title: A randomized, double-blind trial of valaciclovir prophylaxis for cytomegalovirus disease in patients with advanced human immunodeficiency virus infection. AIDS Clinical Trials Group Protocol 204/Glaxo Wellcome 123-014 International CMV Prophylaxis Study Group.
abstract: Cytomegalovirus (CMV) disease is a common complication of advanced human immunodeficiency virus (HIV) infection. Administration of oral valaciclovir, a valine ester of acyclovir, achieves sufficient plasma acyclovir levels to inhibit many clinical isolates. Acyclovir has been associated with enhanced survival in AIDS but not with CMV disease prevention. CMV-seropositive patients (1227) with CD4 cell counts <100/mm3 were enrolled in a randomized, double-blind trial. Valaciclovir, 8 g/day, was compared with acyclovir, 3.2 or 0.8 g/day, for CMV prevention; all three arms were compared for survival. The confirmed CMV disease rate was 11.7% among valaciclovir recipients and 17.5% in the pooled acyclovir arms, a 33% reduction in risk. Time to confirmed CMV disease was significantly longer for the valaciclovir group (P = .03). A trend toward earlier mortality for valaciclovir recipients was seen (P = .06). Toxicity and earlier medication discontinuation were more common in this group. Valaciclovir significantly reduces the risk of CMV disease. Further exploration of a better-tolerated dose is warranted.
authors.affiliation: Department of Medicine, University of Cincinnati, Ohio 45267-0405, USA. feinbej@email.uc.edu
authors.forename: J E
authors.initials: JE
authors.lastname: Feinberg
authors.forename: S
authors.initials: S
authors.lastname: Hurwitz
authors.forename: D
authors.initials: D
authors.lastname: Cooper
authors.forename: F R
authors.initials: FR
authors.lastname: Sattler
authors.forename: R R
authors.initials: RR
authors.lastname: MacGregor
authors.forename: W
authors.initials: W
authors.lastname: Powderly
authors.forename: G N
authors.initials: GN
authors.lastname: Holland
authors.forename: P D
authors.initials: PD
authors.lastname: Griffiths
authors.forename: R B
authors.initials: RB
authors.lastname: Pollard
authors.forename: M
authors.initials: M
authors.lastname: Youle
authors.forename: M J
authors.initials: MJ
authors.lastname: Gill
authors.forename: F J
authors.initials: FJ
authors.lastname: Holland
authors.forename: M E
authors.initials: ME
authors.lastname: Power
authors.forename: S
authors.initials: S
authors.lastname: Owens
authors.forename: D
authors.initials: D
authors.lastname: Coakley
authors.forename: J
authors.initials: J
authors.lastname: Fry
authors.forename: M A
authors.initials: MA
authors.lastname: Jacobson
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000188:drug therapy* / Q000517:prevention & control / Q000821:virology; D000212:Acyclovir / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D000284:Administration, Oral; D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D003586:Cytomegalovirus Infections / Q000175:diagnosis / Q000188:drug therapy* / Q000517:prevention & control; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D000077483:Valacyclovir; D014633:Valine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D000998:Antiviral Agents; D014633:Valine; D000077483:Valacyclovir; D000212:Acyclovir