Differential effects of antiretroviral treatment on immunity and gut microbiome composition in people living with HIV in rural versus urban Zimbabwe
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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
Burkhart Colorado AS, Lazzaro A, Neff CP, Nusbacher N, Boyd K, Fiorillo S, Martin C, Siebert JC, Campbell TB, Borok M, Palmer BE, Lozupone C
Journal
Microbiome
Year
2024
Keywords:
ART response, HIV, Immune activation and exhaustion, Inflammation, Intestinal microbiome, Rural, Urban
BACKGROUND: The widespread availability of antiretroviral therapy (ART) has dramatically reduced mortality and improved life expectancy for people living with HIV (PLWH). However, even with HIV-1 suppression, chronic immune activation and elevated inflammation persist and have been linked to a pro-inflammatory gut microbiome composition and compromised intestinal barrier integrity. PLWH in urban versus rural areas of sub-Saharan Africa experience differences in environmental factors that may impact the gut microbiome and immune system, in response to ART, yet this has not previously been investigated in these groups. To address this, we measured T cell activation/exhaustion/trafficking markers, plasma inflammatory markers, and fecal microbiome composition in PLWH and healthy participants recruited from an urban clinic in the city of Harare, Zimbabwe, and a district hospital that services surrounding rural villages. PLWH were either ART naïve at baseline and sampled again after 24 weeks of first-line ART and the antibiotic cotrimoxazole or were ART-experienced at both timepoints. RESULTS: Although expected reductions in the inflammatory marker IL-6, T-cell activation, and exhaustion were observed with ART-induced viral suppression, these changes were much more pronounced in the urban versus the rural area. Gut microbiome composition was the most highly altered from healthy controls in ART experienced PLWH, and characterized by both reduced alpha diversity and altered composition. However, gut microbiome composition showed a pronounced relationship with T cell activation and exhaustion in ART-naïve PLWH, suggesting a particularly significant role for the gut microbiome in disease progression in uncontrolled infection. Elevated immune exhaustion after 24 weeks of ART did correlate with both living in the rural location and a more Prevotella-rich/Bacteroides-poor microbiome type, suggesting a potential role for rural-associated microbiome differences or their co-variates in the muted improvements in immune exhaustion in the rural area. CONCLUSION: Successful ART was less effective at reducing gut microbiome-associated inflammation and T cell activation in PLWH in rural versus urban Zimbabwe, suggesting that individuals on ART in rural areas of Zimbabwe may be more vulnerable to co-morbidity related to sustained immune dysfunction in treated infection. Video Abstract.
Experiment 1
Reviewed Marked as Reviewed by Svetlana up on 2024-7-15
Curated date: 2024/03/08
Curator: Nwajei Edgar
Revision editor(s): Nwajei Edgar, Scholastica, Keamy, Victoria
Subjects
- Location of subjects
- Zimbabwe
- 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
- Gut microbiome measurement Gut microbiome measurement,gut microbiome measurement
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Healthy controls (HC)
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Antiretroviral therapy (ART) Naïve at baseline
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- PLWH (people living with HIV) who were not on ART at the first timepoint but who subsequently commenced first-line ART with efavirenz/lamivudine/tenofovir disoproxil fumarate (EFV/3TC/TDF) and the prophylactic antibiotic cotrimoxazole (ART Naïve) - Baseline
- Group 0 sample size Number of subjects in the control (unexposed) group
- 42
- Group 1 sample size Number of subjects in the case (exposed) group
- 67
- Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
- Use of antibiotics (apart from co-trimoxazole) within 2 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).
- centered log-ratio
- Statistical test
- ANCOM
- 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
- Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
- Confounders controlled for: "location" 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.location, Confounders controlled for: "viral load" 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.viral load
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- decreased
Signature 1
Reviewed Marked as Reviewed by Svetlana up on 2024-7-15
Source: Figure 4A
Description: Differential abundance of genera in ART-naïve compared to HC using ANCOM-BC, significant differential log-fold changes between microbes were calculated relative to healthy controls using only baseline values.
Abundance in Group 1: decreased abundance in Antiretroviral therapy (ART) Naïve at baseline
| NCBI | Quality Control | Links |
|---|---|---|
| Clostridium |
Revision editor(s): Nwajei Edgar, Ayibatari, Keamy
Experiment 2
Reviewed Marked as Reviewed by Svetlana up on 2024-7-15
Curated date: 2024/03/13
Curator: Nwajei Edgar
Revision editor(s): Nwajei Edgar, Scholastica, Keamy, Victoria
Differences from previous experiment shown
Subjects
- Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
- Clinical treatment Clinical treatment,clinical treatment
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Antiretroviral therapy (ART) naïve at baseline and after 24 weeks of first-line ART
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- PLWH (people living with HIV) who were not on antiretroviral therapy (ART) at the first timepoint but who subsequently commenced first-line ART with efavirenz/lamivudine/tenofovir disoproxil fumarate (EFV/3TC/TDF) and the prophylactic antibiotic cotrimoxazole (ART Naïve) - two time points.
- Group 1 sample size Number of subjects in the case (exposed) group
- 52
Lab analysis
Statistical Analysis
- Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
- time, Confounders controlled for: "viral load" 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.viral load, Confounders controlled for: "location" 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.location
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- decreased
Signature 2
Reviewed Marked as Reviewed by Svetlana up on 2024-7-15
Source: Figure 4B
Description: ART-naïve compared to HC with Model using two time points.
Abundance in Group 1: decreased abundance in Antiretroviral therapy (ART) naïve at baseline and after 24 weeks of first-line ART
| NCBI | Quality Control | Links |
|---|---|---|
| Blastocystis | ||
| Butyrivibrio | ||
| Turicibacter | ||
| Clostridium |
Revision editor(s): Nwajei Edgar, Ayibatari, Keamy
Experiment 3
Reviewed Marked as Reviewed by Svetlana up on 2024-7-15
Differences from previous experiment shown
Subjects
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Antiretroviral therapy (ART) experienced at baseline
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- PLWH (people living with HIV) who were on ART regimen and cotrimoxazole at baseline
- Group 1 sample size Number of subjects in the case (exposed) group
- 33
Lab analysis
Statistical Analysis
- Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
- Confounders controlled for: "location" 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.location, Confounders controlled for: "viral load" 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.viral load
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- decreased
Signature 1
Reviewed Marked as Reviewed by Svetlana up on 2024-7-15
Source: Figure 4A
Description: Differential abundance of genera in ART experienced compared to HC using ANCOM-BC, significant differential log-fold changes between microbes were calculated relative to healthy controls using only baseline values.
Abundance in Group 1: increased abundance in Antiretroviral therapy (ART) experienced at baseline
| NCBI | Quality Control | Links |
|---|---|---|
| Megamonas | ||
| Lachnoclostridium |
Revision editor(s): Keamy
Signature 2
Reviewed Marked as Reviewed by Svetlana up on 2024-7-15
Source: Figure 4A
Description: Differential abundance of genera in ART experienced compared to HC using ANCOM-BC, significant differential log-fold changes between microbes were calculated relative to healthy controls using only baseline values.
Abundance in Group 1: decreased abundance in Antiretroviral therapy (ART) experienced at baseline
| NCBI | Quality Control | Links |
|---|---|---|
| Blastocystis | ||
| Butyrivibrio | ||
| Turicibacter | ||
| Clostridium |
Revision editor(s): Keamy
Experiment 4
Reviewed Marked as Reviewed by Svetlana up on 2024-7-15
Differences from previous experiment shown
Subjects
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Antiretroviral therapy (ART) experienced at baseline and after 24 weeks
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- PLWH (people living with HIV) who were on ART regimen and cotrimoxazole at both time points
- Group 1 sample size Number of subjects in the case (exposed) group
- Not specified
Lab analysis
Statistical Analysis
- Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
- time, Confounders controlled for: "location" 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.location, Confounders controlled for: "viral load" 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.viral load
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- decreased
Signature 1
Reviewed Marked as Reviewed by Svetlana up on 2024-7-15
Source: 4B
Description: Differential abundance of genera in ART experienced compared to HC using ANCOM-BC, significant differential log-fold changes between microbes were calculated relative to healthy controls using both time points.
Abundance in Group 1: increased abundance in Antiretroviral therapy (ART) experienced at baseline and after 24 weeks
| NCBI | Quality Control | Links |
|---|---|---|
| Megamonas | ||
| Lachnoclostridium | ||
| Bilophila |
Revision editor(s): Keamy
Signature 2
Reviewed Marked as Reviewed by Svetlana up on 2024-7-15
Source: 4B
Description: Differential abundance of genera in ART experienced compared to HC using ANCOM-BC, significant differential log-fold changes between microbes were calculated relative to healthy controls using both time points.
Abundance in Group 1: decreased abundance in Antiretroviral therapy (ART) experienced at baseline and after 24 weeks
| NCBI | Quality Control | Links |
|---|---|---|
| Blastocystis | ||
| Butyrivibrio | ||
| Turicibacter | ||
| clostridia UCG-014clostridia UCG-014 | ||
| Clostridium |
Revision editor(s): Keamy
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