Genetic and Immunologic Heterogeneity among Persons Who Control HIV Infection in the Absence of Therapy
Florencia Pereyra,Marylyn M. Addo,Daniel Kaufmann,Yang Liu,Toshiyuki Miura,Almas Rathod,Brett Baker,Alicja Trocha,Alicja Trocha,Rachel Rosenberg,Elizabeth W Mackey,Peggy Ueda,Zhigang Lu,Daniel E. Cohen,Terri Wrin,Christos J. Petropoulos,Eric S. Rosenberg,Bruce D. Walker,Bruce D. Walker +18 more
TLDR
Even low-level viremia among HIV controllers was associated with measurable T cell dysfunction, which has implications for current prophylactic vaccine strategies.Abstract:
Background Spontaneous control of human immunodeficiency virus (HIV) infection has been documented in a minority of HIV-infected individuals. The mechanisms behind this outcome remain largely unknown, and a better understanding of them will likely influence future vaccine strategies. Methods HIV-specific T cell and antibody responses as well as host genetics were examined in untreated HIV-infected patients who maintain comparatively low plasma HIV RNA levels (hereafter, controllers), including those with levels of 10,000 copies/mL (chronic progressors, n = 30). Results CD8+ T cells from both controller groups preferentially target Gag over other proteins in the context of diverse HLA class I alleles, whereas responses are more broadly distributed in persons with progressive infection. Elite controllers represent a distinct group of individuals who have significantly more CD4 and CD8 T cells that secrete interferon-gamma and interleukin-2 and lower levels of HIV-neutralizing antibodies. Individual responses were quite heterogeneous, and none of the parameters evaluated was uniquely associated with the ability to control viremia. Conclusions Elite controllers are a distinct group, even when compared to persons with low level viremia, but they exhibit marked genetic and immunologic heterogeneity. Even low-level viremia among HIV controllers was associated with measurable T cell dysfunction, which has implications for current prophylactic vaccine strategies.read more
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Efficacy assessment of a cell-mediated immunity HIV-1 vaccine (the Step Study): a double-blind, randomised, placebo-controlled, test-of-concept trial.
Susan Buchbinder,Devan V. Mehrotra,Ann Duerr,Daniel W. Fitzgerald,Robin Mogg,David Li,Peter B. Gilbert,Javier R. Lama,Michael Marmor,Carlos del Rio,M. Juliana McElrath,Danilo R. Casimiro,Keith Gottesdiener,Chodakewitz Jeffrey A,Lawrence Corey,Michael N. Robertson +15 more
TL;DR: This cell-mediated immunity vaccine did not prevent HIV-1 infection or reduce early viral level and Mechanisms for insufficient efficacy of the vaccine and the increased HIV- 1 infection rates in subgroups of vaccine recipients are being explored.
Journal ArticleDOI
The major genetic determinants of HIV-1 control affect HLA class I peptide presentation
Florencia Pereyra,Xiaoming Jia,Paul J. McLaren,Amalio Telenti,de Bakker Pi,Bruce D. Walker,Stephan Ripke,Chanson J. Brumme,Sara L. Pulit,Mary Carrington,Carl M. Kadie,Jonathan M. Carlson,David E. Heckerman,Graham Rr,Robert M. Plenge,Steven G. Deeks,Gianniny L,Gabriel Crawford,Jean C. Sullivan,Elena Gonzalez,Davies L,Amy L. Camargo,Jamie Moore,Beattie N,Soumi Gupta,Crenshaw A,N P Burtt,Candace Guiducci,Namrata Gupta,Gao X,Qi Y,Yuko Yuki,Alicja Piechocka-Trocha,Emily Cutrell,Rachel Rosenberg,Kristin Moss,Lemay P,Jacqueline G. O'Leary,Schaefer T,Verma P,I Tóth,Brian L. Block,Brett Baker,Alissa C. Rothchild,Lian J,Jacqueline Proudfoot,Donna Marie Alvino,Seanna Vine,Marylyn M. Addo,Todd M. Allen,Marcus Altfeld,Matthew R. Henn,Le Gall S,Hendrik Streeck,David W. Haas,Daniel R. Kuritzkes,Gregory K. Robbins,Robert W. Shafer,Roy M. Gulick,Cecilia M. Shikuma,Richard Haubrich,Sharon A. Riddler,Paul E. Sax,Eric S. Daar,Heather J. Ribaudo,Brian K. Agan,Agarwal S,Ryan Ahern,Allen Bl,Altidor S,Altschuler El,Ambardar S,Kathryn Anastos,Brenna L. Anderson,Anderson,Andrady U,Antoniskis D,David R. Bangsberg,Barbaro D,Barrie W,Bartczak J,Barton S,Basden P,Nesli Basgoz,Suzane Bazner,Nicholas Bellos,Benson Am,Judith Berger,Bernard Nf,Bernard Am,Christopher E. Birch,Bodner Sj,Robert K. Bolan,Boudreaux Et,Meg Bradley,Braun Jf,Brndjar Je,Stephen J. Brown,Brown K,Sheldon T. Brown,Burack J,Bush Lm,Cafaro,Campbell O,Justin Campbell,Carlson Rh,Carmichael Jk,Casey Kk,Cavacuiti C,Celestin G,Stephen T. Chambers,Chez N,Lisa M. Chirch,Cimoch Pj,Daniel E. Cohen,Cohn Le,Brian Conway,David A. Cooper,Cornelson B,Cox Dt,Cristofano Mv,Cuchural G,Julie Czartoski,Dahman Jm,Jennifer S. Daly,Benjamin T. Davis,Kenneth L. Davis,Davod Sm,Edwin DeJesus,Craig A. Dietz,Dunham E,Dunn Me,Todd B. Ellerin,J. J. Eron,John Fangman,Farel Ce,Ferlazzo H,Sarah Fidler,Fleenor-Ford A,Frankel R,Kenneth A. Freedberg,French Nk,Jonathan D. Fuchs,Jon Fuller,Gaberman J,Joel E. Gallant,Rajesh T. Gandhi,Garcia E,Garmon D,J. Gathe,Gaultier Cr,Gebre W,Gilman Fd,Gilson I,Paul A. Goepfert,M. S. Gottlieb,Claudia Goulston,Groger Rk,Gurley Td,Haber S,Hardwicke R,W D Hardy,P. R. Harrigan,Trevor Hawkins,Sonya L. Heath,Frederick Hecht,Henry Wk,Hladek M,Hoffman Rp,James Horton,Hsu Rk,Gregory D Huhn,Peter W. Hunt,Hupert Mj,Illeman Ml,Hans Jaeger,Robert M. Jellinger,Mina John,Jennifer Johnson,Kristin Johnson,Johnson H,Kevin M. Johnson,Joly J,Wilbert C. Jordan,Carol A. Kauffman,Khanlou H,Killian Rk,Arthur Y. Kim,Kim Dd,Kinder Ca,Kirchner Jt,Laura Kogelman,Erna M. Kojic,Korthuis Pt,Kurisu W,Douglas S. Kwon,Melissa Lamar,Harry Lampiris,Lanzafame M,Michael M. Lederman,Lee Dm,Lee Jm,Lee Mj,Lee Et,Lemoine J,Jay A. Levy,Josep M. Llibre,Liguori Ma,Susan J. Little,Anne Y. Liu,Lopez Aj,Mona R. Loutfy,Loy D,Mohammed Dy,Man A,Michael K. Mansour,Vincent C. Marconi,Martin Markowitz,R. Marques,Jeffrey N. Martin,Hal Martin,Kenneth H. Mayer,MJ McElrath,McGhee Ta,Barbara H. McGovern,Katherine McGowan,McIntyre D,Mcleod Gx,Menezes P,Mesa G,Craig E. Metroka,Dirk Meyer-Olson,Miller Ao,Montgomery K,Karam Mounzer,Ellen H. Nagami,Nagin I,Nahass Rg,Nelson Mo,Nielsen C,Norene Dl,David H. O’Connor,Bisola O. Ojikutu,Jason F. Okulicz,Oladehin Oo,Oldfield Ec rd,Susan Olender,Mario A. Ostrowski,William F. Owen,Pae E,Parsonnet J,Pavlatos Am,Perlmutter Am,Pierce Mn,Pincus Jm,Pisani L,Price Lj,Laurie A. Proia,Prokesch Rc,Pujet Hc,Moti Ramgopal,Almas Rathod,Rausch M,Ravishankar J,Frank S. Rhame,Richards Cs,Douglas D. Richman,Rodes B,Rodriguez M,Rose Rc rd,Eric S. Rosenberg,Daniel I. Rosenthal,Ross Pe,Diana Rubin,Rumbaugh E,Saenz L,Michelle R Salvaggio,Sanchez Wc,Sanjana Vm,Steven Santiago,Schmidt W,Hanneke Schuitemaker,Sestak Pm,P. Shalit,Shay W,Shirvani Vn,Silebi Vi,Sizemore Jm,Paul R. Skolnik,Marcia Sokol-Anderson,James M. Sosman,Stabile P,Jack T. Stapleton,Starrett S,Stein F,Hans-Jürgen Stellbrink,Sterman Fl,Valerie E. Stone,David Stone,Giuseppe Tambussi,Randy Taplitz,Ellen Tedaldi,Theisen W,Ramon A. Torres,Tosiello L,Cécile Tremblay,Tribble Ma,Trinh Pd,Tsao A,Ueda P,Vaccaro A,Valadas E,Vanig Tj,Vecino I,Vega Vm,Veikley W,Wade Bh,Walworth C,Wanidworanun C,Doug Ward,Warner Da,Rainer Weber,Daniel P. Webster,Weis S,David Wheeler,D. White,Edmund Wilkins,Alan Winston,Wlodaver Cg,van't Wout A,Wright Dp,Otto O. Yang,Yurdin Dl,Zabukovic Bw,Kimon C. Zachary,Zeeman B,Zhao M +336 more
TL;DR: Differences in binding to viral peptide antigens by HLA may be the major factors underlying genetic differences between HIV controllers and progressors, and genome-wide association results implicate the nature of the HLA–viral peptide interaction as the major factor modulating durable control of HIV infection.
Федеральное государственное бюджетное учреждение «Научно-исследовательский институт комплексных проблем сердечно-сосудистых заболеваний» Сибирского отделения Российской академии медицинских наук, Кемерово, Россия
S. V. Ivanov,A. N. Sumin,Y. V. Kazachek,D. E. Philipiev,S. M. Gusev,E. S. Malyshenko,L. S. Barbarash +6 more
TL;DR: The outcomes of CAD surgical treatment were improved in this group of patients due to the implementation of a mul-assisted revascularization of coronary and non-coronary arteries.
Journal ArticleDOI
Transcriptional analysis of HIV-specific CD8 + T cells shows that PD-1 inhibits T cell function by upregulating BATF
Michael Quigley,Florencia Pereyra,Björn Nilsson,Filippos Porichis,Catia Fonseca,Quentin Eichbaum,Boris Julg,Jonathan L. Jesneck,Jonathan L. Jesneck,Kathleen Brosnahan,Sabrina Imam,Kate Russell,Ildiko Toth,Alicja Piechocka-Trocha,Douglas V. Dolfi,Jill M. Angelosanto,Alison Crawford,Haina Shin,Douglas S. Kwon,Jennifer Zupkosky,Loise M. Francisco,Gordon J. Freeman,E. John Wherry,Daniel Kaufmann,Daniel Kaufmann,Bruce D. Walker,Benjamin L. Ebert,Benjamin L. Ebert,Benjamin L. Ebert,W. Nicholas Haining +29 more
TL;DR: It is shown that PD-1 coordinately upregulates a program of genes in exhausted CD8+ T cells from humans and mice that includes upregulation of basic leucine transcription factor, ATF-like (BATF), a transcription factor in the AP-1 family that inhibit T cell function.
Journal ArticleDOI
Role of viral replication, antiretroviral therapy, and immunodeficiency in HIV-associated atherosclerosis.
Priscilla Y. Hsue,Peter W. Hunt,Amanda Schnell,S. Craig Kalapus,Rebecca Hoh,Peter Ganz,Jeffrey N. Martin,Steven G. Deeks +7 more
TL;DR: Chronic inflammation – which is higher in controllers than in HIV-uninfected persons – may account for early atherosclerosis in these patients, which can occur in the absence of antiretroviral therapy, detectable viremia, or overt immunodeficiency.
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