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HIV Elite Controllers

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https://www.readbyqxmd.com/read/29135490/the-microbiome-and-hiv-persistence-implications-for-viral-remission-and-cure
#1
Wei Li A Koay, Lilly V Siems, Deborah Persaud
PURPOSE OF REVIEW: This article discusses the interaction between HIV infection, the gut microbiome, inflammation and immune activation, and HIV reservoirs, along with interventions to target the microbiome and their implications for HIV remission and cure. RECENT FINDINGS: Most studies show that HIV-infected adults have a gut microbiome associated with decreased bacterial richness and diversity, and associated systemic inflammation and immune activation. A unique set of individuals, elite controllers, who spontaneously control HIV replication, have a similar microbiome to HIV-uninfected individuals...
November 10, 2017: Current Opinion in HIV and AIDS
https://www.readbyqxmd.com/read/29122683/high-cxcl10-ip-10-levels-are-a-hallmark-in-the-clinical-evolution-of-the-hiv-infection
#2
Jacqueline María Valverde-Villegas, Rúbia Marília de Medeiros, Joel Henrique Ellwanger, Breno Riegel Santos, Marineide Gonçalves de Melo, Sabrina Esteves de Matos Almeida, José Artur Bogo Chies
The aim of this study was to investigate the modulation of plasma CXCL10, CCL20, CCL22, CCL2, CCL17 and CCL24 levels in HIV-positive patients grouped according to extreme phenotypes of progression to AIDS, and at different stages of HIV infection. HIV-positive individuals with extreme phenotypes of AIDS progression (n=58) at different clinical stages (chronic individuals, both pre-HAART and under-HAART) and HIV-negative controls (n=20) were evaluated. Additionally, HIV-positive individuals that initiated HAART with >350CD4(+)T-cells/mm(3) were compared with those who initiated treatment with <350CD4(+)T-cells/mm(3)...
November 6, 2017: Infection, Genetics and Evolution
https://www.readbyqxmd.com/read/29103633/cd8-cd28-cd127-lo-cd39-regulatory-t-cell-expansion-a%C3%A2-new-possible-pathogenic-mechanism-for-hiv-infection
#3
Daniela Fenoglio, Chiara Dentone, Alessio Signori, Antonio Di Biagio, Alessia Parodi, Francesca Kalli, Giorgia Nasi, Monica Curto, Giovanni Cenderello, Pasqualina De Leo, Valentina Bartolacci, Giancarlo Orofino, Laura Ambra Nicolini, Lucia Taramasso, Edoardo Fiorillo, Valeria Orrù, Paolo Traverso, Bianca Bruzzone, Federico Ivaldi, Eugenio Mantia, Michele Guerra, Simone Negrini, Mauro Giacomini, Sanjay Bhagani, Gilberto Filaci
BACKGROUND: HIV-associated immunodeficiency is related to loss of CD4(+) T cells. This mechanism does not explain certain manifestations of HIV disease, such as immunodeficiency events in patients with greater than 500 CD4(+) T cells/μL. CD8(+)CD28(-)CD127(lo)CD39(+) T cells are regulatory T (Treg) lymphocytes that are highly concentrated within the tumor microenvironment and never analyzed in the circulation of HIV-infected patients. OBJECTIVES: We sought to analyze the frequency of CD8(+)CD28(-)CD127(lo)CD39(+) Treg cells in the circulation of HIV-infected patients...
October 28, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29031156/hiv-misdiagnosis-a-root-cause-analysis-leading-to-improvements-in-hiv-diagnosis-and-patient-care
#4
Raynell Lang, Carmen Charlton, Brenda Beckthold, Kiana Kadivar, Stephanie Lavoie, Debbie Caswell, Paul N Levett, Greg B Horsman, John Kim, M John Gill
BACKGROUND: Standard diagnostic testing for HIV infection has traditionally relied on a high sensitivity HIV antibody screening test using an enzyme-linked immunosorbent assay (ELISA) followed by a high specificity antibody confirmatory test such as a Western Blot. Recently several of the screening assays have been enhanced with an ability to identify p24 antigen thereby narrowing the diagnostic window. OBJECTIVES: To explore the implications of enhanced HIV screening methods that may be leading to HIV misdiagnoses...
October 9, 2017: Journal of Clinical Virology: the Official Publication of the Pan American Society for Clinical Virology
https://www.readbyqxmd.com/read/29021373/a-specialist-macaque-mhc-class-i-molecule-with-hla-b-27-like-peptide-binding-characteristics
#5
Natasja G de Groot, Corrine M C Heijmans, Arnoud H de Ru, George M C Janssen, Jan W Drijfhout, Nel Otting, Christelle Vangenot, Gaby G M Doxiadis, Frits Koning, Peter A van Veelen, Ronald E Bontrop
In different macaque species, the MHC A2*05 gene is present in abundance, and its gene products are characterized by low cell-surface expression and a highly conserved peptide-binding cleft. We have characterized the peptide-binding motif of Mamu-A2*05:01, and elucidated the binding capacity for virus-derived peptides. The macaque A2*05 allotype prefers the basic amino acid arginine at the second position of the peptide, and hydrophobic and polar amino acids at the C-terminal end. These preferences are shared with HLA-B*27 and Mamu-B*008, molecules shown to be involved in elite control in human HIV type 1 and macaque SIV infections, respectively...
October 11, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28938888/unique-binding-modes-for-the-broad-neutralizing-activity-of-single-chain-variable-fragments-scfv-targeting-cd4-induced-epitopes
#6
Kazuki Tanaka, Takeo Kuwata, Muntasir Alam, Gilad Kaplan, Shokichi Takahama, Kristel Paola Ramirez Valdez, Anna Roitburd-Berman, Jonathan M Gershoni, Shuzo Matsushita
BACKGROUND: The CD4-induced (CD4i) epitopes in gp120 includes the co-receptor binding site, which are formed and exposed after interaction with CD4. Monoclonal antibodies (mAbs) to the CD4i epitopes exhibit limited neutralizing activity because of restricted access to their epitopes. However, small fragment counterparts such as single-chain variable fragments (scFvs) have been reported to neutralize a broad range of viruses compared with the full-size IgG molecule. To identify the CD4i epitope site responsible for this broad neutralization we constructed three scFvs of anti-CD4i mAbs from a human immunodeficiency virus type 1 (HIV-1)-infected elite controller, and investigated the neutralization coverage and precise binding site in the CD4i epitopes...
September 22, 2017: Retrovirology
https://www.readbyqxmd.com/read/28902848/the-effect-of-hiv-infection-and-hcv-viremia-on-inflammatory-mediators-and-hepatic-injury-the-women-s-interagency-hiv-study
#7
Sheila M Keating, Jennifer L Dodge, Philip J Norris, John Heitman, Stephen J Gange, Audrey L French, Marshall J Glesby, Brian R Edlin, Patricia S Latham, Maria C Villacres, Ruth M Greenblatt, Marion G Peters
Hepatitis C virus infection induces inflammation and while it is believed that HIV co-infection enhances this response, HIV control may reduce inflammation and liver fibrosis in resolved or viremic HCV infection. Measurement of systemic biomarkers in co-infection could help define the mechanism of inflammation on fibrosis and determine if HIV control reduces liver pathology. A nested case-control study was performed to explore the relationship of systemic biomarkers of inflammation with liver fibrosis in HCV viremic and/or seropositive women with and without HIV infection...
2017: PloS One
https://www.readbyqxmd.com/read/28899396/transcriptomic-meta-analysis-identifies-gene-expression-characteristics-in-various-samples-of-hiv-infected-patients-with-nonprogressive-disease
#8
Le-Le Zhang, Zi-Ning Zhang, Xian Wu, Yong-Jun Jiang, Ya-Jing Fu, Hong Shang
BACKGROUND: A small proportion of HIV-infected patients remain clinically and/or immunologically stable for years, including elite controllers (ECs) who have undetectable viremia (<50 copies/ml) and long-term nonprogressors (LTNPs) who maintain normal CD4(+) T cell counts for prolonged periods (>10 years). However, the mechanism of nonprogression needs to be further resolved. In this study, a transcriptome meta-analysis was performed on nonprogressor and progressor microarray data to identify differential transcriptome pathways and potential biomarkers...
September 12, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28899104/therapeutic-vaccine-against-hiv-viral-variability-cytotoxic-t-lymphocyte-epitopes-and-genetics-of-patients
#9
Herve Fleury, Camille Tumiotto, Pantxika Bellecave, Patricia Recordon-Pinson
The scientific and medical community is seeking to cure HIV. Several pathways have been or are being explored including therapeutic vaccination. Viroimmunological studies on primary infection as well as on elite controllers have demonstrated the importance of the cytotoxic CD8 response and have mainly oriented research on vaccine constructs toward this type of response. The results of these trials are clearly not commensurate with the hope placed in them. Might there be one or more uncontrolled variables? The genetics of patients need to be taken into consideration, especially their human lymphocyte antigen (HLA) alleles...
October 12, 2017: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/28888341/hla-based-selection-of-epitopes-offers-a-potential-window-of-opportunity-for-vaccine-design-against-hiv
#10
REVIEW
Jagadish Chandrabose Sundaramurthi, Manickam Ashokkumar, Soumya Swaminathan, Luke Elizabeth Hanna
The pace of progression to AIDS after HIV infection varies from individual to individual. While some individuals develop AIDS quickly, others are protected from the onset of disease for more than a decade (elite controllers and long term non-progressors). The mechanisms of protection are not yet clearly understood, though various factors including host genetics, immune components and virus attenuation have been elucidated partly. The influence of HLA alleles on HIV-1 infection and disease outcome has been studied extensively...
September 6, 2017: Vaccine
https://www.readbyqxmd.com/read/28862291/trans-activation-response-element-rna-is-detectable-in-the-plasma-of-a-subset-of-aviremic-hiv-1-infected-patients
#11
Anžej Hladnik, Jana Ferdin, Katja Goričar, G Steven Deeks, M Boris Peterlin, Ana Plemenitaš, Dolžan Vita, Lenassi Metka
Determining the HIV-1 reservoir size in infected individuals is of great importance for improvement of their treatment. Plasma trans-activation response element (TAR) RNA has been suggested as one of the possible biomarkers. TAR RNA is produced during non-processive transcription in HIV-1 productively infected and latent T cells. Here, plasma samples and paired exosome samples of 55 subjects from the observational SCOPE cohort were analysed for the presence of TAR RNA. First, a PCR-based assay was optimized, which provided 100% specificity and 100% sensitivity in differentiating HIV-1 infected non-controllers from uninfected individuals...
September 2017: Acta Chimica Slovenica
https://www.readbyqxmd.com/read/28830571/anti-herv-k-hml-2-capsid-antibody-responses-in-hiv-elite-controllers
#12
Miguel de Mulder, Devi SenGupta, Steven G Deeks, Jeffrey N Martin, Christopher D Pilcher, Frederick M Hecht, Jonah B Sacha, Douglas F Nixon, Henri-Alexandre Michaud
BACKGROUND: Human endogenous retroviruses (HERVs) comprise approximately 8% of the human genome and while the majority are transcriptionally silent, the most recently integrated HERV, HERV-K (HML-2), remains active. During HIV infection, HERV-K (HML-2) specific mRNA transcripts and viral proteins can be detected. In this study, we aimed to understand the antibody response against HERV-K (HML-2) Gag in the context of HIV-1 infection. RESULTS: We developed an ELISA assay using either recombinant protein or 164 redundant "15mer" HERV-K (HML-2) Gag peptides to test sera for antibody reactivity...
August 22, 2017: Retrovirology
https://www.readbyqxmd.com/read/28799906/of-mice-macaques-and-men-broadly-neutralizing-antibody-immunotherapy-for-hiv-1
#13
REVIEW
Yoshiaki Nishimura, Malcolm A Martin
The neutralizing antibodies targeting the HIV-1 envelope protein have been a major focus for HIV therapy. Early studies with anti-HIV-1 neutralizing monoclonal antibodies (mAbs) administered to infected individuals showed some promise, as they resulted in transient reductions in plasma viremia in some recipients. However, resistant viral variants rapidly emerged. A major development during the past 6 to 7 years has been the isolation and characterization of highly potent and broadly neutralizing mAbs (bNAbs) from infected individuals known as "elite neutralizers...
August 9, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/28740260/richer-gut-microbiota-with-distinct-metabolic-profile-in-hiv-infected-elite-controllers
#14
Jan Vesterbacka, Javier Rivera, Kajsa Noyan, Mariona Parera, Ujjwal Neogi, Malu Calle, Roger Paredes, Anders Sönnerborg, Marc Noguera-Julian, Piotr Nowak
Gut microbiota dysbiosis features progressive HIV infection and is a potential target for intervention. Herein, we explored the microbiome of 16 elite controllers (EC), 32 antiretroviral therapy naive progressors and 16 HIV negative controls. We found that the number of observed genera and richness indices in fecal microbiota were significantly higher in EC versus naive. Genera Succinivibrio, Sutterella, Rhizobium, Delftia, Anaerofilum and Oscillospira were more abundant in EC, whereas Blautia and Anaerostipes were depleted...
July 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28720421/assessment-of-the-hiv-1-reservoir-in-cd4-regulatory-t-cells-by-a-droplet-digital-pcr-based-approach
#15
Gábor Artúr Dunay, Anastasia Solomatina, Silke Kummer, Anja Hüfner, Julia Katharina Bialek, Johanna Maria Eberhard, Eva Tolosa, Joachim Hauber, Julian Schulze Zur Wiesch
The relative contribution of regulatory T cells (Treg) as reservoir of HIV-1 in patients on chronic antiretroviral therapy is unclear to date. The aim of the current study was to assess the total HIV DNA burden and replication competent viral reservoir in Treg in comparison to central and effector memory cells (Tcm and Tem). Peripheral blood mononuclear cells were obtained from 10 HIV patients treated with antiretroviral therapy. Droplet Digital PCR (ddPCR) was used to quantify total HIV DNA loads in FACS-sorted CD4+ Treg (CD25+CD127lo) as compared to Tcm (CD45RO+CCR7+) and Tem (CD45RO+CCR7-)...
July 16, 2017: Virus Research
https://www.readbyqxmd.com/read/28701393/hiv-1-env-and-vpu-specific-antibody-dependent-cellular-cytotoxicity-responses-associated-with-elite-control-of-hiv
#16
Vijaya Madhavi, Bruce D Wines, Janaki Amin, Sean Emery, Ester Lopez, Anthony Kelleher, Rob J Center, P Mark Hogarth, Amy W Chung, Stephen J Kent, Ivan Stratov
Studying HIV-infected individuals who control HIV replication (elite controllers [ECs]) enables exploration of effective anti-HIV immunity. HIV Env-specific and non-Env-specific antibody-dependent cellular cytotoxicity (ADCC) may contribute to protection from progressive HIV infection, but the evidence is limited. We recruited 22 ECs and matched them with 44 viremic subjects. HIV Env- and Vpu-specific ADCC responses in sera were studied using a novel enzyme-linked immunosorbent assay (ELISA)-based dimeric recombinant soluble FcγRIIIa (rsFcγRIIIa)-binding assay, surface plasmon resonance, antibody-dependent natural killer (NK) cell activation assays, and ADCC-mediated killing assays...
September 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28695289/the-role-of-mhc-class-i-gene-products-in-siv-infection-of-macaques
#17
REVIEW
Zachary A Silver, David I Watkins
Human immunodeficiency virus (HIV) remains among the most significant public health threats worldwide. Despite three decades of research following the discovery of HIV, a preventive vaccine remains elusive. The study of HIV elite controllers has been crucial to elaborate the genetic and immunologic determinants that underlie control of HIV replication. Coordinated studies of elite control in humans have, however, been limited by variability among infecting viral strains, host genotype, and the uncertainty of the timing and route of infection...
August 2017: Immunogenetics
https://www.readbyqxmd.com/read/28672745/hiv-avidity-index-performance-using-a-modified-fourth-generation-immunoassay-to-detect-recent-hiv-infections
#18
Barbara Suligoi, Vincenza Regine, Mariangela Raimondo, Anna Rodella, Luigina Terlenghi, Arnaldo Caruso, Patrizia Bagnarelli, Maria Rosaria Capobianchi, Nadia Zanchetta, Valeria Ghisetti, Claudio Galli
BACKGROUND: Detecting recent HIV infections is important to evaluate incidence and monitor epidemic trends. We aimed to evaluate the diagnostic performance and accuracy of the avidity index (AI) for discriminating for recent HIV infections. METHODS: We collected serum samples from HIV-1 positive individuals: A) with known date of infection (midpoint in time between last HIV-negative and first HIV-positive test); B) infected for >1 year. Samples were divided into two aliquots: one diluted with phosphate buffered saline (PBS) and the other with 1 M guanidine...
October 26, 2017: Clinical Chemistry and Laboratory Medicine: CCLM
https://www.readbyqxmd.com/read/28671952/differences-in-serum-iga-responses-to-hiv-1-gp41-in-elite-controllers-compared-to-viral-suppressors-on-highly-active-antiretroviral-therapy
#19
COMPARATIVE STUDY
Rafiq Nabi, Zina Moldoveanu, Qing Wei, Elizabeth T Golub, Helen G Durkin, Ruth M Greenblatt, Betsy C Herold, Marek J Nowicki, Seble Kassaye, Michael W Cho, Abraham Pinter, Alan L Landay, Jiri Mestecky, Pamela A Kozlowski
Mechanisms responsible for natural control of human immunodeficiency type 1 (HIV) replication in elite controllers (EC) remain incompletely defined. To determine if EC generate high quality HIV-specific IgA responses, we used Western blotting to compare the specificities and frequencies of IgA to HIV antigens in serum of gender-, age- and race-matched EC and aviremic controllers (HC) and viremic noncontrollers (HN) on highly active antiretroviral therapy (HAART). Concentrations and avidity of IgA to HIV antigens were measured using ELISA or multiplex assays...
2017: PloS One
https://www.readbyqxmd.com/read/28658155/long-term-follow-up-of-elite-controllers-higher-risk-of-complications-with-hcv-coinfection-no-association-with-hiv-disease-progression
#20
Kristen A Stafford, Zahra Rikhtegaran Tehrani, Saman Saadat, Maryam Ebadi, Robert R Redfield, Mohammad M Sajadi
To estimate the effect of hepatitis C virus (HCV) coinfection on the development of complications and progression of human immunodeficiency virus (HIV) disease among HIV-infected elite controllers.Single-center retrospective cohort. Kaplan-Meier methods, prevalence ratios, and Cox proportional-hazards models were used.In all, 55 HIV-infected elite controllers were included in this study. Among them, 45% were HIV/HCV coinfected and 55% were HIV mono-infected. Median follow-up time for the cohort was 11 years...
June 2017: Medicine (Baltimore)
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