Valganciclovir Reduces T Cell Activation in HIV-Infected Individuals With Incomplete CD4+ T Cell Recovery on Antiretroviral Therapy
Peter W. Hunt,Jeffrey N. Martin,Elizabeth Sinclair,Lorrie Epling,Juli Teague,Mark A. Jacobson,Russell P. Tracy,Lawrence Corey,Steven G. Deeks +8 more
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TLDR
CMV (and/or other herpesvirus) replication is a significant cause of immune activation in HIV-infected individuals with incomplete antiretroviral therapy-mediated CD4(+) T cell recovery, and trends were significant even among those with undetectable plasma HIV RNA levels.Abstract:
Background. Elevated immune activation persists during treated human immunodeficiency virus (HIV) infection and is associated with blunted CD4 recovery and premature mortality, but its causes remain incompletely characterized. We hypothesized that asymptomatic cytomegalovirus (CMV) replication might contribute to immune activation in this setting. Methods. Thirty antiretroviral therapy‐treated HIV-infected CMV-seropositive participants with CD4 counts ,350 cells/mm 3 were randomized to receive valganciclovir 900 mg daily or placebo for 8 weeks, followed by an additional 4-week observation period. The primary outcome was the week 8 change in percentage of activated (CD38 1 HLA-DR 1 ) CD8 1 T cells. Results. Fourteen participants were randomized to valganciclovir and 16 to placebo. Most participants (21 [70%] of 30) had plasma HIV RNA levels ,75 copies/mL. The median CD4 count was 190 (IQR: 134‐232) cells/ mm 3 , and 12 (40%) of 30 had detectable CMV DNA in saliva, plasma, or semen at baseline. CMV DNA continued to be detectable at weeks 4‐12 in 7 (44%) of 16 placebo-treated participants, but in none of the valganciclovir-treated participants (P 5 .007). Valganciclovir-treated participants had significantly greater reductions in CD8 activation at weeks 8 (P 5 .03) and 12 (P 5 .02) than did placebo-treated participants. These trends were significant even among those with undetectable plasma HIV RNA levels. Conclusions. CMV (and/or other herpesvirus) replication is a significant cause of immune activation in HIVinfected individuals with incomplete antiretroviral therapy‐mediated CD4 1 T cell recovery.read more
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References
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Journal ArticleDOI
Microbial translocation is a cause of systemic immune activation in chronic HIV infection
Jason M. Brenchley,David Price,Timothy W. Schacker,Tedi E. Asher,Guido Silvestri,Srinivas S. Rao,Zachary Kazzaz,Ethan Bornstein,Olivier Lambotte,Daniel M. Altmann,Bruce R. Blazar,Benigno Rodriguez,Leia Teixeira-Johnson,Alan L. Landay,Jeffrey N. Martin,Frederick Hecht,Louis J. Picker,Michael M. Lederman,Steven G. Deeks,Daniel C. Douek +19 more
TL;DR: It is shown that increased lipopolysaccharide is bioactive in vivo and correlates with measures of innate and adaptive immune activation, which establish a mechanism for chronic immune activation in the context of a compromised gastrointestinal mucosal surface and provide new directions for therapeutic interventions that modify the consequences of acute HIV infection.
Journal ArticleDOI
Microbial translocation is a cause of systemic immune activation in chronic HIV infection
TL;DR: It is shown that circulating microbial products, probably derived from the gastrointestinal tract, are a cause of HIV-related systemic immune activation and increased lipopolysaccharide is bioactive in vivo and correlates with measures of innate and adaptive immune activation.
Journal ArticleDOI
Inflammatory and coagulation biomarkers and mortality in patients with HIV infection.
Lewis H. Kuller,Russell P. Tracy,Waldo H. Belloso,Stéphane De Wit,Fraser Drummond,H. Clifford Lane,Bruno Ledergerber,Jens D Lundgren,Jacqueline Neuhaus,Daniel E. Nixon,Nicholas I. Paton,James D. Neaton +11 more
TL;DR: IL-6 and D-dimer were strongly associated with an increased risk of all-cause mortality and Therapies that reduce the inflammatory response to HIV and decrease IL- 6 and D -dimer levels may warrant investigation.
Journal ArticleDOI
Life expectancy of individuals on combination antiretroviral therapy in high-income countries: a collaborative analysis of 14 cohort studies
Robert S. Hogg,Viviane D. Lima,Jonathan A C Sterne,Sophie Grabar,Manuel Battegay,M. Bonarek,A d'Arminio Monforte,Anna Esteve,Michael Gill,RJ Harris,Amy C. Justice,A. Hayden,F Lampe,Amanda Mocroft,Jan-Christian Wasmuth,Michael J. Mugavero,S Staszewski,A.I. van Sighem,Mari M. Kitahata,Jodie L. Guest,M Egger,Margaret T May +21 more
TL;DR: Life expectancy in HIV-infected patients treated with combination antiretroviral therapy increased between 1996 and 2005, although there is considerable variability between subgroups of patients.
Journal ArticleDOI
Broadly targeted human cytomegalovirus-specific CD4+ and CD8+ T cells dominate the memory compartments of exposed subjects
Andrew W. Sylwester,Bridget L. Mitchell,John B. Edgar,Cara Taormina,Christian Pelte,Franziska Ruchti,Paul R. Sleath,Kenneth H. Grabstein,Nancy Ann Hosken,Florian Kern,Jay A. Nelson,Louis J. Picker +11 more
TL;DR: The first glimpse of the total human T cell response to a complex infectious agent is provided and insight into the rules governing immunodominance and cross-reactivity in complex viral infections of humans is provided.
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