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.
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.
Feinberg
J E
JE
Department of Medicine, University of Cincinnati, Ohio 45267-0405, USA. feinbej@email.uc.edu
Hurwitz
S
S
Cooper
D
D
Sattler
F R
FR
MacGregor
R R
RR
Powderly
W
W
Holland
G N
GN
Griffiths
P D
PD
Pollard
R B
RB
Youle
M
M
Gill
M J
MJ
Holland
F J
FJ
Power
M E
ME
Owens
S
S
Coakley
D
D
Fry
J
J
Jacobson
M A
MA
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
D000998:Antiviral Agents; D014633:Valine; D000077483:Valacyclovir; D000212:Acyclovir