TABLE 5.

Summary of randomized antiviral drug prophylaxis trials in solid-organ transplant recipients^d

Drug and type of transplant	Reference	Type of study	Number of patients studied (# of D+/R− patients)a	Prophylactic regimenb	Outcome(s)	CMV diseasec	Mortalityc
Acyclovir
Kidney	26	Primary and secondary prophylaxis, prospective, double-blind, placebo controlled	53 (6)	Acyclovir 800 mg p.o. 4 times a day for 12 wk beginning before transplant	Decreased CMV infection and disease, especially in the D+/R− subgroup	8% vs. 29%	4% vs. 6%
				vs.
			51 (7)	placebo
	236	Primary prophylaxis, prospective	22 (22)	Acyclovir 800–3,200 mg/day p.o. for 12 wk	No difference	40% vs. 40%	Not reported
				vs.
			10 (10)	no prophylaxis
	136	Primary and secondary prophylaxis (excluding D−/R−)	39 (13)	Acyclovir 800 mg p.o. 4 times a day for 12 wk plus CMV immunoglobulin every 2 wk for 16 wk	Decreased CMV infection with oral acyclovir only for donor-negative group; decreased CMV infection with oral ganciclovir in all	38% vs. 2.5%	5% vs. 2.5%
				vs.
			40 (14)	ganciclovir 1 g p.o. 3 times a day for 12 wk plus CMV immune globulin every 2 wk for 16 wk
Kidney, kidney-pancreas, kidney-islet cell, pancreas, liver	105	Primary and secondary prophylaxis, prospective, non-placebo controlled	133 (32)	Acyclovir 800 mg p.o. or 400 mg i.v. 4 times a day for 12 wk or for 6 wk after any antirejection therapy	Decreased CMV disease in the acyclovir group	21% vs. 32%	10% vs. 14%
				vs.
			133 (31)	ganciclovir 5 mg/kg i.v. twice a day for 7 days plus immunoglobulin (Sandoglobulin; Novartis Pharmaceuticals Corp., East Hanover, N.J.) or Minnesota CMV immunoglobulin 100 mg/kg on i.v. days 1, 4, and 7
Liver	396	Secondary prophylaxis, controlled, prospective	60 (0)	Acyclovir 500 mg/m2 i.v. 3 times a day for 10 days, then acyclovir 3,200 mg/day p.o. through 3 mo	Decreased CMV infection and disease	7% vs. 23%	“No effect on survival”
				vs.
			60 (0)	no prophylaxis
	423	Primary prophylaxis and preemptive therapy, controlled, prospective	24 (2)	Acyclovir 800 mg p.o. 4 times a day for 24 wk	Oral acyclovir ineffective	29% vs. 4%	13% vs. 13%
				vs.
			23 (2)	ganciclovir 5 mg/kg i.v. for 7 days when CMV culture positive
	145	Secondary prophylaxis (R+), prospective	37 (0)	Acyclovir 400 mg p.o. 5 times a day for 16 wk	Decreased CMV disease	5% vs. 27%	19% vs. 22%
				vs.
			36 (0)	no prophylaxis
emsHeart, lung, and kidney	21	Primary prophylaxis, prospective, stratified (type of transplant and prophylactic immunosuppression)	11 (11)	Acyclovir 800 mg p.o. 4 times a day for 12 wk	Acyclovir with or without immunoglobulin did not prevent primary CMV infection or disease	64% vs. 80%	9% vs. 0%
				vs.
			10 (10)	acyclovir 800 mg p.o. 4 times a day for 12 wk with immune globulin 300 mg/kg i.v. every 2 wk for 6 doses
Ganciclovir
Kidney (cadaver)	382	Primary prophylaxis	17 (17)	Ganciclovir 5 mg/kg i.v. twice a day for 14 days (days 14–28)	Delayed onset of CMV infection; reduced severity of CMV disease; no change in incidence of CMV infection or disease	47% vs. 73%	0% vs. 0%
				vs.
			17 (17)	No ganciclovir
	8	Primary prophylaxis, prospective, open-label, controlled	21 (4)	Ganciclovir 750 mg p.o. twice a day for 12 wk	Decreased CMV infection	5% vs. 27%	0% vs. 5%
				vs.
			22 (4)	no ganciclovir
Heart	273	Primary and secondary prophylaxis, stratified (R+ vs. D+/R−), prospective, double-blind	28 (9)	Ganciclovir 5 mg/kg i.v. 3 times a wk for 6 wk; then for another 2 wk for each treated rejection episode through 12 wk	Reduced CMV disease in D+/R− patients, reduced CMV disease morbidity in the R+ subgroup	11% vs. 71%	None
				vs.
			28 (7)	placebo
	299	Primary and secondary prophylaxis, stratified (R+ vs. D+/R−), prospective, double-blind, placebo controlled	76 (19)	Ganciclovir 5 mg/kg i.v. twice a day for 14 days, then 6 mg/kg 5 times a wk for 14 days	Reduced incidence of CMV illness in the R+ subgroup, delayed incidence of CMV shedding	16% vs. 43%	4% vs. 1%
				vs.
			73 (16)	placebo
	5	Secondary prophylaxis, prospective, non-placebo controlled	16 (0)	Ganciclovir 5 mg/kg i.v. twice a day for 14 days	Higher incidence of CMV disease in the immunoglobulin group	6% vs. 40%	6% vs. 13%
				vs.
			15 (0)	CMV immunoglobulin (Cytogam; Medimmune, Inc., Gaithersburg, Md.) 100 mg/kg within 24 h of transplant and at wk 2, 4, 6, 8, 10
Lung	104	Primary and secondary prophylaxis (excluding D−/R−)	13 (3)	Ganciclovir 5 mg/kg i.v. 4 times a day for 2 wk, starting day 7, then 5 mg/kg/day for 1 wk, then 5 mg/kg/day 5 days a wk till day 90	Decreased CMV infection and disease, increased median infection-free duration	0% vs. 25%	15% vs. 25%
				vs.
			12 (3)	ganciclovir 5 mg/kg i.v. 4 times a day for 2 weeks, starting day 7, then 5 mg/kg/day for 1 wk, then acyclovir 800 mg p.o. 4 times a day til day 90
Lung, heart-lung	195	Primary and secondary prophylaxis	35 (5)	Ganciclovir 5 mg/kg i.v. twice a day on days 8–21, then 5 mg/kg i.v. till day 90	no difference in CMV infection nor disease	51% vs. 30%	14% vs. 35%
				vs.
			37 (5)	ganciclovir 5 mg/kg i.v. twice a day on days 8–21, then 5 mg/kg/day i.v. 3 times a wk till day 90
Liver	232	Primary prophylaxis, prospective, placebo controlled	29	Ganciclovir 5 mg/kg/day for 30 days with i.v. immunoglobulin 1 g/kg once, then 500 mg/kg/wk at wk 1–8, then 2×/week at wk 10–16	No difference in CMV disease	17% vs. 26%	21% vs. 15%
				vs.
			27	placebo plus immunoglobulin
	172	Primary and secondary prophylaxis, pediatric	24 (7)	Ganciclovir 5 mg/kg i.v. twice a day for 2 wk, then acyclovir 800 mg/m2 p.o. 4 times a day for 50 wk	No difference	29% vs. 84%
				vs.
			24 (5)	ganciclovir 5 mg/kg i.v. twice a day for 2 wk
	143	Primary prophylaxis, prospective, double-blind, placebo controlled	150 (21)	Ganciclovir 1,000 mg p.o. 3 times a day for 98 days	Effective in decreasing CMV disease	5% vs. 19%	7% vs. 10%
				vs.
			154 (25)	placebo
	18	Primary and secondary prophylaxis, prospective, non-placebo controlled	83 (12)	Ganciclovir 5mg/kg i.v. twice a day for 14 days, then acyclovir 800 mg p.o. 4 times a day for 106 days	Decreased CMV disease in ganciclovir group, even for patients in the D+/R− group	11% vs. 23%	7% vs. 8%
				vs.
			84 (13)	acyclovir 800 mg p.o. 4 times a day for 120 days
	319	Primary and secondary prophylaxis, prospective	52 (9)	Acyclovir 5 mg/kg/day i.v. till discharge, then 5 mg/kg/day p.o. with immunoglobulin (Sandoglobulin; Novartis Pharmaceuticals Corp., East Hanover, N.J.) 200 mg/kg i.v. twice a wk	Decreased CMV disease in ganciclovir group	15% vs. 4%	14% vs. 13%
				vs.
			52 (7)	ganciclovir 5 mg/kg/day i.v. till discharge, then acyclovir 5 mg/kg/day p.o. with immunoglobulin 200 mg/kg i.v. twice a wk
	284	Primary and secondary prophylaxis, prospective	71 (11)	Acyclovir 800 mg p.o. 4 times a day for 3 mo	Decreased CMV infection and disease; delayed onset of CMV infection in ganciclovir group; no decrease in primary CMV infection	28% vs. 9%	7% vs. 12%
				vs.
			68 (7)	ganciclovir 5 mg/kg/day i.v. for 2 wk, then acyclovir 800 mg p.o. 4 times a day for 2.5 mo
	72	Primary and secondary prophylaxis (excluding D−/R−), prospective	33 (3)	Ganciclovir 5 mg/kg i.v. twice a day for 14 days during wk 3 and 4 posttransplantation	No difference in clinical infection; lower incidence of serologically diagnosed infection in ganciclovir group	27% vs. 34%	3% vs. 19%
				vs.
			32 (7)	no prophylaxis
	497	Primary and secondary prophylaxis, prospective, non-placebo controlled	124 (10)	Ganciclovir 6 mg/kg/day i.v. on days 1–30; then Monday–Friday through day 100	Decreased CMV infection and disease in ganciclovir group	0.8% vs. 10%	15% vs. 14%
				vs.
			126 (11)	acyclovir 10 mg/kg i.v. 3 times a day till discharge; then 800 mg p.o. 4 times a day till day 100

^aIf known, the number of CMV-negative patients given donor-positive organs (D⁺/R⁻) is shown in parentheses. 

^bp.o., peroral; i.v., intravenous. 

^cAmong patients given the drug, the percentage refers to the first versus the second listed regimen. 

^dModified from references 334a and 336a with permission of the publisher.