Dataset Information

Exploring the interplay between antiretroviral therapy and the gut-oral microbiome axis in people living with HIV.

ABSTRACT: The gut and oral microbiome is altered in people living with HIV (PLWH). While antiretroviral treatment (ART) is pivotal in restoring immune function in PLWH, several studies have identified an association between specific antiretrovirals, particularly integrase inhibitors (INSTI), and weight gain. In our study, we explored the differences in the oral and gut microbiota of PLWH under different ART regimens, and its correlation to Body Mass Index (BMI). Fecal and salivary samples were collected from PLWH (n = 69) and healthy controls (HC, n = 80). We performed taxonomy analysis to determine the microbial composition and relationship between microbial abundance and ART regimens, BMI, CD4+T-cell count, CD4/CD8 ratio, and ART duration. PLWH showed significantly lower richness compared to HC in both the oral and gut environment. The gut microbiome composition of INSTI-treated individuals was enriched with Faecalibacterium and Bifidobacterium, whereas non-nucleotide reverse transcriptase inhibitor (NNRTI)-treated individuals were enriched with Gordonibacter, Megasphaera, and Staphylococcus. In the oral microenvironment, Veillonella was significantly more abundant in INSTI-treated individuals and Fusobacterium and Alloprevotella in the NNRTI-treated individuals. Furthermore, Bifidobacterium and Dorea were enriched in gut milieu of PLWH with high BMI. Collectively, our findings identify distinct microbial profiles, which are associated with different ART regimens and BMI in PLWH on successful ART, thereby highlighting significant effects of specific antiretrovirals on the microbiome.

SUBMITTER: Narayanan A

PROVIDER: S-EPMC11294597 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Exploring the interplay between antiretroviral therapy and the gut-oral microbiome axis in people living with HIV.

Narayanan Aswathy A Kieri Oscar O Vesterbacka Jan J Manoharan Lokeshwaran L Chen Puran P Ghorbani Mahin M Ljunggren Hans-Gustaf HG Sällberg Chen Margaret M Aleman Soo S Sönnerborg Anders A Ray Shilpa S Nowak Piotr P

Scientific reports 20240801 1

The gut and oral microbiome is altered in people living with HIV (PLWH). While antiretroviral treatment (ART) is pivotal in restoring immune function in PLWH, several studies have identified an association between specific antiretrovirals, particularly integrase inhibitors (INSTI), and weight gain. In our study, we explored the differences in the oral and gut microbiota of PLWH under different ART regimens, and its correlation to Body Mass Index (BMI). Fecal and salivary samples were collected f ...[more]

PMID: 39090139

Similar Datasets

Project description:BackgroundThe 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.ResultsAlthough 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.ConclusionSuccessful 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.

Project description:IntroductionSince the evolution of highly active antiretroviral therapy (ART), a near-perfect ART adherence level (>95%) is needed to control viral suppression. Non-adherence to treatment may lead to acquired immunodeficiency syndrome (AIDS) and drug resistance. Though the Bangladesh government provides free treatment and counselling services to people living with human immunodeficiency virus (PLHIV), only 22% of the identified PLHIV continue treatment. Therefore, this study aims to explore the barriers that obstruct the Bangladeshi PLHIV to ensure ART adherence.MethodsWe conducted a qualitative study in Dhaka, Bangladesh, and recruited the sensitive study population following non-probability, mainly purposive sampling from a community-based registered organization for PLHIV. We conducted the in-depth interview using a semi-structured guideline with 15 consented respondents. We transcribed the audio-recorded interviews in the local language (Bangla) and then translated those into English for data analysis. During the data extraction process, the lead and corresponding authors independently extracted raw data to generate different themes and sub-themes and invited other authors to contribute when they could not solve any discrepancies.ResultsThe study identified three significant categories of barriers at the individual, community, and institutional levels that negatively interfered with ART adherence. The most dominant barriers were discrimination and rejection related to stigma, as almost all participants mentioned these barriers. Stigmatizing attitudes and the discriminatory act of the community people and healthcare providers critically affected their treatment adherence. Other leading barriers were improper inventory management of ART-related medicines and CD4 tests and lack of proper counselling. In addition, we found that a positive approach toward life and family support motivated some respondents to overcome the barriers.ConclusionsWe recommended strengthening Bangladesh's HIV/AIDS prevention, treatment, and management program with a special focus on the improvement of the supply chain of ART-related medicines and CD4 tests and ensuring proper counselling. In addition, we recommended strengthening the behaviour change communication and IEC activities at a large scale to destigmatize health facilities and community levels.

Project description:BackgroundDespite antiretroviral therapy (ART) being widely available, HIV continues to cause substantial illness and premature death in low-and-middle-income countries. High rates of loss to follow-up after HIV diagnosis can delay people starting ART. Starting ART within seven days of HIV diagnosis (rapid ART initiation) could reduce loss to follow-up, improve virological suppression rates, and reduce mortality.ObjectivesTo assess the effects of interventions for rapid initiation of ART (defined as offering ART within seven days of HIV diagnosis) on treatment outcomes and mortality in people living with HIV. We also aimed to describe the characteristics of rapid ART interventions used in the included studies.Search methodsWe searched CENTRAL, the Cochrane Database of Systematic Reviews, MEDLINE, Embase, and four other databases up to 14 August 2018. There was no restriction on date, language, or publication status. We also searched ClinicalTrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform, and websites for unpublished literature, including conference abstracts.Selection criteriaWe included randomized controlled trials (RCTs) that compared rapid ART versus standard care in people living with HIV. Children, adults, and adolescents from any setting were eligible for inclusion.Data collection and analysisTwo review authors independently assessed the eligibility of the studies identified in the search, assessed the risk of bias and extracted data. The primary outcomes were mortality and virological suppression at 12 months. We have presented all outcomes using risk ratios (RR), with 95% confidence intervals (CIs). Where appropriate, we pooled the results in meta-analysis. We assessed the certainty of the evidence using the GRADE approach.Main resultsWe included seven studies with 18,011 participants in the review. All studies were carried out in low- and middle-income countries in adults aged 18 years old or older. Only one study included pregnant women.In all the studies, the rapid ART intervention was offered as part of a package that included several cointerventions targeting individuals, health workers and health system processes delivered alongside rapid ART that aimed to facilitate uptake and adherence to ART.Comparing rapid ART with standard initiation probably results in greater viral suppression at 12 months (RR 1.18, 95% CI 1.10 to 1.27; 2719 participants, 4 studies; moderate-certainty evidence) and better ART uptake at 12 months (RR 1.09, 95% CI 1.06 to 1.12; 3713 participants, 4 studies; moderate-certainty evidence), and may improve retention in care at 12 months (RR 1.22, 95% CI 1.11 to 1.35; 5001 participants, 6 studies; low-certainty evidence). Rapid ART initiation was associated with a lower mortality estimate, however the CIs included no effect when compared to standard of care (RR 0.72, 95% CI 0.51 to 1.01; 5451 participants, 7 studies; very low-certainty evidence). It is uncertain whether rapid ART has an effect on modification of ART treatment regimens as data are lacking (RR 7.89, 95% CI 0.76 to 81.74; 977 participants, 2 studies; very low-certainty evidence). There was insufficient evidence to draw conclusions on the occurrence of adverse events.Authors' conclusionsRCTs that include initiation of ART within one week of diagnosis appear to improve outcomes across the HIV treatment cascade in low- and middle-income settings. The studies demonstrating these effects delivered rapid ART combined with several setting-specific cointerventions. This highlights the need for pragmatic research to identify feasible packages that assure the effects seen in the trials when delivered through complex health systems.

Project description:Alterations in the gut microbiome are associated with neurocognition and related disorders, including in the context of human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infection. However, the connection between the gut microbiome and cognitive decline, gauged by increased dependence in instrumental activities of daily living (IADL), remains largely unexplored in the context of these diseases. Here we characterized the gut microbiome using 16S rRNA amplicon sequencing and untargeted metabolomics with liquid chromatography-mass spectrometry from 347 people with HIV, HIV and HCV, or neither, all of whom underwent a comprehensive neuropsychiatric assessment. We observed that IADL-dependent and -independent HIV-monoinfected (HIV-positive [HIV+]/HCV-negative [HCV-]) and coinfected (HIV+/HCV+) individuals have distinct gut microbiomes. Moreover, we found that dependent individuals with HIV or HIV and HCV were enriched in Bacteroides These results may have implications for the characterization of cognitive decline, as well as the development of potential prevention and treatment strategies for individuals infected with HIV and/or HCV. Of particular interest is the possibility that dietary interventions that are known to modify the microbiome could be used to shift the microbiome toward more favorable states for preserving independence.IMPORTANCE The microbes in the gut and the chemicals they produce by metabolism have been linked to brain function. In earlier work, we showed that infection with two viruses, HIV and HCV, changed the gut microbes and metabolism in ways that were associated with a lifetime history of major depressive disorder. Here, we extend this analysis looking at a measurement of independence in daily living. We find that in individuals with HIV, whether or not they also have HCV, those who reported reduced independence were enriched in a genus of bacteria called Bacteroides This result is interesting because Bacteroides is strongly associated with diets low in carbohydrates and high in animal protein, suggesting that diet changes may help preserve independent living in people living long-term with HIV (although clinical intervention trials would be needed in order to confirm this).

Dataset Information

Exploring the interplay between antiretroviral therapy and the gut-oral microbiome axis in people living with HIV.

Publications

Exploring the interplay between antiretroviral therapy and the gut-oral microbiome axis in people living with HIV.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets