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"Elite control"

Jesús Rodríguez-Muñoz, Santiago Moreno
The disadvantages of the long-term administration of antiretroviral therapy as well as the huge number of affected persons have placed the cure of HIV as a primary goal of Public Health. HIV may persist in the organism by at least four mechanisms: a latently infected cellular reservoir, the persistent replication of HIV in spite of ART, anatomic sanctuaries, and the immune dysfunction. Several strategies directed against these mechanisms have been developed. With all this, a complete eradication of HIV has been achieved in a patient using the transplantation of haemopoietic stem cells that were resistant to HIV-infection, and there are examples of functional cure either spontaneously (elite controllers) or after antiretroviral therapy (post-treatment controllers)...
March 3, 2018: Enfermedades Infecciosas y Microbiología Clínica
Isabelle Poizot-Martin, Hélène Laroche, Carla E Cano, Corinne Nicolino-Brunet, Olivia Zaegel-Faucher, Sylvie Bregigeon, Catherine Tamalet, Françoise Dignat-George
No abstract text is available yet for this article.
March 13, 2018: AIDS
José M Benito, María C Ortiz, Agathe León, Luis A Sarabia, José M Ligos, María Montoya, Marcial Garcia, Ezequiel Ruiz-Mateos, Rosario Palacios, Alfonso Cabello, Clara Restrepo, Carmen Rodriguez, Jorge Del Romero, Manuel Leal, María A Muñoz-Fernández, José Alcamí, Felipe García, Miguel Górgolas, Norma Rallón
BACKGROUND: Despite long-lasting HIV replication control, a significant proportion of elite controller (EC) patients may experience CD4 T-cell loss. Discovering perturbations in immunological parameters could help our understanding of the mechanisms that may be operating in those patients experiencing loss of immunological control. METHODS: A case-control study was performed to evaluate if alterations in different T-cell homeostatic parameters can predict CD4 T-cell loss in ECs by comparing data from EC patients showing significant CD4 decline (cases) and EC patients showing stable CD4 counts (controls)...
February 28, 2018: BMC Medicine
Ana Flávia Pina, Vanessa Terezinha Gubert de Matos, Camila Mareti Bonin, Márcia Maria Ferrairo Janini Dal Fabbro, Inês Aparecida Tozetti
The HIV-1 initial viral infection may present diverse clinical and laboratory course and lead to rapid, intermediate, or long-term progression. Among the group of non-progressors, the elite controllers are those who control the infection most effectively, in the absence of antiretroviral therapy (ART). In this paper, the TH1, TH2 and TH17 cytokines profiles are described, as well as clinical and laboratory aspects of an HIV-infected patient with undetectable viral load without ART. Production of IL-6, IL-10, TNF-α, IFN-γ, and IL-17 was detected; in contrast, no IL-2 or IL-4 was identified...
February 21, 2018: Brazilian Journal of Infectious Diseases
Kajsa Noyan, Son Nguyen, Michael R Betts, Anders Sönnerborg, Marcus Buggert
Human immunodeficiency virus type-1 (HIV-1) elite controllers (ELCs) represent a unique population that control viral replication in the absence of antiretroviral therapy (cART). It is well established that expression of multiple inhibitory receptors on CD8+ T cells is associated with HIV-1 disease progression. However, whether reduced co-expression of inhibitory receptors on CD4+ T cells is linked to natural viral control and slow HIV-1 disease progression remains undefined. Here, we report on the expression pattern of numerous measurable inhibitory receptors, associated with T cell exhaustion (programmed cell death-1, CTLA-4, and TIGIT), on different CD4+ T cell memory populations in ELCs and HIV-infected subjects with or without long-term cART...
2018: Frontiers in Immunology
Enrique Martin-Gayo, Michael B Cole, Kellie E Kolb, Zhengyu Ouyang, Jacqueline Cronin, Samuel W Kazer, Jose Ordovas-Montanes, Mathias Lichterfeld, Bruce D Walker, Nir Yosef, Alex K Shalek, Xu G Yu
BACKGROUND: Human immunity relies on the coordinated responses of many cellular subsets and functional states. Inter-individual variations in cellular composition and communication could thus potentially alter host protection. Here, we explore this hypothesis by applying single-cell RNA-sequencing to examine viral responses among the dendritic cells (DCs) of three elite controllers (ECs) of HIV-1 infection. RESULTS: To overcome the potentially confounding effects of donor-to-donor variability, we present a generally applicable computational framework for identifying reproducible patterns in gene expression across donors who share a unifying classification...
January 29, 2018: Genome Biology
Yumna Moosa, Ramla F Tanko, Veron Ramsuran, Ravesh Singh, Mashudu Madzivhandila, Nonhlanhla Yende-Zuma, Melissa-Rose Abrahams, Philippe Selhorst, Kamini Gounder, Penny L Moore, Carolyn Williamson, Salim S Abdool Karim, Nigel J Garrett, Wendy A Burgers
BACKGROUND: The majority of people living with HIV require antiretroviral therapy (ART) for controlling viral replication, however there are rare HIV controllers who spontaneously and durably control HIV in the absence of treatment. Understanding what mediates viral control in these individuals has provided us with insights into the immune mechanisms that may be important to induce for a vaccine or functional cure for HIV. To date, few African elite controllers from high incidence settings have been described...
January 25, 2018: BMC Infectious Diseases
Gabriela M Webb, Shengbin Li, Gwantwa Mwakalundwa, Joy M Folkvord, Justin M Greene, Jason S Reed, Jeffery J Stanton, Alfred W Legasse, Theodore Hobbs, Lauren D Martin, Byung S Park, James B Whitney, Emily K Jeng, Hing C Wong, Douglas F Nixon, R Brad Jones, Elizabeth Connick, Pamela J Skinner, Jonah B Sacha
Sequestering of latent HIV in follicular helper T cells within B-cell follicles that largely exclude cytotoxic T cells is a major barrier to cellular immune-based approaches to eradicate HIV. Here, we show that the clinical-grade human interleukin-15 (IL-15) superagonist ALT-803 activates and redirects simian immunodeficiency virus (SIV)-specific CD8+ T cells from the peripheral blood into B-cell follicles. In agreement with the increased trafficking of SIV-specific cytotoxic T cells to sites of cryptic viral replication, lymph nodes of elite controlling macaques contained fewer cells expressing SIV RNA or harboring SIV DNA post-ALT-803 treatment...
January 23, 2018: Blood Advances
Jana Ferdin, Katja Goričar, Vita Dolžan, Ana Plemenitaš, Jeffrey N Martin, Boris M Peterlin, Steven G Deeks, Metka Lenassi
OBJECTIVE: To address the role of translationally active HIV reservoir in chronic inflammation and non-AIDS related disorders, we first need a simple and accurate assay to evaluate viral protein expression in virally suppressed subjects. DESIGN: We optimized an HIV Nef enzyme-linked immunosorbent assay (ELISA) and used it to quantify plasma Nef levels as an indicator of the leaky HIV reservoir in an HIV-infected cohort. METHODS: This study accessed 134 plasma samples from a well-characterized cohort study of HIV-infected and uninfected adults in San Francisco (the SCOPE cohort)...
2018: PloS One
Jacqui Brener, Astrid Gall, Jacob Hurst, Rebecca Batorsky, Nora Lavandier, Fabian Chen, Anne Edwards, Chrissy Bolton, Reena Dsouza, Todd Allen, Oliver G Pybus, Paul Kellam, Philippa C Matthews, Philip J R Goulder
BACKGROUND: The factors determining differential HIV disease outcome among individuals expressing protective HLA alleles such as HLA-B*27:05 and HLA-B*57:01 remain unknown. We here analyse two HIV-infected subjects expressing both HLA-B*27:05 and HLA-B*57:01. One subject maintained low-to-undetectable viral loads for more than a decade of follow up. The other progressed to AIDS in < 3 years. RESULTS: The rapid progressor was the recipient within a known transmission pair, enabling virus sequences to be tracked from transmission...
January 16, 2018: Retrovirology
José M Benito, Julia Hillung, Clara Restrepo, José M Cuevas, Agathe León, Ezequiel Ruiz-Mateos, Rosario Palacios-Muñoz, Miguel Górgolas, Rafael Sanjuán, Norma Rallón
Background APOBEC3H (A3H) gene presents variation at 2 positions (rs139297 and rs79323350) leading to a non-functional protein. So far, there is no information on the role played by A3H in spontaneous control of HIV. The aim of this study was to evaluate the A3H polymorphisms distribution in a well-characterized group of Elite Controller (EC) subjects. Methods We analyzed the genotype distribution of two different SNPs (rs139297 and rs79323350) of A3H in 30 EC patients and compared with 11 non-controller (NC) HIV patients...
2018: International Journal of Medical Sciences
M Bendenoun, A Samri, V Avettand-Fènoël, S Cardinaud, B Descours, G Carcelain, M-C Mazeron, J-F Bergmann, A Urrutia, A Moris, C Rouzioux, F Simon, P Andre, M Pocard, X Dray, T Mourez, V Vieillard, B Autran, F Barin, P Sellier
BACKGROUND: We describe a homosexual man who strongly controlled HIV-1 for ten years despite lack of protective genetic background. METHODS: HIV-1 DNA was measured in blood and other tissues. Cell susceptibility was evaluated with various strains. HIV-1-specific (CD4 and CD8 activation markers and immune check points) and NK cells responses were assessed; KIRs haplotypes and HLA alleles were determined. FINDINGS: Two HIV-1 RNA copies/mL of plasma were detected in 2009, using an ultra-sensitive assay...
December 7, 2017: EBioMedicine
María Pernas, Laura Tarancón-Diez, Esther Rodríguez-Gallego, Josep Gómez, Julia G Prado, Concepción Casado, Beatriz Dominguez-Molina, Isabel Olivares, Maite Coiras, Agathe León, Carmen Rodriguez, Jose Miguel Benito, Norma Rallón, Montserrat Plana, Onofre Martinez-Madrid, Marta Dapena, Jose Antonio Iribarren, Jorge Del Romero, Felipe García, José Alcamí, M Ángeles Muñoz-Fernández, Francisco Vidal, Manuel Leal, Cecilio Lopez-Galindez, Ezequiel Ruiz-Mateos
HIV-1 elite controllers (EC) maintain undetectable viral load (VL) in the absence of antiretroviral treatment. However, these subjects have heterogeneous clinical outcomes including a proportion loosing HIV-1 control over time. In this work we compared, in a longitudinal design, transient EC, analyzed before and after the loss of virological control, versus persistent EC. The aim was to identify factors leading to the loss of natural virological control of HIV-1-infection with a longitudinal retrospective study design...
December 6, 2017: Journal of Virology
Jucelia Stadinicki Dos Santos, Sergio Monteiro de Almeida, Guilherme Silveira Ferreira, Juliano Bordignon, Sylvia Lopes Maia Teixeira, Alberto Cardoso Martins Lima, Sonia Mara Raboni
BACKGROUND: HIV-1+ long-term nonprogressors (LTNPs) maintain natural control of viral infection. This study sought to identify and characterize HIV- LTNPs series case, regarding the presence of possible host factors that may be associated with this status. METHODS: We evaluated the plasma levels of IP-10/IL-8 chemokines, HLA-B alleles, and IL28B rs12979860 polymorphism in 24 LTNPs who presented with infection by different clades of HIV-1. RESULTS: IL-8 chemokine was significantly higher in progressors than in LTNPs, but there was no difference between the LTNP subgroups...
2017: Current HIV Research
Marcial García, Miguel Górgolas, Alfonso Cabello, Vicente Estrada, José Manuel Ligos, Manuel Fernández-Guerrero, Carlos Barros, Juan Carlos López-Bernaldo, Francisco Javier De La Hera, María Montoya, José Miguel Benito, Norma Rallón
HIV latency is the main barrier to HIV eradication. Peripheral T follicular helper (pTfh) cells have a prominent role in HIV persistence. Herein, we analyzed the HIV reservoir size within memory CD4+ T-cell subsets in patients with HIV replication control. Twenty HIV-infected patients with suppressed HIV replication were included, with 10 elite controllers (EC) and 10 treated (TX) individuals. The HIV reservoir size was analyzed in resting memory CD4+ T-cells (Trm), pTfh, and non-pTfh cells using an ultrasensitive digital-droplet-PCR assay...
December 1, 2017: Scientific Reports
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...
January 2018: Current Opinion in HIV and AIDS
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/mm3 were compared with those who initiated treatment with <350CD4+ T-cells/mm3 ...
January 2018: Infection, Genetics and Evolution
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- CD127lo 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- CD127lo CD39+ Treg cells in the circulation of HIV-infected patients...
October 28, 2017: Journal of Allergy and Clinical Immunology
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
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...
November 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
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