title: Valganciclovir reduces T cell activation in HIV-infected individuals with incomplete CD4+ T cell recovery on antiretroviral therapy.
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(+) HLA-DR(+)) CD8(+) 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 = .007). Valganciclovir-treated participants had significantly greater reductions in CD8 activation at weeks 8 (P = .03) and 12 (P = .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 HIV-infected individuals with incomplete antiretroviral therapy-mediated CD4(+) T cell recovery.
  
  
  BACKGROUND
  NCT00264290.
authors.affiliation: Department of Medicine, University of California, San Francisco, USA. phunt@php.ucsf.edu
authors.forename: Peter W
authors.initials: PW
authors.lastname: Hunt
authors.forename: Jeffrey N
authors.initials: JN
authors.lastname: Martin
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Sinclair
authors.forename: Lorrie
authors.initials: L
authors.lastname: Epling
authors.forename: Juli
authors.initials: J
authors.lastname: Teague
authors.forename: Mark A
authors.initials: MA
authors.lastname: Jacobson
authors.forename: Russell P
authors.initials: RP
authors.lastname: Tracy
authors.forename: Lawrence
authors.initials: L
authors.lastname: Corey
authors.forename: Steven G
authors.initials: SG
authors.lastname: Deeks
mesh_terms: D019380:Anti-HIV Agents / Q000494:pharmacology / Q000627:therapeutic use*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000502:physiology*; D003587:Cytomegalovirus / Q000502:physiology; D003586:Cytomegalovirus Infections / Q000150:complications / Q000276:immunology; D004279:DNA, Viral / Q000032:analysis / Q000097:blood; D015774:Ganciclovir / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects*; D012463:Saliva / Q000821:virology; D012661:Semen / Q000821:virology; D000077562:Valganciclovir; D014779:Virus Replication
chemical_list: D019380:Anti-HIV Agents; D004279:DNA, Viral; D000077562:Valganciclovir; D015774:Ganciclovir