinal and functional studies are needed to better understand these findings.

Experiment 1

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Curated date: 2024/10/17

Curator: Joiejoie

Revision editor(s): Joiejoie

Subjects

Location of subjects: Spain

Host species Species from which microbiome was sampled. Contact us to have more species added.: Homo sapiens

Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology: Alimentary part of gastrointestinal system GI tract,Alimentary system,Alimentary tract,Gastro-intestinal system,Gastroenterological system,Gastrointestinal (GI) tract,Gastrointestinal system,Gastrointestinal tract,Alimentary part of gastrointestinal system,alimentary part of gastrointestinal system

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology: HIV infection [X]Human immunodeficiency virus disease,[X]Human immunodeficiency virus disease (disorder),[X]Unspecified human immunodeficiency virus [HIV] disease,[X]Unspecified human immunodeficiency virus [HIV] disease (disorder),HIV - Human immunodeficiency virus infection,HIV INFECT,HIV Infection,HIV infection,HIV Infections,HIV infectious disease,HTLV III INFECT,HTLV III Infections,HTLV III LAV INFECT,HTLV III LAV Infections,HTLV WIII INFECTIONS,HTLV WIII LAV INFECTIONS,HTLV-III Infection,HTLV-III Infections,HTLV-III-LAV Infection,HTLV-III-LAV Infections,HUMAN IMMUNO VIRUS DIS,human immunodeficiency virus,Human immunodeficiency virus [HIV] disease,HUMAN IMMUNOdeficiency VIRUS [HIV] INFECTION,Human immunodeficiency virus caused disease or disorder,Human immunodeficiency virus disease,Human immunodeficiency virus disease (disorder),Human immunodeficiency virus disease or disorder,Human immunodeficiency virus infection,Human immunodeficiency virus infection (disorder),Human immunodeficiency virus infection, NOS,Human immunodeficiency virus infectious disease,human immunodeficiency virus infectious disease,Infection, HIV,Infection, HTLV-III,Infection, HTLV-III-LAV,Infections, HIV,Infections, HTLV-III,Infections, HTLV-III-LAV,LYMPHOTROPIC VIRUS TYPE III INFECTIONS HUMAN T,T LYMPHOTROPIC VIRUS TYPE III INFECT HUMAN,T Lymphotropic Virus Type III Infections, Human,T-Lymphotropic Virus Type III Infections, Human,Unspecified human immunodeficiency virus [HIV] disease (disorder),hIV infection

Group 0 name Corresponds to the control (unexposed) group for case-control studies: non-infected volunteers

Group 1 name Corresponds to the case (exposed) group for case-control studies: non-nucleoside reverse transcriptase inhibitors (NNRTIs)

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: Group 1, defined as NRTIs + non-nucleoside reverse transcriptase inhibitors (NNRTIs), consists of 22 HIV-infected patients who were on a combination of nucleoside reverse transcriptase inhibitors and non-nucleoside reverse transcriptase inhibitors as part of their antiretroviral therapy. This group was included to analyze the specific effects of this treatment regimen on microbial translocation and gut microbiota composition compared to other regimens.

Group 0 sample size Number of subjects in the control (unexposed) group: 21

Group 1 sample size Number of subjects in the case (exposed) group: 22

Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any): The exclusion criteria for antibiotics in the study "Differential effects of antiretrovirals on microbial translocation and gut microbiota composition of HIV-infected patients" specified that patients treated with antibiotics within the last 3 months were excluded from participation. This was to ensure that any potential effects of antibiotics on gut microbiota composition and microbial translocation were not confounding factors in the study's findings.

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

Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).: raw counts

Statistical test: Chi-Square; ANOVA; Mann-Whitney (Wilcoxon); Pearson Correlation

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

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, Matched on: "gender" 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.gender, body mass index

Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment: age, Confounders controlled for: "gender" 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.gender, body mass index, Confounders controlled for: "antibiotic use" 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.antibiotic use, Confounders controlled for: "other medications" 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.other medications, Confounders controlled for: "comorbid conditions" 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.comorbid conditions

Alpha Diversity

Pielou Quantifies how equal the community is numerically: decreased

Shannon Estimator of species richness and species evenness: more weight on species richness: decreased

Chao1 Abundance-based estimator of species richness: decreased

Simpson Estimator of species richness and species evenness: more weight on species evenness: decreased

Inverse Simpson Modification of Simpsons index D as 1/D to obtain high values in datasets of high diversity and vice versa: decreased

Richness Number of species: decreased

Faith Phylogenetic diversity, takes into account phylogenetic distance of all taxa identified in a sample: decreased

Signature 1

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Curated date: 2024/10/19

Curator: Joiejoie

Revision editor(s): Joiejoie

Source: Journal of the International AIDS Society

Description: The study investigates how different combinations of combined antiretroviral therapy (cART) impact bacterial translocation and gut microbiota in HIV-infected individuals. Conducted as a cross-sectional study with 45 HIV-infected patients, the research compares the effects of various cART regimens, including NRTIs combined with protease inhibitors, non-nucleoside reverse transcriptase inhibitors, and integrase strand transfer inhibitors. The findings reveal that the NRTIs + INSTIs regimen is associated with levels of systemic inflammation and microbial diversity similar to those of uninfected controls, while other regimens show varying impacts on gut microbiota composition. The study emphasizes the need for further longitudinal research to explore these relationships in depth.

Abundance in Group 1: increased abundance in non-nucleoside reverse transcriptase inhibitors (NNRTIs)

NCBI	Quality Control	Links

Revision editor(s): Joiejoie

Signature 2

Edit History Delete

Mark reviewed

Your review change was submitted

Needs review

Curated date: 2024/10/19

Curator: Joiejoie

Revision editor(s): Joiejoie

Source: Journal of the International AIDS Society

Description: The study investigates how different combinations of combined antiretroviral therapy (cART) impact bacterial translocation and gut microbiota in HIV-infected individuals. Conducted as a cross-sectional study with 45 HIV-infected patients, the research compares the effects of various cART regimens, including NRTIs combined with protease inhibitors, non-nucleoside reverse transcriptase inhibitors, and integrase strand transfer inhibitors. The findings reveal that the NRTIs + INSTIs regimen is associated with levels of systemic inflammation and microbial diversity similar to those of uninfected controls, while other regimens show varying impacts on gut microbiota composition. The study emphasizes the need for further longitudinal research to explore these relationships in depth.

Abundance in Group 1: decreased abundance in non-nucleoside reverse transcriptase inhibitors (NNRTIs)

NCBI	Quality Control	Links

Revision editor(s): Joiejoie

Signature 3

Edit History Delete

Mark reviewed

Your review change was submitted

Needs review

Curated date: 2024/10/20

Curator: Joiejoie

Revision editor(s): Joiejoie

Source: Journal of the International AIDS Society

Description: The study investigates how different combinations of combined antiretroviral therapy (cART) impact bacterial translocation and gut microbiota in HIV-infected individuals. Conducted as a cross-sectional study with 45 HIV-infected patients, the research compares the effects of various cART regimens, including NRTIs combined with protease inhibitors, non-nucleoside reverse transcriptase inhibitors, and integrase strand transfer inhibitors. The findings reveal that the NRTIs + INSTIs regimen is associated with levels of systemic inflammation and microbial diversity similar to those of uninfected controls, while other regimens show varying impacts on gut microbiota composition. The study emphasizes the need for further longitudinal research to explore these relationships in depth.

Abundance in Group 1: decreased abundance in non-nucleoside reverse transcriptase inhibitors (NNRTIs)

NCBI	Quality Control	Links

Revision editor(s): Joiejoie