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HIV Elite Controllers

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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
#1
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
#2
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-ctl-epitopes-and-genetics-of-patients
#3
Herve J 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. Viro-immunological 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 towards 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 HLA alleles...
September 13, 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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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...
July 10, 2017: Immunogenetics
https://www.readbyqxmd.com/read/28672745/hiv-avidity-index-performance-using-a-modified-fourth-generation-immunoassay-to-detect-recent-hiv-infections
#12
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...
June 24, 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
#13
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
#14
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)
https://www.readbyqxmd.com/read/28656019/characterization-of-elite-suppressors-cell-associated-hiv-1-mrna-at-baseline-and-with-t-cell-activation%C3%A2-%C3%A2
#15
Christopher W Pohlmyer, C Korin Bullen, Alyssa R Martin, Gregory M Laird, Stanley U Chioma, Victoria E K Walker-Sperling, Joel N Blankson
Objective: Elite Controllers or Suppressors (ES) are patients who control HIV replication without antiretroviral therapy. In this study, we compared baseline and inducible HIV-1 mRNA levels in CD4+ T cells from ES and chronic progressors (CPs) receiving suppressive antiretroviral therapy. Methods: We quantified basal levels of cell associated HIV-1 mRNA in CD4+ T cells isolated from CPs and ES. Additionally, we measured the fold upregulation of intracellular HIV-mRNA after stimulation of CD4+ T cells with phorbol 12-myristate 13-acetate (PMA) and ionomycin, and quantified the amount of HIV-mRNA levels released into culture supernatant...
June 2017: Yale Journal of Biology and Medicine
https://www.readbyqxmd.com/read/28656011/mechanisms-of-virologic-control-and-clinical-characteristics-of-hiv-elite-viremic-controllers
#16
REVIEW
Elena Gonzalo-Gil, Uchenna Ikediobi, Richard E Sutton
Human immunodeficiency virus type 1 (HIV-1) disease is pandemic, with approximately 36 million infected individuals world-wide. For the vast majority of these individuals, untreated HIV eventually causes CD4+ T cell depletion and profound immunodeficiency, resulting in morbidity and mortality. But for a remarkable few (0.2 to 0.5 percent), termed elite controllers (ECs), viral loads (VLs) remain suppressed to undetectable levels (< 50 copies/ml) and peripheral CD4+ T cell counts remain high (200 to 1000/μl), all in the absence of antiretroviral therapy (ART)...
June 2017: Yale Journal of Biology and Medicine
https://www.readbyqxmd.com/read/28650937/weak-hiv-antibody-responses-in-perinatally-infected-young-adults
#17
Allison R Kirkpatrick, Aylin B Unsal, Joel N Blankson, Richard D Moore, Thomas C Quinn, Colleen Hadigan, Oliver Laeyendecker
We compared the antibody response to HIV using two serologic cross-sectional incidence assays in adults with perinatally-acquired HIV, to elite controllers and individuals exposed to antiretroviral therapy who were all infected as adults. Low antibody responses were seen more frequently in adults with perinatally-acquired HIV, both overall and when stratified by viral suppression status.
June 23, 2017: Pediatric Infectious Disease Journal
https://www.readbyqxmd.com/read/28615199/impaired-downregulation-of-nkg2d-ligands-by-nef-proteins-from-elite-controllers-sensitizes-hiv-1-infected-cells-to-antibody-dependent-cellular-cytotoxicity
#18
Nirmin Alsahafi, Jonathan Richard, Jérémie Prévost, Mathieu Coutu, Nathalie Brassard, Matthew S Parsons, Daniel E Kaufmann, Mark Brockman, Andrés Finzi
HIV-1 Nef clones isolated from a rare subset of HIV-1-infected elite controllers (EC), with the ability to suppress viral load to undetectable levels in the absence of antiretroviral therapy, are unable to fully downregulate CD4 from the plasma membrane of CD4(+) T cells. Residual CD4 left at the plasma membrane allows Env-CD4 interaction, which leads to increased exposure of Env CD4-induced epitopes and increases susceptibility of infected cells to antibody-dependent cellular cytotoxicity (ADCC). ADCC is mediated largely by natural killer (NK) cells, which control their activation status through the cumulative signals received through activating and inhibitory receptors...
August 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28615147/hiv-specific-b-cell-frequency-correlates-with-neutralization-breadth-in-patients-naturally-controlling-hiv-infection
#19
Angeline Rouers, Jéromine Klingler, Bin Su, Assia Samri, Géraldine Laumond, Sophie Even, Véronique Avettand-Fenoel, Clemence Richetta, Nicodème Paul, Faroudy Boufassa, Laurent Hocqueloux, Hugo Mouquet, Christine Rouzioux, Olivier Lambotte, Brigitte Autran, Stéphanie Graff-Dubois, Christiane Moog, Arnaud Moris
HIV-specific broadly neutralizing antibodies (bnAbs) have been isolated from patients with high viremia but also from HIV controllers that repress HIV-1 replication. In these elite controllers (ECs), multiple parameters contribute to viral suppression, including genetic factors and immune responses. Defining the immune correlates associated with the generation of bnAbs may help in designing efficient immunotherapies. In this study, in ECs either positive or negative for the HLA-B*57 protective allele, in treated HIV-infected and HIV-negative individuals, we characterized memory B cell compartments and HIV-specific memory B cells responses using flow cytometry and ELISPOT...
July 2017: EBioMedicine
https://www.readbyqxmd.com/read/28604502/the-association-of-hiv-1-gag-specific-igg-antibodies-with-natural-control-of-hiv-1-infection-in-individuals-not-carrying-hla-b-57-01-is-only-observed-in-viremic-controllers
#20
M Christian Tjiam, Mazmah A Morshidi, Lucy Sariputra, Jeffrey N Martin, Steven G Deeks, Dino Tan, Silvia Lee, Sonia Fernandez, Martyn A French
To expand upon our previous observation that HIV-1 Gag-specific IgG antibodies were highest in HIV controllers not carrying HLA-B*57:01, we analysed these antibodies in a larger cohort of viremic controllers (VCs) or elite controllers (ECs) considering carriage of 'protective' HLA-B alleles. HIV-1 p24-specific IgG1 and IgG2 antibodies were higher only in HLA-B*57:01 VCs but there were no differences in ECs. Associations of HIV-1 gp140-specific IgG antibodies with HLA-B*57:01 carriage were inconsistent amongst VCs and ECs...
June 9, 2017: Journal of Acquired Immune Deficiency Syndromes: JAIDS
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