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Martin Hoenigl, Josué Pérez-Santiago, Masato Nakazawa, Michelli Faria de Oliveira, Yonglong Zhang, Malcolm A Finkelman, Scott Letendre, Davey Smith, Sara Gianella
BACKGROUND: The extent of gut microbial translocation, which plays roles in HIV disease progression and non-AIDS comorbidities, appears to vary with the composition of the gut microbiome, particularly the presence of Lactobacillales, which reduce mucosal injury. While low proportions of Lactobacillales in the distal gut microbiome are a very promising indicator of microbial translocation, measurement is expensive and complicated and not feasible for clinical routine. (1→3)-β-d-Glucan (BDG) is a component of most fungal cell walls and might be a surrogate marker for Lactobacillales proportion in the gut and a useful indicator of HIV-associated gut injury...
2016: Frontiers in Immunology
Irini Sereti, Shelly J Krebs, Nittaya Phanuphak, James L Fletcher, Bonnie Slike, Suteeraporn Pinyakorn, Robert J O'Connell, Adam Rupert, Nicolas Chomont, Victor Valcour, Jerome H Kim, Merlin L Robb, Nelson L Michael, Daniel C Douek, Jintanat Ananworanich, Netanya S Utay
BACKGROUND:  Serious non-AIDS events cause substantial morbidity and mortality despite HIV suppression with antiretroviral therapy (ART). Biomarkers of inflammation, coagulation cascade activation, and fibrosis predict these end-organ events. We aimed to determine whether ART initiation during acute HIV infection would attenuate changes in these biomarker levels. METHODS:  Plasma samples were obtained from participants starting ART during acute HIV infection, chronic HIV infection, and HIV-uninfected participants, from Bangkok, Thailand...
October 12, 2016: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
Carolina Scagnolari, Giuseppe Corano Scheri, Carla Selvaggi, Ivan Schietroma, Saeid Najafi Fard, Andrea Mastrangelo, Noemi Giustini, Sara Serafino, Claudia Pinacchio, Paolo Pavone, Gianfranco Fanello, Giancarlo Ceccarelli, Vincenzo Vullo, Gabriella d'Ettorre
Recently the tryptophan pathway has been considered an important determinant of HIV-1 infected patients' quality of life, due to the toxic effects of its metabolites on the central nervous system (CNS). Since the dysbiosis described in HIV-1 patients might be responsible for the microbial translocation, the chronic immune activation, and the altered utilization of tryptophan observed in these individuals, we speculated a correlation between high levels of immune activation markers in the cerebrospinal fluid (CSF) of HIV-1 infected patients and the over-expression of indolamine-2,3-dioxygenase (IDO) at the gut mucosal surface...
2016: International Journal of Molecular Sciences
Trevor A Crowell, James Lk Fletcher, Irini Sereti, Suteeraporn Pinyakorn, Robin Dewar, Shelly J Krebs, Nitiya Chomchey, Rungsun Rerknimitr, Alexandra Schuetz, Nelson L Michael, Nittaya Phanuphak, Nicolas Chomont, Jintanat Ananworanich
INTRODUCTION: Colonic infiltration by HIV occurs soon after infection, establishing a persistent viral reservoir and a barrier to cure. We investigated virologic and immunologic correlates of detectable colonic HIV RNA during acute HIV infection (AHI) and their response to antiretroviral treatment (ART). METHODS: From 49,458 samples screened for HIV, 74 participants were enrolled during AHI and 41 consented to optional sigmoidoscopy, HIV RNA was categorized as detectable (≥50 copies/mg) or undetectable in homogenized colon biopsy specimens...
2016: Journal of the International AIDS Society
Joseph C Mudd, Jason M Brenchley
Distinct pathological events occur within the gastrointestinal (GI) tract of Asian macaques with progressive simian immunodeficiency virus (SIV) infection and humans with human immunodeficiency virus type 1 (HIV-1) infection that are critical in shaping disease course. These events include depletion and functional alteration of GI-resident CD4(+) T cells, loss of antigen-presenting cells, loss of innate lymphocytes, and possible alterations to the composition of the gut microbiota. These contribute to structural damage to the GI tract and systemic translocation of GI tract microbial products...
October 1, 2016: Journal of Infectious Diseases
Najib Aziz, Roger Detels, L Cindy Chang, Anthony W Butch
OBJECTIVE: Uncontrolled HIV infection progresses to the depletion of systemic and mucosal CD4 and AIDS. Early HIV infection may be associated with increases in the concentration of MIP-3α in the blood and gut fluids. MIP-3α/CCL20 is the only chemokine known to interact with CCR6 receptors which are expressed on immature dendritic cells and both effector and memory CD8(+) and CD4(+) T cells. The role and prognostic value of blood levels of MIP-3α in HIV-infected individuals has yet to be described...
July 2016: Journal of AIDS & Clinical Research
Vanessa Sue Wacleche, Jean-Philippe Goulet, Annie Gosselin, Patricia Monteiro, Hugo Soudeyns, Rémi Fromentin, Mohammad-Ali Jenabian, Shant Vartanian, Steven G Deeks, Nicolas Chomont, Jean-Pierre Routy, Petronela Ancuta
BACKGROUND: Th17 cells are permissive to HIV-1 infection and their depletion from the gut of infected individuals leads to microbial translocation, a major cause for non-AIDS co-morbidities. Most recent evidence supports the contribution of long-lived Th17 cells to HIV persistence during antiretroviral therapy (ART). However, the identity of long-lived Th17 cells remains unknown. RESULTS: Here, we performed an in-depth transcriptional and functional characterization of four distinct Th17 subsets and investigated their contribution to HIV reservoir persistence during ART...
2016: Retrovirology
Grégory Dubourg, Jean-Christophe Lagier, Sophie Hüe, Mathieu Surenaud, Dipankar Bachar, Catherine Robert, Caroline Michelle, Isabelle Ravaux, Saadia Mokhtari, Matthieu Million, Andreas Stein, Philippe Brouqui, Yves Levy, Didier Raoult
OBJECTIVES: Gut microbiota modifications occurring during HIV infection have recently been associated with inflammation and microbial translocation. However, discrepancies between studies justified a comprehensive analysis performed on a large sample size. DESIGN AND METHODS: In a case-control study, next-generation sequencing of the 16S rRNA gene was applied to the faecal microbiota of 31 HIV-infected patients, of whom 18 were treated with antiretroviral treatment (ART), compared with 27 healthy controls...
2016: BMJ Open Gastroenterology
Babs Verstrepen, Ivonne G Nieuwenhuis, Petra Mooij, Ernst J Verschoor, Zahra C Fagrouch, Ivanela Kondova, André Boonstra, Gerrit Koopman
During HIV infection sCD14 is up-regulated as a consequence of pathological disruption of the gut epithelial barrier which results in increased microbial translocation. Also in HCV infected patients with advanced liver fibrosis, increased levels of sCD14 have been reported. Since the liver plays an important role in clearance of translocated bacterial products, hepatic fibrosis may negatively affect clearance, and thus contribute to higher sCD14 levels. Chimpanzees (Pan troglodytes) infected with hepatitis C virus typically show no signs of liver fibrosis...
August 16, 2016: Journal of General Virology
Nicholas T Funderburg, Morgan Boucher, Abdus Sattar, Manjusha Kulkarni, Danielle Labbato, Bruce I Kinley, Grace A McComsey
INTRODUCTION: Altered gastrointestinal (GI) barrier integrity and subsequent microbial translocation may contribute to immune activation in HIV infection. We have reported that rosuvastatin improved several markers of immune activation in HIV+ participants, but the effect of statin treatment on markers of GI barrier dysfunction is unknown. METHODS: SATURN-HIV is a randomized, double-blind, placebo-controlled trial assessing the effect of rosuvastatin (10mg/daily) on markers of cardiovascular disease, inflammation, and immune activation in ART-treated patients...
2016: Pathogens & Immunity
Andrea Mencarelli, Sabrina Cipriani, Daniela Francisci, Luca Santucci, Franco Baldelli, Eleonora Distrutti, Stefano Fiorucci
Targeted disruption of leukocyte trafficking to the gut represents a promising approach for the treatment of inflammatory bowel diseases (IBDs). CCR5, the shared receptor for MIP1α and β and RANTES, is expressed by multiple leukocytes. Here, we aimed to determine the role of CCR5 in mediating leukocyte trafficking in models of colitis, and evaluate the therapeutic potential of maraviroc, an orally active CCR5 antagonist used in the treatment of CCR5-tropic HIV. Acute and chronic colitis were induced by administration of DSS or TNBS to wild-type and CCR5(-/-) mice or adoptive transfer of splenic naïve CD4(+) T-cells from wild type or CCR5(-/-) mice into RAG-1(-/-)...
2016: Scientific Reports
Joy Guedia, Paola Brun, Sukhada Bhave, Sylvia Fitting, Minho Kang, William L Dewey, Kurt F Hauser, Hamid I Akbarali
The loss of gut epithelium integrity leads to translocation of microbes and microbial products resulting in immune activation and drives systemic inflammation in acquired immunodeficiency syndrome (AIDS) patients. Although viral loads in HIV patients are significantly reduced in the post-cART era, inflammation and immune activation persist and can lead to morbidity. Here, we determined the interactive effects of the viral protein HIV-1 Tat and lipopolysaccharide (LPS) on enteric neurons and glia. Bacterial translocation was significantly enhanced in Tat-expressing (Tat+) mice...
2016: Scientific Reports
Angela A S Sena, Tiffany Glavan, Guochun Jiang, Sumathi Sankaran-Walters, Irina Grishina, Satya Dandekar, Luiz R Goulart
HIV-1 disease progression is paradoxically characterized by systemic chronic immune activation and gut mucosal immune dysfunction, which is not fully defined. Annexin A1 (ANXA1), an inflammation modulator, is a potential link between systemic inflammation and gut immune dysfunction during the simian immunodeficiency virus (SIV) infection. Gene expression of ANXA1 and cytokines were assessed in therapy-naïve rhesus macaques during early and chronic stages of SIV infection and compared with SIV-negative controls...
2016: Scientific Reports
Zongxin Ling, Changzhong Jin, Tiansheng Xie, Yiwen Cheng, Lanjuan Li, Nanping Wu
The available evidence suggests that alterations in gut microbiota may be tightly linked to the increase in microbial translocation and systemic inflammation in patients with human immunodeficiency virus 1 (HIV-1) infection. We profiled the fecal microbiota as a proxy of gut microbiota by parallel barcoded 454-pyrosequencing in 67 HIV-1-infected patients (32 receiving highly active antiretroviral therapy [HAART] and 35 HAART naïve) and 16 healthy controls from a Chinese population. We showed that α-diversity indices did not differ significantly between the healthy control and HIV-1-infected patients...
2016: Scientific Reports
Clare Logan, Mike B J Beadsworth, Nick J Beeching
PURPOSE OF REVIEW: The review examines the changing causes and the investigation of infectious and noninfectious diarrhoea in individuals with HIV. RECENT FINDINGS: Despite the excellent prognosis conferred by combination antiretroviral therapy, diarrhoea is still common in HIV-positive individuals and is associated with reduced quality of life and survival. There is increasing interest in the importance of Th17 and Th22 T cells in the maintenance of mucosal immunity within the gut, and in the role of the gut microbiome in gut homeostasis...
October 2016: Current Opinion in Infectious Diseases
Claire Deleage, Alexandra Schuetz, W Gregory Alvord, Leslie Johnston, Xing-Pei Hao, David R Morcock, Rungsun Rerknimitr, James L K Fletcher, Suwanna Puttamaswin, Nittaya Phanuphak, Robin Dewar, Joseph M McCune, Irini Sereti, Merlin Robb, Jerome H Kim, Timothy W Schacker, Peter Hunt, Jeffrey D Lifson, Jintanat Ananworanich, Jacob D Estes
Early after HIV infection there is substantial depletion of CD4(+) T cells in the gastrointestinal (GI) tract lamina propria (LP), with associated epithelial barrier damage, leading to microbial translocation and systemic inflammation and immune activation. In this study, we analyzed these early events in the GI tract in a cohort of Thai acute HIV-infected patients and determined the effect of early combination antiretroviral treatment (cART). HIV-uninfected and chronically and acutely HIV-infected patients at different Fiebig stages (I-V) underwent colonic biopsies and then received cART...
July 7, 2016: JCI Insight
Sergio Serrano-Villar, David Rojo, Mónica Martínez-Martínez, Simon Deusch, Jorge F Vázquez-Castellanos, Rafael Bargiela, Talía Sainz, Mar Vera, Santiago Moreno, Vicente Estrada, María José Gosalbes, Amparo Latorre, Jana Seifert, Coral Barbas, Andrés Moya, Manuel Ferrer
While changes in gut microbial populations have been described in human immuno-deficiency virus (HIV)-infected patients undergoing antiretroviral therapy (ART), the mechanisms underlying the contributions of gut bacteria and their molecular agents (metabolites and proteins) to immune recovery remain unexplored. To study this, we examined the active fraction of the gut microbiome, through examining protein synthesis and accumulation of metabolites inside gut bacteria and in the bloodstream, in 8 healthy controls and 29 HIV-infected individuals (6 being longitudinally studied)...
June 2016: EBioMedicine
Anna Coutsoudis, Brodie Daniels, Eshia Moodley-Govender, Noluthando Ngomane, Linda Zako, Elizabeth Spooner, Photini Kiepiela, Shabashini Reddy, Louise Kuhn, Gita Ramjee
INTRODUCTION: No randomised controlled trial (RCT) has examined the efficacy of cotrimoxazole (CTX) prophylaxis in HIV-exposed uninfected (HEU) infants during the breastfeeding period, in this new era of effective prevention of mother-to-child transmission (PMTCT) prophylaxis. The efficacy of CTX prophylaxis has presently been demonstrated only in HIV-infected children. The absence of proven benefits in HEU breastfed infants associated with infectious diseases justifies an RCT as proposed...
2016: BMJ Open
Kevin Raehtz, Ivona Pandrea, Cristian Apetrei
African NHPs are infected by over 40 different simian immunodeficiency viruses. These viruses have coevolved with their hosts for long periods of time and, unlike HIV in humans, infection does not generally lead to disease progression. Chronic viral replication is maintained for the natural lifespan of the host, without loss of overall immune function. Lack of disease progression is not correlated with transmission, as SIV infection is highly prevalent in many African NHP species in the wild. The exact mechanisms by which these natural hosts of SIV avoid disease progression are still unclear, but a number of factors might play a role, including: (i) avoidance of microbial translocation from the gut lumen by preventing or repairing damage to the gut epithelium; (ii) control of immune activation and apoptosis following infection; (iii) establishment of an anti-inflammatory response that resolves chronic inflammation; (iv) maintenance of homeostasis of various immune cell populations, including NK cells, monocytes/macrophages, dendritic cells, Tregs, Th17 T-cells, and γδ T-cells; (v) restriction of CCR5 availability at mucosal sites; (vi) preservation of T-cell function associated with down-regulation of CD4 receptor...
July 6, 2016: Infection, Genetics and Evolution
Gregory M Anstead
In 1915, a British medical officer on the Western Front reported on a soldier with relapsing fever, headache, dizziness, lumbago, and shin pain. Within months, additional cases were described, mostly in frontline troops, and the new disease was called trench fever. More than 1 million troops were infected with trench fever during World War 1, with each affected soldier unfit for duty for more than 60 days. Diagnosis was challenging, because there were no pathognomonic signs and symptoms and the causative organism could not be cultured...
August 2016: Lancet Infectious Diseases
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