title: Quantitative effects of valacyclovir on the replication of cytomegalovirus (CMV) in persons with advanced human immunodeficiency virus disease: baseline CMV load dictates time to disease and survival. The AIDS Clinical Trials Group 204/Glaxo Wellcome 123-014 International CMV Prophylaxis Study Group.
abstract: Virus load is a major risk factor for disease in many human viral infections, especially human immunodeficiency virus (HIV) disease. The effect of cytomegalovirus (CMV) load on disease progression and the influence of antiviral chemotherapy on surrogate markers of replication was investigated in 310 patients with advanced HIV disease in a randomized controlled trial that compared the effects of valacyclovir with those of acyclovir. Sequential blood and urine samples were analyzed by polymerase chain reaction (PCR), for human CMV (HCMV) DNA. In multivariate analyses, elevated virus load in both blood and urine at baseline was associated with increased risk of HCMV disease (relative hazard, 1.49 and 1.44 per log increase, respectively). Elevated virus load in blood at baseline was also associated with a significantly shorter survival time (log rank, P=. 0001). In time-updated analyses, valacyclovir significantly suppressed the virus load in subjects who were PCR positive at baseline (in blood or urine), when compared with the combined acyclovir arms.
authors.affiliation: Department of Virology and HIV Research Unit, Royal Free and University College School of Medicine, London, NW3 2QG UK. vincent@rfhsm.ac.uk
authors.forename: V C
authors.initials: VC
authors.lastname: Emery
authors.forename: C
authors.initials: C
authors.lastname: Sabin
authors.forename: J E
authors.initials: JE
authors.lastname: Feinberg
authors.forename: M
authors.initials: M
authors.lastname: Grywacz
authors.forename: S
authors.initials: S
authors.lastname: Knight
authors.forename: P D
authors.initials: PD
authors.lastname: Griffiths
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000188:drug therapy* / Q000821:virology; D000212:Acyclovir / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000704:Analysis of Variance; D000998:Antiviral Agents / Q000627:therapeutic use*; D003587:Cytomegalovirus / Q000187:drug effects / Q000302:isolation & purification / Q000502:physiology*; D003586:Cytomegalovirus Infections / Q000188:drug therapy*; D018572:Disease-Free Survival; D015658:HIV Infections / Q000503:physiopathology*; D006801:Humans; D015999:Multivariate Analysis; D016133:Polymerase Chain Reaction; D011355:Prodrugs / Q000627:therapeutic use*; D012307:Risk Factors; D015996:Survival Rate; D013997:Time Factors; D000077483:Valacyclovir; D014633:Valine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D000998:Antiviral Agents; D011355:Prodrugs; D014633:Valine; D000077483:Valacyclovir; D000212:Acyclovir