Differential effects of antiretrovirals on microbial translocation and gut microbiota composition of HIV-infected patients
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Study information
-
Quality control
- Retracted paper
- Contamination issues suspected
- Batch effect issues suspected
- Uncontrolled confounding suspected
- Results are suspect (various reasons)
- Tags applied
study design
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
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
Reviewed Marked as Reviewed by Svetlana up on 2025-1-20
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
- Feces Cow dung,Cow pat,Droppings,Dung,Excrement,Excreta,Faeces,Fecal material,Fecal matter,Fewmet,Frass,Guano,Matières fécales@fr,Merde@fr,Ordure,Partie de la merde@fr,Piece of shit,Porción de mierda@es,Portion of dung,Portion of excrement,Portion of faeces,Portion of fecal material,Portion of fecal matter,Portion of feces,Portion of guano,Portion of scat,Portionem cacas,Scat,Spoor,Spraint,Stool,Teil der fäkalien@de,Feces,feces
- 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 (Control)
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- HIV-positive (naive)
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- This group includes untreated HIV-infected patients (HIV+(naive)) with an average viral load of 54,010 cop/mL (3,550–71,800 cop/mL))
- 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
- 5
- Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
- 3 months
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).
- relative abundances
- Statistical test
- Kruskall-Wallis
- 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, body mass index, sex
Alpha Diversity
- Chao1 Abundance-based estimator of species richness
- decreased
- Richness Number of species
- decreased
Signature 1
Signature 2
Reviewed Marked as Reviewed by Svetlana up on 2025-1-20
Source: Table 2
Description: The relative abundance of major phyla in the gut in HIV-positive (naive).
Abundance in Group 1: decreased abundance in HIV-positive (naive)
| NCBI | Quality Control | Links |
|---|---|---|
| Alphaproteobacteria |
Revision editor(s): Joiejoie, KateRasheed
Experiment 2
Reviewed Marked as Reviewed by Svetlana up on 2025-1-20
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- non-infected volunteers (Control)
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- HIV-positive (cART)
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- This group includes HIV-infected patients on cART (HIV+(cART)) for at least one year and with viral load of <20 cop/mL.
- Group 1 sample size Number of subjects in the case (exposed) group
- 45
Lab analysis
Statistical Analysis
Signature 1
Reviewed Marked as Reviewed by Svetlana up on 2025-1-20
Source: Table 2
Description: Relative abundance of major phyla present in the gut in HIV-positive (cART).
Abundance in Group 1: increased abundance in HIV-positive (cART)
| NCBI | Quality Control | Links |
|---|---|---|
| Deltaproteobacteria | ||
| Pseudomonadota | ||
| Lentisphaerota | ||
| Synergistota |
Revision editor(s): Joiejoie, KateRasheed
Signature 2
Reviewed Marked as Reviewed by Svetlana up on 2025-1-20
Source: Table 2
Description: Relative abundance of major phyla present in the gut in HIV-positive (cART).
Abundance in Group 1: decreased abundance in HIV-positive (cART)
| NCBI | Quality Control | Links |
|---|---|---|
| Methanobacteriota |
Revision editor(s): Joiejoie, KateRasheed
Experiment 3
Reviewed Marked as Reviewed by Svetlana up on 2025-1-20
Differences from previous experiment shown
Subjects
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- NRTIs + PIs
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- This group includes patients on family treatment of nucleoside reverse transcriptase inhibitors (NRTIs) and protease inhibitors (PIs)
- Group 1 sample size Number of subjects in the case (exposed) group
- 15
Lab analysis
Statistical Analysis
Alpha Diversity
- Chao1 Abundance-based estimator of species richness
- decreased
- Richness Number of species
- decreased
Signature 1
Signature 2
Reviewed Marked as Reviewed by Svetlana up on 2025-1-20
Source: In-text result of "Gut microbiota diversity and composition"
Description: Relative abundance of major phyla present in the gut in NRTIs + PIs.
Abundance in Group 1: decreased abundance in NRTIs + PIs
| NCBI | Quality Control | Links |
|---|---|---|
| Bacillota |
Revision editor(s): Joiejoie, KateRasheed
Experiment 4
Reviewed Marked as Reviewed by Svetlana up on 2025-1-20
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- NRTIs + PIs
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- NRTIs + NNRTIs
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- This group includes patients on family treatment of nucleoside reverse transcriptase inhibitors (NRTIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs)
- Group 0 sample size Number of subjects in the control (unexposed) group
- 15
- Group 1 sample size Number of subjects in the case (exposed) group
- 22
Lab analysis
Statistical Analysis
- Matched on Factors on which subjects have been matched on in a case-control study
- Not specified
Alpha Diversity
- Chao1 Abundance-based estimator of species richness
- increased
- Richness Number of species
- increased
Signature 1
Reviewed Marked as Reviewed by Svetlana up on 2025-1-20
Source: Table 2
Description: Relative abundance of major phyla present in the gut in NRTIs + INSTIs.
Abundance in Group 1: increased abundance in NRTIs + NNRTIs
| NCBI | Quality Control | Links |
|---|---|---|
| Deltaproteobacteria |
Revision editor(s): Joiejoie, KateRasheed
Experiment 5
Reviewed Marked as Reviewed by Svetlana up on 2025-1-20
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- NRTIs + NNRTIs
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- NRTIs + INSTIs
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- This group includes patients on family treatment of nucleoside reverse transcriptase inhibitors (NRTIs) with integrase strand transfer inhibitors (INSTIs)
- Group 0 sample size Number of subjects in the control (unexposed) group
- 22
- Group 1 sample size Number of subjects in the case (exposed) group
- 8
Lab analysis
Statistical Analysis
Alpha Diversity
- Chao1 Abundance-based estimator of species richness
- increased
- Richness Number of species
- increased
Signature 1
Reviewed Marked as Reviewed by Svetlana up on 2025-1-20
Source: Table 2
Description: Relative abundance of major phyla present in the gut in NRTIs + INSTIs.
Abundance in Group 1: increased abundance in NRTIs + INSTIs
| NCBI | Quality Control | Links |
|---|---|---|
| Alphaproteobacteria |
Revision editor(s): Joiejoie, KateRasheed
Experiment 6
Reviewed Marked as Reviewed by Svetlana up on 2025-1-20
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- non-infected volunteers (Control)
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- NRTIs+PIs
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- This group includes patients on family treatment of nucleoside reverse transcriptase inhibitors (NRTIs) and protease inhibitors (PIs)
- 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
- 15
Lab analysis
Statistical Analysis
- Statistical test
- Mann-Whitney (Wilcoxon)
- Matched on Factors on which subjects have been matched on in a case-control study
- age, body mass index, sex
Alpha Diversity
- Chao1 Abundance-based estimator of species richness
- decreased
- Richness Number of species
- decreased
Signature 2
Reviewed Marked as Reviewed by Svetlana up on 2025-1-20
Source: Table 3
Description: Relative abundance of taxonomical groups (order, family, genus, species) in NRTIs+PIs
Abundance in Group 1: decreased abundance in NRTIs+PIs
Revision editor(s): Joiejoie, KateRasheed
Signature 3
Reviewed Marked as Reviewed by Svetlana up on 2025-1-20
Source: Table 3
Description: Relative abundance of taxonomical groups (order, family, genus, species) in NRTIs+PIs
Abundance in Group 1: increased abundance in NRTIs+PIs
| NCBI | Quality Control | Links |
|---|---|---|
| Eggerthella | ||
| Clostridiales bacterium | ||
| Lachnospiraceae | ||
| Blautia sp. 3Blautia sp. 3 | ||
| Flavonifractor plautii |
Revision editor(s): KateRasheed
Experiment 7
Reviewed Marked as Reviewed by Svetlana up on 2025-1-20
Differences from previous experiment shown
Subjects
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- NRTIs + NNRTIs
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- This group includes patients on family treatment of nucleoside reverse transcriptase inhibitors (NRTIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs)
- Group 1 sample size Number of subjects in the case (exposed) group
- 22
Lab analysis
Statistical Analysis
Alpha Diversity
- Chao1 Abundance-based estimator of species richness
- decreased
- Richness Number of species
- decreased
Signature 1
Reviewed Marked as Reviewed by Svetlana up on 2025-1-20
Source: Table 3
Description: Combined antiretroviral therapy modified the relative abundance of taxonomical groups (order, family, genus, species) in NRTIs+NNRTIs
Abundance in Group 1: increased abundance in NRTIs + NNRTIs
| NCBI | Quality Control | Links |
|---|---|---|
| Coriobacteriaceae | ||
| Coriobacteriales | ||
| Lachnospiraceae | ||
| Pseudomonas |
Revision editor(s): Joiejoie, KateRasheed
Signature 2
Reviewed Marked as Reviewed by Svetlana up on 2025-1-20
Source: Table 3
Description: Combined antiretroviral therapy modified the relative abundance of taxonomical groups (order, family, genus, species) in NRTIs+NNRTIs
Abundance in Group 1: decreased abundance in NRTIs + NNRTIs
Revision editor(s): Joiejoie, KateRasheed
Experiment 8
Reviewed Marked as Reviewed by Svetlana up on 2025-1-20
Differences from previous experiment shown
Subjects
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- NRTIs + INSTIs
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- This group includes patients on family treatment of nucleoside reverse transcriptase inhibitors (NRTIs) with integrase strand transfer inhibitors (INSTIs)
- Group 1 sample size Number of subjects in the case (exposed) group
- 8
Lab analysis
Statistical Analysis
Alpha Diversity
- Chao1 Abundance-based estimator of species richness
- decreased
- Richness Number of species
- decreased
Signature 1
Reviewed Marked as Reviewed by Svetlana up on 2025-1-20
Source: Table 3
Description: Combined antiretroviral therapy modified the relative abundance of taxonomical groups (order, family, genus, species) in NRTIs+INSTIs
Abundance in Group 1: increased abundance in NRTIs + INSTIs
| NCBI | Quality Control | Links |
|---|---|---|
| Desulfovibrionales | ||
| Selenomonadales | ||
| Lachnospiraceae | ||
| Desulfovibrionaceae | ||
| Desulfovibrio | ||
| Blautia sp. 3Blautia sp. 3 | ||
| Parabacteroides merdae |
Revision editor(s): Joiejoie
Signature 2
Reviewed Marked as Reviewed by Svetlana up on 2025-1-20
Source: Table 3
Description: Combined antiretroviral therapy modified the relative abundance of taxonomical groups (order, family, genus, species) in NRTIs+INSTIs
Abundance in Group 1: decreased abundance in NRTIs + INSTIs
Revision editor(s): Joiejoie, KateRasheed
Experiment 9
Reviewed Marked as Reviewed by Svetlana up on 2025-1-20
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Control
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- HIV non coinfected patients
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- This group includes HIV-infected patients who are not coinfected with other infections such as hepatitis B virus (HBV) or hepatitis C virus (HCV).
- Group 1 sample size Number of subjects in the case (exposed) group
- 25
Lab analysis
Statistical Analysis
Signature 2
Reviewed Marked as Reviewed by Svetlana up on 2025-1-20
Source: Supplementary Table 1
Description: Relative abundance of major phyla present in the gut in non-coinfected HIV patients
Abundance in Group 1: decreased abundance in HIV non coinfected patients
| NCBI | Quality Control | Links |
|---|---|---|
| Gammaproteobacteria |
Revision editor(s): Joiejoie, KateRasheed
Experiment 10
Reviewed Marked as Reviewed by Svetlana up on 2025-1-20
Differences from previous experiment shown
Subjects
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- HIV coinfected patients
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- This group includes HIV-infected patients who are also coinfected with either hepatitis B virus (HBV) or hepatitis C virus (HCV).
Lab analysis
Statistical Analysis
Alpha Diversity
- Chao1 Abundance-based estimator of species richness
- decreased
- Richness Number of species
- decreased
Signature 1
Reviewed Marked as Reviewed by Svetlana up on 2025-1-20
Source: Supplementary Table 1
Description: Relative abundance of major phyla present in the gut in coinfected patients.
Abundance in Group 1: increased abundance in HIV coinfected patients
| NCBI | Quality Control | Links |
|---|---|---|
| Actinomycetota | ||
| Deltaproteobacteria | ||
| Pseudomonadota |
Revision editor(s): Joiejoie, KateRasheed
Experiment 11
Reviewed Marked as Reviewed by Svetlana up on 2025-1-20
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Non-coinfected
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- coinfected patients
- Group 0 sample size Number of subjects in the control (unexposed) group
- 25
Lab analysis
Statistical Analysis
Alpha Diversity
- Chao1 Abundance-based estimator of species richness
- unchanged
- Richness Number of species
- unchanged
Signature 1
Reviewed Marked as Reviewed by Svetlana up on 2025-1-20
Source: Supplementary Table 2, Supplementary Table 1
Description: Abundance of lower taxonomic levels (genus and species) which were significantly increased in feces from coinfected patients
Abundance in Group 1: increased abundance in coinfected patients
| NCBI | Quality Control | Links |
|---|---|---|
| Bacteroides | ||
| Parabacteroides | ||
| Parabacteroides merdae | ||
| Gammaproteobacteria | ||
| Actinomycetota |
Revision editor(s): Joiejoie, KateRasheed
Signature 2
Reviewed Marked as Reviewed by Svetlana up on 2025-1-20
Source: Supplementary Table 2
Description: Abundance of lower taxonomic levels (genus and species) which were significantly decreased in feces from coinfected patients
Abundance in Group 1: decreased abundance in coinfected patients
| NCBI | Quality Control | Links |
|---|---|---|
| Clostridium | ||
| Coriobacterium | ||
| Pseudomonas | ||
| Roseburia | ||
| Roseburia inulinivorans | ||
| Ruminococcus | ||
| Sinorhizobium sp. |
Revision editor(s): Joiejoie, KateRasheed
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