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Pattern of microbial translocation in patients living with HIV-1 from Vietnam, Ethiopia and Sweden.

ABSTRACT: The role of microbial translocation (MT) in HIV patients living with HIV from low- and middle-income countries (LMICs) is not fully known. The aim of this study is to investigate and compare the patterns of MT in patients from Vietnam, Ethiopia and Sweden.Cross-sectional samples were obtained from treatment-naïve patients living with HIV-1 and healthy controls from Vietnam (n=83; n=46), Ethiopia (n=9492; n=50) and Sweden (n=51; n=19). Longitudinal samples were obtained from a subset of the Vietnamese (n=24) in whom antiretroviral therapy (ART) and tuberculostatics were given. Plasma lipopolysaccharide (LPS), sCD14 and anti-flagellin IgG were determined by the endpoint chromogenic Limulus Amebocyte Assay and enzyme-linked immunosorbent assay.All three biomarkers were significantly increased in patients living with HIV-1 from all countries as compared to controls. No differences were found between males and females. Vietnamese and Ethiopian patients had significantly higher levels of anti-flagellin IgG and LPS, as compared to Swedes. ART reduced these levels for the Vietnamese. Vietnamese patients given tuberculostatics at initiation of ART had significantly lower levels of anti-flagellin IgG and higher sCD14. The biomarkers were lower in Vietnamese who did not develop opportunistic infection.Higher MT is common in patients living with HIV compared to healthy individuals, and in patients from LMICs compared to patients from a high-income country. Treatment with tuberculostatics decreased MT while higher levels of MT are associated with a poorer clinical outcome.

SUBMITTER: Abdurahman S

PROVIDER: S-EPMC3902178 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Pattern of microbial translocation in patients living with HIV-1 from Vietnam, Ethiopia and Sweden.

Abdurahman Samir S Barqasho Babilonia B Nowak Piotr P Cuong Do Duy do D Amogné Wondwossen W Larsson Mattias M Lindquist Lars L Marrone Gaetano G Sönnerborg Anders A

Journal of the International AIDS Society 20140124

<h4>Introduction</h4>The role of microbial translocation (MT) in HIV patients living with HIV from low- and middle-income countries (LMICs) is not fully known. The aim of this study is to investigate and compare the patterns of MT in patients from Vietnam, Ethiopia and Sweden.<h4>Methods</h4>Cross-sectional samples were obtained from treatment-naïve patients living with HIV-1 and healthy controls from Vietnam (n=83; n=46), Ethiopia (n=9492; n=50) and Sweden (n=51; n=19). Longitudinal samples wer ...[more]

PMID: 24461466

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Project description:BackgroundDespite effective antiretroviral therapy (ART), patients with chronic human immunodeficiency virus (HIV) infection have increased microbial translocation and systemic inflammation. Alterations in the intestinal microbiota may play a role in microbial translocation and inflammation.MethodsWe profiled the fecal microbiota by pyrosequencing the gene encoding 16S ribosomal RNA (rRNA) and measured markers of microbial translocation and systemic inflammation in 21 patients who had chronic HIV infection and were receiving suppressive ART (cases) and 16 HIV-uninfected controls.ResultsThe fecal microbial community composition was significantly different between cases and controls. The relative abundance of Proteobacteria, Gammaproteobacteria, Enterobacteriales, Enterobacteriaceae, Erysipelotrichi, Erysipelotrichales, Erysipelotrichaceae, and Barnesiella was significantly enriched in cases, whereas that of Rikenellaceae and Alistipes was depleted. The plasma soluble CD14 level (sCD14) was significantly higher and the endotoxin core immunoglobulin M (IgM) level lower in cases, compared with controls. There were significant positive correlations between the relative abundances of Enterobacteriales and Enterobacteriaceae and the sCD14 level; the relative abundances of Gammaproteobacteria, Enterobacteriales, and Enterobacteriaceae and the interleukin 1β (IL-1β) level; the relative abundances of Enterobacteriales and Enterobacteriaceae and the interferon γ level; and the relative abundances of Erysipelotrichi and Barnesiella and the TNF-α level. There were negative correlations between endotoxin core IgM and IL-1β levels.ConclusionsPatients who have chronic HIV infection and are receiving suppressive ART display intestinal dysbiosis associated with increased microbial translocation and significant associations between specific taxa and markers of microbial translocation and systemic inflammation. This was an exploratory study, the findings of which need to be confirmed.

Project description:BackgroundDespite the effectiveness of cART, people living with HIV still experience an increased risk of serious non-AIDS events, as compared to the HIV negative population. Whether pre-cART microbial translocation (MT) and systemic inflammation might predict morbidity/mortality during suppressive cART, independently of other known risk factors, is still unclear. Thus, we aimed to investigate the role of pre-cART inflammation and MT as predictors of clinical progression in HIV+ patients enrolled in the Icona Foundation Study Cohort.MethodsWe included Icona patients with ≥2 vials of plasma stored within 6 months before cART initiation and at least one CD4 count after therapy available. Circulating biomarker: LPS, sCD14, EndoCab, hs-CRP. Kaplan-Meier curves and Cox regression models were used. We defined the endpoint of clinical progression as the occurrence of a new AIDS-defining condition, severe non-AIDS condition (SNAEs) or death whichever occurred first. Follow-up accrued from the data of starting cART and was censored at the time of last available clinical visit. Biomarkers were evaluated as both binary (above/below median) and continuous variables (logescale).ResultsWe studied 486 patients with 125 clinical events: 39 (31%) AIDS, 66 (53%) SNAEs and 20 (16%) deaths. Among the analyzed MT and pro-inflammatory markers, hs-CRP seemed to be the only biomarker retaining some association with the endpoint of clinical progression (i.e. AIDS/SNAEs/death) after adjustment for confounders, both when the study population was stratified according to the median of the distribution (1.51 mg/L) and when the study population was stratified according to the 33% percentiles of the distribution (low 0.0-1.1 mg/L; intermediate 1.2-5.3 mg/L; high > 5.3 mg/L). In particular, the higher the hs-CRP values, the higher the risk of clinical progression (p = 0.056 for median-based model; p = 0.002 for 33% percentile-based model).ConclusionsOur data carries evidence for an association between the risk of disease progression after cART initiation and circulating pre-cART hs-CRP levels but not with levels of MT. These results suggest that pre-therapy HIV-driven pro-inflammatory milieu might overweight MT and its downstream immune-activation.

Project description:IntroductionContraception can help to meet family planning goals for women living with HIV (WLHIV) as well as to support the prevention of mother to child transmission of HIV (PMTCT). However, there is little research into the contraceptive practice among sexually active WLHIV in Ethiopia. Therefore, we aimed to examine contraceptive practice among sexually active WLHIV in western Ethiopia and identify the factors that influenced such practice using the Health Belief Model (HBM).MethodsA facility-based cross-sectional survey of 360 sexually active WLHIV was conducted from 19th March to 22nd June 2018 in western Ethiopia. The eligible participants were WLHIV aged between 18 and 49 years who reported being fecund and sexually active within the previous six months but were not pregnant and not wanting to have another child within two years. Modified Poisson regression analyses were conducted to identify factors that influenced contraceptive practice among sexually active WLHIV in western Ethiopia.ResultsAmong sexually active WLHIV (n = 360), 75% used contraception with 25% having unmet needs. Of the contraceptive users, 44.8% used injectables, 37.4% used condoms and 28.5% used implants. Among 152 recorded births in the last five years, 17.8% were reported as mistimed and 25.7% as unwanted. Compared to WLHIV having no child after HIV diagnosis, having two or more children after HIV diagnosis (Adjusted Prevalence Ratio [APR] = 1.31; 95%CI 1.09-1.58) was associated with increased risk of contraceptive practice. However, sexually active unmarried WLHIV (APR = 0.69; 95%CI 0.50-0.95) were less likely to use any contraception compared to their sexually active married counterparts. Importantly, high perceived susceptibility (APR = 1.49; 95%CI 1.20-1.86) and medium perceived susceptibility (APR = 1.55; 95%CI 1.28-1.87) towards unintended pregnancy were associated with higher risk of contraceptive use than WLHIV with low perceived susceptibility.ConclusionsAlthough contraceptive use amongst sexually active WLHIV was found to be high, our findings highlight the need for strengthening family planning services given the high rate of unintended pregnancies, the high rate of unmet needs for contraception, as well as the lower efficacy with some of the methods. Our findings also suggest that the HBM would be a valuable framework for healthcare providers, programme planners and policymakers to develop guidelines and policies for contraceptive counselling and choices.

Project description:While several clinical studies have shown that HIV-1 infection is associated with increased permeability of the intestinal tract, there is very little understanding of the mechanisms underlying HIV-induced impairment of mucosal barriers. Here we demonstrate that exposure to HIV-1 can directly breach the integrity of mucosal epithelial barrier, allowing translocation of virus and bacteria. Purified primary epithelial cells (EC) isolated from female genital tract and T84 intestinal cell line were grown to form polarized, confluent monolayers and exposed to HIV-1. HIV-1 X4 and R5 tropic laboratory strains and clinical isolates were seen to reduce transepithelial resistance (TER), a measure of monolayer integrity, by 30-60% following exposure for 24 hours, without affecting viability of cells. The decrease in TER correlated with disruption of tight junction proteins (claudin 1, 2, 4, occludin and ZO-1) and increased permeability. Treatment of ECs with HIV envelope protein gp120, but not HIV tat, also resulted in impairment of barrier function. Neutralization of gp120 significantly abrogated the effect of HIV. No changes to the barrier function were observed when ECs were exposed to Env defective mutant of HIV. Significant upregulation of inflammatory cytokines, including TNF-alpha, were seen in both intestinal and genital epithelial cells following exposure to HIV-1. Neutralization of TNF-alpha reversed the reduction in TERs. The disruption in barrier functions was associated with viral and bacterial translocation across the epithelial monolayers. Collectively, our data shows that mucosal epithelial cells respond directly to envelope glycoprotein of HIV-1 by upregulating inflammatory cytokines that lead to impairment of barrier functions. The increased permeability could be responsible for small but significant crossing of mucosal epithelium by virus and bacteria present in the lumen of mucosa. This mechanism could be particularly relevant to mucosal transmission of HIV-1 as well as immune activation seen in HIV-1 infected individuals.

Dataset Information

Pattern of microbial translocation in patients living with HIV-1 from Vietnam, Ethiopia and Sweden.

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Pattern of microbial translocation in patients living with HIV-1 from Vietnam, Ethiopia and Sweden.

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