Michael L Freeman1, Joseph C Mudd1, Carey L Shive2, Souheil-Antoine Younes1, Soumya Panigrahi1, Scott F Sieg1, Sulggi A Lee3, Peter W Hunt3, Leonard H Calabrese4, Sara Gianella5, Benigno Rodriguez1, Michael M Lederman1. 1. Center for AIDS Research, Division of Infectious Diseases and HIV Medicine, Department of Medicine, Case Western Reserve University/University Hospitals Case Medical Center. 2. Center for AIDS Research, Division of Infectious Diseases and HIV Medicine, Department of Medicine, Case Western Reserve University/University Hospitals Case Medical Center, Veterans Administration Medical Center, Cleveland, Ohio. 3. Department of Medicine, University of California San Francisco. 4. Department of Rheumatic and Immunologic Diseases, Cleveland Clinic Foundation, Ohio. 5. Division of Infectious Diseases, University of California San Diego, La Jolla.
Abstract
BACKGROUND: Persistent CD8 T-cell expansion, low CD4/CD8 T-cell ratios, and heightened inflammation persist in antiretroviral therapy (ART)-treated human immunodeficiency virus (HIV) infection and are associated with increased risk of morbid outcomes. We explored the role of cytomegalovirus (CMV) infection in CD8 lymphocytosis and inflammation in ART-treated HIV infection. METHODS: Absolute CD4 and CD8 T-cell counts were abstracted from clinical records and compared among 32 HIV-infected CMV-seronegative subjects, 126 age, CD4 and gender-matched HIV-infected CMV-seropositive subjects, and among 21 HIV-uninfected controls (9 CMV-negative, 12 CMV-positive). Plasma inflammatory indices were measured in a subset by ELISA. RESULTS: Median CD8 counts/µL were higher in HIV-positive/CMV-positive patients (795) than in HIV-positive/CMV-negative subjects (522, P = .006) or in healthy controls (451, P = .0007), whereas CD8 T-cell counts were similar to controls' levels in HIV-positive/CMV-negative subjects. Higher plasma levels of IP-10 (P = .0011), TNF-RII (P = .0002), and D-dimer (P = .0444) were also found in coinfected patients than in HIV-positive/CMV-negative subjects. CONCLUSIONS: CMV infection is associated with higher CD8 T-cell counts, resultant lower CD4/CD8 ratios, and increased systemic inflammation in ART-treated HIV infection. CMV infection may contribute to risk for morbid outcomes in treated HIV infection.
BACKGROUND: Persistent CD8 T-cell expansion, low CD4/CD8 T-cell ratios, and heightened inflammation persist in antiretroviral therapy (ART)-treated human immunodeficiency virus (HIV) infection and are associated with increased risk of morbid outcomes. We explored the role of cytomegalovirus (CMV) infection in CD8 lymphocytosis and inflammation in ART-treated HIV infection. METHODS: Absolute CD4 and CD8 T-cell counts were abstracted from clinical records and compared among 32 HIV-infected CMV-seronegative subjects, 126 age, CD4 and gender-matched HIV-infected CMV-seropositive subjects, and among 21 HIV-uninfected controls (9 CMV-negative, 12 CMV-positive). Plasma inflammatory indices were measured in a subset by ELISA. RESULTS: Median CD8 counts/µL were higher in HIV-positive/CMV-positive patients (795) than in HIV-positive/CMV-negative subjects (522, P = .006) or in healthy controls (451, P = .0007), whereas CD8 T-cell counts were similar to controls' levels in HIV-positive/CMV-negative subjects. Higher plasma levels of IP-10 (P = .0011), TNF-RII (P = .0002), and D-dimer (P = .0444) were also found in coinfectedpatients than in HIV-positive/CMV-negative subjects. CONCLUSIONS:CMV infection is associated with higher CD8 T-cell counts, resultant lower CD4/CD8 ratios, and increased systemic inflammation in ART-treated HIV infection. CMV infection may contribute to risk for morbid outcomes in treated HIV infection.
Authors: Naeem Khan; Naseer Shariff; Mark Cobbold; Rachel Bruton; Jenni A Ainsworth; Alan J Sinclair; Laxman Nayak; Paul A H Moss Journal: J Immunol Date: 2002-08-15 Impact factor: 5.422
Authors: Qin Ouyang; Wolfgang M Wagner; Anders Wikby; Steffen Walter; Geraldine Aubert; Anthony I Dodi; Paul Travers; Graham Pawelec Journal: J Clin Immunol Date: 2003-07 Impact factor: 8.317
Authors: Qin Ouyang; Wolfgang M Wagner; Wei Zheng; Anders Wikby; Ed J Remarque; Graham Pawelec Journal: Exp Gerontol Date: 2004-04 Impact factor: 4.032
Authors: Priscilla Y Hsue; Joan C Lo; Arlana Franklin; Ann F Bolger; Jeffrey N Martin; Steven G Deeks; David D Waters Journal: Circulation Date: 2004-03-15 Impact factor: 29.690
Authors: M Humbert; P Roux-Lombard; J Cerrina; A Magnan; G Simonneau; P Dartevelle; P Galanaud; J M Dayer; D Emilie Journal: Am J Respir Crit Care Med Date: 1994-06 Impact factor: 21.405
Authors: Victor Appay; P Rod Dunbar; Margaret Callan; Paul Klenerman; Geraldine M A Gillespie; Laura Papagno; Graham S Ogg; Abigail King; Franziska Lechner; Celsa A Spina; Susan Little; Diane V Havlir; Douglas D Richman; Norbert Gruener; Gerd Pape; Anele Waters; Philippa Easterbrook; Mariolina Salio; Vincenzo Cerundolo; Andrew J McMichael; Sarah L Rowland-Jones Journal: Nat Med Date: 2002-04 Impact factor: 53.440
Authors: Stephen R Morris; Bonnie Chen; Joseph C Mudd; Soumya Panigrahi; Carey L Shive; Scott F Sieg; Cheryl M Cameron; David A Zidar; Nicholas T Funderburg; Souheil-Antoine Younes; Benigno Rodriguez; Sara Gianella; Michael M Lederman; Michael L Freeman Journal: JCI Insight Date: 2020-06-04
Authors: Davey M Smith; Masato Nakazawa; Michael L Freeman; Christy M Anderson; Michelli F Oliveira; Susan J Little; Sara Gianella Journal: Clin Infect Dis Date: 2016-09-06 Impact factor: 9.079
Authors: Souheil-Antoine Younes; Michael L Freeman; Joseph C Mudd; Carey L Shive; Arnold Reynaldi; Soumya Panigrahi; Jacob D Estes; Claire Deleage; Carissa Lucero; Jodi Anderson; Timothy W Schacker; Miles P Davenport; Joseph M McCune; Peter W Hunt; Sulggi A Lee; Sergio Serrano-Villar; Robert L Debernardo; Jeffrey M Jacobson; David H Canaday; Rafick-Pierre Sekaly; Benigno Rodriguez; Scott F Sieg; Michael M Lederman Journal: J Clin Invest Date: 2016-06-20 Impact factor: 14.808
Authors: Stephanie Shiau; Alexis A Bender; Jane A O'Halloran; Erin Sundermann; Juhi Aggarwal; Keri N Althoff; Jason V Baker; Steven Deeks; Linda P Fried; Stephen Karpiak; Maile Y Karris; Thomas D Marcotte; Jean B Nachega; Joseph B Margolick; Kristine M Erlandson; David J Moore Journal: AIDS Res Hum Retroviruses Date: 2020-09-23 Impact factor: 2.205
Authors: Arcadio Agudelo-Hernandez; Yue Chen; Arlene Bullotta; William G Buchanan; Cynthia R Klamar-Blain; Luann Borowski; Sharon A Riddler; Charles R Rinaldo; Bernard J C Macatangay Journal: AIDS Date: 2017-09-24 Impact factor: 4.177