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HIV Elite Controllers

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https://www.readbyqxmd.com/read/28799906/of-mice-macaques-and-men-broadly-neutralizing-antibody-immunotherapy-for-hiv-1
#1
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
#2
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
#3
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 and one HIV elite controller. Droplet Digital PCR (ddPCR) was used to quantify total HIV DNA loads in FACS sorted CD4+ Treg (CD25+CD127lo) as compared with Tcm (CD45RO+CCR7+) and Tem (CD45RO+CCR7-)...
July 15, 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
#4
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) enable exploration of effective anti-HIV immunity. HIV Env- 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 were studied in sera using a novel ELISA-based dimeric recombinant soluble (rs) FcγRIIIa-binding assay, surface plasmon resonance, antibody-dependent natural killer (NK) cell activation assays and ADCC-mediated killing assays...
July 12, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28695289/the-role-of-mhc-class-i-gene-products-in-siv-infection-of-macaques
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
https://www.readbyqxmd.com/read/28498985/hiv-antibodies-detect-hiv-persistence-and-low-level-viral-replication
#15
Sheila M Keating, Christopher D Pilcher, Vivek Jain, Mila Lebedeva, Dylan Hampton, Mohamed Abdel-Mohsen, Xutao Deng, Gary Murphy, Alex Welte, Shelley N Facente, Frederick Hecht, Steven G Deeks, Satish K Pillai, Michael P Busch
BACKGROUND: HIV antibodies are generated and maintained by ongoing systemic expression of HIV antigen. We investigated whether HIV antibody responses as measured by high-throughput quantitative and qualitative assays could be used to indirectly measure persistent HIV replication in individuals on antiretroviral therapy (ART). METHODS: HIV antibody measurements were made over time on and off suppressive ART and were compared to measures of HIV reservoir size and expression of anti-viral restriction factors...
May 11, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28497113/toward-a-cure-does-host-immunity-play-a-role
#16
Jielin Zhang, Clyde S Crumpacker
Three decades of research on human immunodeficiency virus (HIV) and AIDS reveal that the human body has developed through evolution a genome immune system embodying epigenetic regulation against pathogenic nucleic acid invasion. In HIV infection, this epigenetic regulation plays a cardinal role in HIV RNA production that silences HIV transcription at a molecular (RNA) level, controls viral load at a cellular (biological) level, and governs the viremic stage of AIDS at the clinical (patient) level. Even though the human genome is largely similar among humans and HIV is a single viral species, human hosts show significant differences in viral RNA levels, ranging from cell to organ to individual and expressed as elite controllers, posttreatment controllers, and patients with AIDS...
March 2017: MSphere
https://www.readbyqxmd.com/read/28468877/preservation-of-peripheral-t-follicular-helper-cell-function-in-hiv-controllers
#17
Supranee Buranapraditkun, Franco Pissani, Jeffrey E Teigler, Bruce T Schultz, Galit Alter, Mary Marovich, Merlin L Robb, Michael A Eller, Jeff Martin, Steven Deeks, Nelson L Michael, Hendrik Streeck
The maturation process of high-affinity antibodies is a result of intricate interactions between B cells and follicular helper T (Tfh) cells occurring in lymphoid germinal centers. HIV infection induces significant chronic immune activation, phenotypic skewing, and inflammation driven by years of continuous viral replication. High levels of viremia as well as immune activation and dysfunction have been demonstrated to have a perturbing impact on the B cell memory compartment and contribute to B cell exhaustion...
July 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28467486/the-effect-of-ingenol-b-on-the-suppressive-capacity-of-elite-suppressor-hiv-specific-cd8-t-cells
#18
Abena K Kwaa, Kennedy Goldsborough, Victoria E Walker-Sperling, Luiz F Pianowski, Lucio Gama, Joel N Blankson
BACKGROUND: Some latency-reversing agents (LRAs) inhibit HIV-specific CD8+ T cell responses. In a prior study of protein kinase C (PKC) agonists, we found that bryostatin-1 inhibited elite controller/suppressor (ES) CD8+ T cell suppressive activity whereas prostratin had no effect. Ingenol-B is another PKC agonist with potent LRA activity both by itself and in combination with the bromodomain inhibitor JQ1; however its effect on CD8+ T cell mediated control of HIV-1 replication is unknown...
2017: PloS One
https://www.readbyqxmd.com/read/28464889/highly-divergent-patterns-of-genetic-diversity-and-evolution-in-proviral-quasispecies-from-hiv-controllers
#19
Suwellen S D de Azevedo, Diogo Gama Caetano, Fernanda H Côrtes, Sylvia L M Teixeira, Karina Dos Santos Silva, Brenda Hoagland, Beatriz Grinsztejn, Valdilea G Veloso, Mariza G Morgado, Gonzalo Bello
BACKGROUND: Ongoing intra-host HIV-1 evolution has been shown in individuals that naturally suppress the viremia to low levels (HIV controllers) by the analysis of the RNA in plasma compartment. Detection of evolution at the DNA proviral compartment in HIV controllers, however, has been more challenging and the precise correlation between the systemic viral suppression level and rate of reservoir's reseeding in those individuals is not fully understood. In this sense, we examined the proviral DNA quasispecies by single genome amplification of the env gene in a cohort of 23 HIV controllers from Brazil, divided in three groups, according to the level of systemic viral suppression: (1) elite controllers with persistent undetectable viral load (PEC, n = 6); (2) elite controllers with occasional episodes of transient (51-400 copies/mL) viremia (EEC, n = 7); and (3) viremic controllers with persistent low-level (80-2000 copies/mL) viremia (VC, n = 10)...
May 2, 2017: Retrovirology
https://www.readbyqxmd.com/read/28428094/cxcr6-gene-characterization-in-two-ethnically-distinct-south-african-populations-and-association-with-viraemic-disease-control-in-hiv-1-infected-black-south-african-individuals
#20
Anabela C P Picton, Maria Paximadis, Richard E Chaisson, Neil A Martinson, Caroline T Tiemessen
CXCR6 genetic variation was described for HIV-1-uninfected black (n=41) and Caucasian (n=40) South Africans. We also investigated the CXCR6 rs2234358 and rs2234355 single nucleotide polymorphisms in HIV-1 disease control in 124 HIV-1-infected drug-naïve black individuals [elite controllers (n=11), viraemic controllers (VCs, n=30), high viral load long-term nonprogressors (HVL LTNPs, n=11) and progressors (n=72)] compared to healthy controls (HCs; n=232). The rs2234358-T allele was underrepresented in VCs (40...
July 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
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