Airway pepsinogen A4 identifies lung transplant recipients with microaspiration and predicts chronic lung allograft dysfunction.

BACKGROUND: Aspiration is a known risk factor for adverse outcomes post-lung transplantation. Airway bile acids are the gold-standard biomarker of aspiration; however, they are released into the duodenum and likely reflect concurrent gastrointestinal dysmotility. Previous studies investigating total airway pepsin have found conflicting results on its relationship with adverse outcomes post-lung transplantation. These studies measured total pepsin and pepsinogen in the airways. Certain pepsinogens are constitutively expressed in the lungs, while others, such as pepsinogen A4 (PGA4), are not. We sought to evaluate the utility of measuring airway PGA4 as a biomarker of aspiration and predictor of adverse outcomes in lung transplant recipients (LTRs) early post-transplant. METHODS: Expression of PGA4 was compared to other pepsinogens in lung tissue. Total pepsin and PGA4 were measured in large airway bronchial washings and compared to preexisting markers of aspiration. Two independent cohorts of LTRs were used to assess the relationship between airway PGA4 and chronic lung allograft dysfunction (CLAD). Changes to airway PGA4 after antireflux surgery were assessed in a third cohort of LTRs. RESULTS: PGA4 was expressed in healthy human stomach but not lung. Airway PGA4, but not total pepsin, was associated with aspiration. Airway PGA4 was associated with an increased risk of CLAD in two independent cohorts of LTRs. Antireflux surgery was associated with reduced airway PGA4. CONCLUSIONS: Airway PGA4 is a marker of aspiration that predicts CLAD in LTRs. Measuring PGA4 at surveillance bronchoscopies can help triage high-risk LTRs for anti-reflux surgery.

Oesophageal stasis is a risk factor for chronic lung allograft dysfunction and allograft failure in lung transplant recipients.

Background: Morbidity and mortality in lung transplant recipients are often triggered by recurrent aspiration events, potentiated by oesophageal and gastric disorders. Previous small studies have shown conflicting associations between oesophageal function and the development of chronic lung allograft dysfunction (CLAD). Herein, we sought to investigate the relationship between oesophageal motility disorders and long-term outcomes in a large retrospective cohort of lung transplant recipients. Methods: All lung transplant recipients at the Toronto Lung Transplant Program from 2012 to 2018 with available oesophageal manometry testing within the first 7 months post-transplant were included in this study. Patients were categorised according to the Chicago Classification of oesophageal disorders (v3.0). Associations between oesophageal motility disorders with the development of CLAD and allograft failure (defined as death or re-transplantation) were assessed. Results: Of 487 patients, 57 (12%) had oesophagogastric junction outflow obstruction (OGJOO) and 47 (10%) had a disorder of peristalsis (eight major, 39 minor). In a multivariable analysis, OGJOO was associated with an increased risk of CLAD (HR 1.71, 95% CI 1.15-2.55, p=0.008) and allograft failure (HR 1.69, 95% CI 1.13-2.53, p=0.01). Major disorders of peristalsis were associated with an increased risk of CLAD (HR 1.55, 95% CI 1.01-2.37, p=0.04) and allograft failure (HR 3.33, 95% CI 1.53-7.25, p=0.002). Minor disorders of peristalsis were not significantly associated with CLAD or allograft failure. Conclusion: Lung transplant recipients with oesophageal stasis characterised by OGJOO or major disorders of peristalsis were at an increased risk of adverse long-term outcomes. These findings will help with risk stratification of lung transplant recipients and personalisation of treatment for aspiration prevention.

Triaging donor lungs based on a microaspiration signature that predicts adverse recipient outcome.

BACKGROUND: Aspiration is a relative contraindication to accepting donor lungs for transplant and is currently assessed by visual inspection of the airways via bronchoscopy. However, this method is limited as it does not assess for microaspiration. Bile acids measured in large airway bronchial wash (LABW) samples have been shown to be a marker of aspiration in lung transplant recipients. Herein, we investigate the utility of measuring total bile acids (TBA) in donor LABW to predict performance of donor lungs and recipient outcomes. METHODS: TBA was measured in 605 consecutive lung donors at the Toronto Lung Transplant Program. TBA levels were compared in donor lungs deemed unsuitable for transplant, requiring further assessment on ex vivo lung perfusion (EVLP), and those suitable for direct transplantation using Mann-Whitney-U tests. Relationships between LABW TBA concentrations and recipient outcomes were evaluated using multivariable Cox-PH models and log-rank analysis. RESULTS: Donor TBA was highest in lungs deemed unsuitable for transplant and correlated with clinical assessment of aspiration. LABW TBA concentration correlated with calcium, decreased pH, and increased pro-inflammatory mediators in EVLP perfusate. TBA cut-off of 1245 nM was able to differentiate donor lungs directly declined from those suitable for direct transplantation with a 91% specificity (AUROC: 73%). High donor TBA status was associated with the increased rate of primary graft dysfunction, longer time to extubation, and shorter time to chronic lung allograft dysfunction. CONCLUSIONS: In a large retrospective cohort, we observed that donor LABW TBA was associated with suitability of donor lungs for transplant, performance of the organ on EVLP, and adverse recipient outcomes.

Lung Allograft Microbiome Association with Gastroesophageal Reflux, Inflammation, and Allograft Dysfunction.

Rationale: It remains unclear how gastroesophageal reflux disease (GERD) affects allograft microbial community composition in lung transplant recipients and its impact on lung allograft inflammation and function. Objectives: Our objective was to compare the allograft microbiota in lung transplant recipients with or without clinically diagnosed GERD in the first year after transplant and assess associations between GERD, allograft microbiota, inflammation, and acute and chronic lung allograft dysfunction (ALAD and CLAD). Methods: A total of 268 BAL samples were collected from 75 lung transplant recipients at a single transplant center every 3 months after transplant for 1 year. Ten transplant recipients from a separate transplant center provided samples before and after antireflux Nissen fundoplication surgery. Microbial community composition and density were measured using 16S ribosomal RNA gene sequencing and quantitative polymerase chain reaction, respectively, and inflammatory markers and bile acids were quantified. Measurements and Main Results: We observed a range of allograft community composition with three discernible types (labeled community state types [CSTs] 1-3). Transplant recipients with GERD were more likely to have CST1, characterized by high bacterial density and relative abundance of the oropharyngeal colonizing genera Prevotella and Veillonella. GERD was associated with more frequent transitions to CST1. CST1 was associated with lower inflammatory cytokine concentrations than pathogen-dominated CST3 across the range of microbial densities observed. Cox proportional hazard models revealed associations between CST3 and the development of ALAD/CLAD. Nissen fundoplication decreased bacterial load and proinflammatory cytokines. Conclusions: GERD was associated with a high bacterial density, Prevotella- and Veillonella-dominated CST1. CST3, but not CST1 or GERD, was associated with inflammation and early development of ALAD and CLAD. Nissen fundoplication was associated with a reduction in microbial density in BAL fluid samples, especially the CST1-specific genus, Prevotella.

Glutathione Metabolism Is a Regulator of the Acute Inflammatory Response of Monocytes to (1→3)-ß-D-Glucan.

(1→3)-ß-D-Glucan (BDG) represents a potent pathogen-associated molecular pattern (PAMP) in triggering the host response to fungal and some bacterial infections. Monocytes play a key role in recognizing BDG and governing the acute host response to infections. However, the mechanisms regulating monocyte's acute response to BDG are poorly understood. We sought to investigate the response of monocytes to BDG at the epigenetic, transcriptomic, and molecular levels. Response of human monocytes to 1, 4, and 24 hours of BDG exposure was investigated using RNA-seq, ATAC-seq, H3K27ac and H3K4me1 ChIP-seq. We show that pathways including glutathione metabolism, pentose phosphate pathway, and citric acid cycle were upregulated at the epigenetic and transcriptomic levels in response to BDG exposure. Strikingly, unlike bacterial lipopolysaccharides, BDG induced intracellular glutathione synthesis. BDG exposure also induced NADP synthesis, increased NADPH/NADP ratio, and increased expression of genes involved in the pentose phosphate pathway in a GSH-dependent manner. By inhibiting GSH synthesis with L-buthionine sulfoximine (BSO) before BDG exposure we show that the GSH pathway promotes cell survival and regulates monocyte's effector functions including NO production, phagocytosis, and cytokine production. In summary, our work demonstrates that BDG induces glutathione synthesis and metabolism in monocytes, which is a major promoter of the acute functional response of monocytes to infections.

Circulating ß-d-Glucan as a Marker of Subclinical Coronary Plaque in Antiretroviral Therapy-Treated People With Human Immunodeficiency Virus.

BACKGROUND: Despite antiretroviral therapy (ART), people with human immunodeficiency virus (PWH) have increased risk of inflammatory comorbidities, including cardiovascular diseases. Gut epithelial damage, and translocation of bacterial lipopolysaccharide (LPS) or fungal ß-d-glucan (BDG) drive inflammation in ART-treated PWH. In this study, we investigated whether markers of gut damage and microbial translocation were associated with cardiovascular risk in asymptomatic ART-treated PWH. METHODS: We cross-sectionally analyzed plasma from 93 ART-treated PWH and 52 uninfected controls older than 40 years of age from the Canadian HIV and Aging Cohort. Participants were cardiovascular disease free and underwent a cardiac computed tomography (CT) to measure total coronary atherosclerotic plaque volume (TPV). Levels of bacterial LPS and gut damage markers REG3α and I-FABP were measured by enzyme-linked immunosorbent assay. Fungal BDG levels were analyzed using the Fungitell assay. RESULTS: ß-d-glucan levels but not LPS were significantly elevated in ART-treated PWH with coronary artery plaque (P = .0007). Moreover, BDG but not LPS levels correlated with TPV (r = 0.26, P = .01). Intestinal fatty acid binding protein (I-FABP) but not REG3α levels correlated with TPV (r = 0.23, P = .03). However, BDG and LPS levels were not elevated in uninfected controls with plaque. In multivariable models, elevated BDG levels were independently associated with the presence of coronary atherosclerosis in PWH but not in uninfected controls. CONCLUSIONS: Translocation of fungal BDG was associated with coronary atherosclerosis assessed by CT-scan imaging in ART-treated PWH, suggesting a human immunodeficiency virus-specific pathway leading to cardiovascular disease. Further investigation is needed to appraise causality of this association. Translocation of fungal products may represent a therapeutic target to prevent cardiovascular disease in ART-treated PWH.Plasma levels of the fungal product ß-D-Glucan, but not the bacterial product lipopolysaccharide, are associated with the presence and the size of subclinical coronary atherosclerosis plaque in people living with HIV taking antiretroviral therapy, independently of classical cardiovascular risk factors.

Anti-cytomegalovirus Immunoglobulin G Is Linked to CD4 T-cell Count Decay in Human Immunodeficiency Virus (HIV) Elite Controllers.

Elite controllers (ECs) are people living with human immunodeficiency virus (HIV) who spontaneously control viral replication without antiretroviral therapy. We observed that elevated anti-cytomegalovirus (CMV) immunoglobulin G (IgG) levels correlated with annual CD4 T-cell count decay in ECs independently of age, sex, and human leukocyte antigen (HLA) type. Elevated anti-CMV titers may favor disease progression in ECs.

Repurposing Metformin in Nondiabetic People With HIV: Influence on Weight and Gut Microbiota.

BACKGROUND: People with HIV (PWH) taking antiretroviral therapy (ART) may experience weight gain, dyslipidemia, increased risk of non-AIDS comorbidities, and long-term alteration of the gut microbiota. Both low CD4/CD8 ratio and chronic inflammation have been associated with changes in the gut microbiota of PWH. The antidiabetic drug metformin has been shown to improve gut microbiota composition while decreasing weight and inflammation in diabetes and polycystic ovary syndrome. Nevertheless, it remains unknown whether metformin may benefit PWH receiving ART, especially those with a low CD4/CD8 ratio. METHODS: In the Lilac pilot trial, we recruited 23 nondiabetic PWH receiving ART for more than 2 years with a low CD4/CD8 ratio (<0.7). Blood and stool samples were collected during study visits at baseline, after a 12-week metformin treatment, and 12 weeks after discontinuation. Microbiota composition was analyzed by 16S rDNA gene sequencing, and markers of inflammation were assessed in plasma. RESULTS: Metformin decreased weight in PWH, and weight loss was inversely correlated with plasma levels of the satiety factor GDF-15. Furthermore, metformin changed the gut microbiota composition by increasing the abundance of anti-inflammatory bacteria such as butyrate-producing species and the protective Akkermansia muciniphila. CONCLUSIONS: Our study provides the first evidence that a 12-week metformin treatment decreased weight and favored anti-inflammatory bacteria abundance in the microbiota of nondiabetic ART-treated PWH. Larger randomized placebo-controlled clinical trials with longer metformin treatment will be needed to further investigate the role of metformin in reducing inflammation and the risk of non-AIDS comorbidities in ART-treated PWH.

Plasma Levels of C-Type Lectin REG3α and Gut Damage in People With Human Immunodeficiency Virus.

BACKGROUND: Regenerating islet-derived protein 3α (REG3α) is an antimicrobial peptide secreted by intestinal Paneth cells. Circulating REG3α has been identified as a gut damage marker in inflammatory bowel diseases. People living with human immunodeficiency virus (PWH) on antiretroviral therapy (ART) present with an abnormal intestinal landscape leading to microbial translocation, persistent inflammation, and development of non-AIDS comorbidities. Herein, we assessed REG3α as a marker of gut damage in PWH. METHODS: Plasma from 169 adult PWH, including 30 elite controllers (ECs), and 30 human immunodeficiency virus (HIV)-uninfected controls were assessed. REG3α plasma levels were compared with HIV disease progression, epithelial gut damage, microbial translocation, and immune activation markers. RESULTS: Cross-sectionally, REG3α levels were elevated in untreated and ART-treated PWH compared with controls. ECs also had elevated REG3α levels compared to controls. Longitudinally, REG3α levels increased in PWH without ART and decreased in those who initiated ART. REG3α levels were inversely associated with CD4 T-cell count and CD4:CD8 ratio, while positively correlated with HIV viral load in untreated participants, and with fungal product translocation and inflammatory markers in all PWH. CONCLUSIONS: Plasma REG3α levels were elevated in PWH, including ECs. The gut inflammatory marker REG3α may be used to evaluate therapeutic interventions and predict non-AIDS comorbidity risks in PWH.

Circulating (1→3)-ß-D-glucan Is Associated With Immune Activation During Human Immunodeficiency Virus Infection.

BACKGROUND: Microbial translocation from the gut to systemic circulation contributes to immune activation during human immunodeficiency virus (HIV) infection and is usually assessed by measuring plasma levels of bacterial lipopolysaccharide (LPS). Fungal colonization in the gut increases during HIV-infection and people living with HIV (PLWH) have increased plasma levels of fungal polysaccharide (1→3)-ß-D-Glucan (ßDG). We assessed the contribution of circulating DG to systemic immune activation in PLWH. METHODS: Cross-sectional and longitudinal assessments of plasma ßDG levels were conducted along with markers of HIV disease progression, epithelial gut damage, bacterial translocation, proinflammatory cytokines, and ßDG-specific receptor expression on monocytes and natural killer (NK) cells. RESULTS: Plasma ßDG levels were elevated during early and chronic HIV infection and persisted despite long-term antiretroviral therapy (ART). ßDG increased over 24 months without ART but remained unchanged after 24 months of treatment. ßDG correlated negatively with CD4 T-cell count and positively with time to ART initiation, viral load, intestinal fatty acid-binding protein, LPS, and soluble LPS receptor soluble CD14 (sCD14). Elevated ßDG correlated positively with indoleamine-2,3-dioxygenase-1 enzyme activity, regulatory T-cell frequency, activated CD38+Human Leukocyte Antigen - DR isotype (HLA-DR)+ CD4 and CD8 T cells and negatively with Dectin-1 and NKp30 expression on monocytes and NK cells, respectively. CONCLUSIONS: PLWH have elevated plasma ßDG in correlation with markers of disease progression, gut damage, bacterial translocation, and inflammation. Early ART initiation prevents further ßDG increase. This fungal antigen contributes to immune activation and represents a potential therapeutic target to prevent non-acquired immunodeficiency syndrome events.

Cytomegalovirus Seropositivity Is Associated With Increased Microbial Translocation in People Living With Human Immunodeficiency Virus and Uninfected Controls.

BACKGROUND: Cytomegalovirus (CMV) seropositivity and anti-CMV immunoglobulin G (IgG) levels are associated with adverse health outcomes in elderly populations. Among people living with human immunodeficiency virus (PLWH), CMV seropositivity has been associated with persistent CD8 T-cell elevation and increased risk of developing non-AIDS comorbidities despite long-term antiretroviral therapy (ART). Herein, we investigated whether CMV seropositivity and elevation of anti-CMV IgG levels were associated with increased epithelial gut damage, microbial translocation, and systemic inflammation. METHODS: A total of 150 PLWH (79 ART-naive and 71 ART-treated) were compared to 26 without human immunodeficiency virus (HIV) infection (uninfected controls). Plasma markers of HIV disease progression, epithelial gut damage, microbial translocation, nonspecific B-cell activation, anti-CMV and anti-Epstein-Barr virus (EBV) IgG levels, and proinflammatory cytokines were measured. RESULTS: CMV seropositivity and elevated anti-CMV IgG levels were associated with markers of epithelial gut damage, microbial translocation, and inflammation in PLWH and participants without HIV infection. In contrast, total nonspecific IgG, immunoglobulin M, immunoglobulin A, and anti-EBV IgG levels were not associated with these markers. CMV seropositivity was associated with markers of epithelial gut damage, microbial translocation, and inflammation independent of sociodemographic and behavioral characteristics of the study population. CONCLUSIONS: CMV-seropositive people with and without HIV had increased epithelial gut damage, microbial translocation, and inflammation. Furthermore, anti-CMV IgG levels were independently associated with increased epithelial gut damage and microbial translocation. CMV coinfection may partially explain persistent gut damage, microbial translocation, and inflammation in ART-treated PLWH.

Association between lymphocyte subsets and cytomegalovirus infection status among patients with systemic lupus erythematosus: A pilot study.

This study aimed to determine the association between different lymphocyte subsets and cytomegalovirus (CMV) infection status in patients with systemic lupus erythematosus (SLE). We performed a retrospective study among SLE patients with CMV infection and collected patient socio-demographic and clinical characteristics, as well as their recorded circulating lymphocyte subsets. Univariate and multivariable logistic regression analyses examined the relationship between CMV infection status and lymphocyte subset counts. We included 125 hospitalized patients with SLE, consisting of 88 with documented CMV infection and 37 without any evidence of CMV or other infections. Among the 88 CMV-infected patients, 65 (73.8%) patients developed CMV disease and 23 (26.2%) presented as CMV viremia. Compared to uninfected patients (1520 ±â€Š101 cells/µL), lymphocytes remained stable among those with CMV viremia (1305 ±â€Š272 cells/µL, P = .995). However, compared to their uninfected counterparts, there was a marked decrease in lymphocytes among patients with CMV disease (680 ±â€Š513 cells/µL, P < .001). Analysis of lymphocyte subsets via flow cytometry showed that CD4+ T cell, CD8+ T cell, and natural killer cell counts were lower among those with CMV disease compared to those with CMV viremia and those without infection. Further, multivariable analysis showed that total lymphocyte (odds ratio [OR] 0.999, 95% confidence interval [CI] 0.998-1.000, P = .007) and CD4+ T cell counts (OR 0.99, 95% CI 0.992-0.998, P = .003) were negatively associated with CMV disease. Our findings support a potential inverse relationship between lymphopenia, specifically CD4+ T-cell lymphopenia, and CMV disease among hospitalized SLE patients.

Circulating LPS and (1→3)-ß-D-Glucan: A Folie à Deux Contributing to HIV-Associated Immune Activation.

Immune activation is the driving force behind the occurrence of AIDS and non-AIDS events, and is only partially reduced by antiretroviral therapy (ART). Soon after HIV infection, intestinal CD4+ T cells are depleted leading to epithelial gut damage and subsequent translocation of microbes and/or their products into systemic circulation. Bacteria and fungi are the two most abundant populations of the gut microbiome. Circulating lipopolysaccharide (LPS) and (1→3)-ß-D-Glucan (ßDG), major components of bacterial and fungal cell walls respectively, are measured as markers of microbial translocation in the context of compromised gut barriers. While LPS is a well-known inducer of innate immune activation, ßDG is emerging as a significant source of monocyte and NK cell activation that contributes to immune dysfunction. Herein, we critically evaluated recent literature to untangle the respective roles of LPS and ßDG in HIV-associated immune dysfunction. Furthermore, we appraised the relevance of LPS and ßDG as biomarkers of disease progression and immune activation on ART. Understanding the consequences of elevated LPS and ßDG on immune activation will provide insight into novel therapeutic strategies against the occurrence of AIDS and non-AIDS events.

CXCL13 as a Biomarker of Immune Activation During Early and Chronic HIV Infection.

Background: CXCL13 is preferentially secreted by Follicular Helper T cells (TFH) to attract B cells to germinal centers. Plasma levels of CXCL13 have been reported to be elevated during chronic HIV-infection, however there is limited data on such elevation during early phases of infection and on the effect of ART. Moreover, the contribution of CXCL13 to disease progression and systemic immune activation have been partially defined. Herein, we assessed the relationship between plasma levels of CXCL13 and systemic immune activation. Methods: Study samples were collected in 114 people living with HIV (PLWH) who were in early (EHI) or chronic (CHI) HIV infection and 35 elite controllers (EC) compared to 17 uninfected controls (UC). A subgroup of 11 EHI who initiated ART and 14 who did not were followed prospectively. Plasma levels of CXCL13 were correlated with CD4 T cell count, CD4/CD8 ratio, plasma viral load (VL), markers of microbial translocation [LPS, sCD14, and (1→3)-ß-D-Glucan], markers of B cell activation (total IgG, IgM, IgA, and IgG1-4), and inflammatory/activation markers like IL-6, IL-8, IL-1ß, TNF-α, IDO-1 activity, and frequency of CD38+HLA-DR+ T cells on CD4+ and CD8+ T cells. Results: Plasma levels of CXCL13 were elevated in EHI (127.9 ± 64.9 pg/mL) and CHI (229.4 ± 28.5 pg/mL) compared to EC (71.3 ± 20.11 pg/mL), and UC (33.4 ± 14.9 pg/mL). Longitudinal analysis demonstrated that CXCL13 remains significantly elevated after 14 months without ART (p < 0.001) and was reduced without normalization after 24 months on ART (p = 0.002). Correlations were observed with VL, CD4 T cell count, CD4/CD8 ratio, LPS, sCD14, (1→3)-ß-D-Glucan, total IgG, TNF-α, Kynurenine/Tryptophan ratio, and frequency of CD38+HLA-DR+ CD4 and CD8 T cells. In addition, CMV+ PLWH presented with higher levels of plasma CXCL13 than CMV- PLWH (p = 0.005). Conclusion: Plasma CXCL13 levels increased with HIV disease progression. Early initiation of ART reduces plasma CXCL13 and B cell activation without normalization. CXCL13 represents a novel marker of systemic immune activation during early and chronic HIV infection and may be used to predict the development of non-AIDS events.

Use of (1→3)-ß-d-glucan for diagnosis and management of invasive mycoses in HIV-infected patients.

People living with HIV (PLHIV) are highly vulnerable to invasive fungal infections (IFIs) due to their immune dysfunction. Diagnosis and treatment of IFIs remain challenging due to the requirement of deep tissue sampling to visualise and culture fungi before initiating treatment. Such techniques are less practical in resource-limited settings due to their cost and requirement of relatively invasive procedures. Hence, identification of surrogate markers for the early diagnosis and therapeutic monitoring of IFIs is required. Recent studies have shown that (1→3)-ß-d-glucan (BDG), a major fungal cell wall antigen, represents a promising soluble marker for the presumptive diagnosis and therapeutic monitoring of IFIs in HIV-infected patients. Herein, we review findings on the merits of BDG assays in the diagnosis of IFIs and monitoring of antifungal therapies for PLHIV. Conversely to other types of immunocompromised patients, HIV infection is associated with gut damage and subsequent bacterial and fungal translocation leading to elevated BDG plasma levels.

The evaluation of risk-benefit ratio for gut tissue sampling in HIV cure research.

INTRODUCTION: Antiretroviral therapy (ART) does not cure HIV infection due to the persistence of HIV reservoirs in long-lived memory CD4 T cells present in the blood, lymph nodes, intestinal tract, and other tissues. Interest grows in obtaining gut-tissue samples for HIV persistence studies, which poses an ethical challenge to provide study volunteers with adequate information on risks and benefits. Herein we assess the risks and benefits of undergoing gut biopsy procedures for HIV pathogenesis and reservoir studies. METHODS: A group discussion was organised with physicians and community representatives on performing either a flexible sigmoidoscopy or a colonoscopy. Consensus was reached on conducting colonoscopy in persons ≥50 years. Thirty HIV-infected, ART-treated and nine uninfected participants were recruited. Colonoscopy was performed to collect 30 gut mucosal biopsies. When present, polyps were removed and abnormal mucosal findings were biopsied for pathological analysis. Participants were interviewed on potential discomfort following colonoscopic examination. RESULTS: The HIV-infected and uninfected groups were comparable in terms of age and gender with more men who have sex with men (MSM) in the former group. Abnormal colonoscopic findings were observed in 43.6% of all the participants and did not differ by HIV status. In total, 24 polyps were removed with a higher mean number of polyps removed in HIV-infected versus uninfected participants (1.7 vs 1.0, P=0.013). The number of polyps marginally correlated with inverted CD4:CD8 ratio. Based on our findings, colonoscopic examination was safe to use for gut biopsy procedures where almost half of the participants had polyps removed. CONCLUSION: Participation in the study provided colon cancer screening as an ancillary benefit that participants could have received in standard medical care, thus mitigating burdens of invasive procedures. Dialogue between community representatives and clinical researchers can increase participation and advance HIV cure research.