[Comparison of the effectiveness of acyclovir and vidarabine in superficial herpes keratitis]. Acyclovir and vidarabine in the treatment of ulcerative herpes simplex keratitis. A double-blind, multicenter clinical trial of acyclovir vs idoxuridine for treatment of epithelial herpes simplex keratitis. A randomised double-blind clinical trial of acyclovir (Zovirax) and adenine arabinoside in herpes simplex corneal ulceration. Combination therapy for dendritic keratitis with acyclovir and vidarabine. [Acyclovir and trifluorothymidine in herpetic kerato-uveitis. A comparative clinical study. Indications for corticoid therapy]. Randomised double-blind trial of acyclovir and idoxuridine in dendritic corneal ulceration. Ganciclovir ophthalmic gel (Virgan; 0.15%) in the treatment of herpes simplex keratitis. Ganciclovir ophthalmic gel, 0.15%: a valuable tool for treating ocular herpes. Treatment of herpes simplex keratitis: comparison of acyclovir and vidarabine. [Superficial herpes simplex keratitis. Double-blind comparative trial of acyclovir and idoxuridine (author's transl)]. Combination therapy for dendritic keratitis with acyclovir and alpha-interferon. Acyclovir and idoxiuridine treatment of herpes simplex keratitis--a double blind clinical study. Oral acyclovir (Zovirax) in herpes simplex dendritic corneal ulceration. Comparative study of acyclovir and 5 I.D.U. in the management of viral corneal ulcer. A comparison of acyclovir and idoxuridine as treatment for ulcerative herpetic keratitis. A double-controlled evaluation of acyclovir and vidarabine for the treatment of herpes simplex epithelial keratitis. Efficacy of four antiviral agents in the treatment of uncomplicated herpetic keratitis. A comparison between acyclovir and trifluorothymidine ophthalmic ointment in the treatment of epithelial dendritic keratitis. A double blind, randomized parallel group trial. Combination therapy of recombinant human alpha 2 interferon and acyclovir in the treatment of herpes simplex keratitis. Trifluorothymidine versus adenine arabinoside in the treatment of herpes simplex keratitis. Acyclovir and debridement in the treatment of ulcerative herpetic keratitis. Vidarabine therapy of simple and IDU-complicated herpetic keratitis. Combination therapy for dendritic keratitis with human leukocyte interferon and acyclovir. Acyclovir in the treatment of herpetic keratitis. Randomized controlled trial of oral ganciclovir versus oral acyclovir after induction with intravenous ganciclovir for long-term prophylaxis of cytomegalovirus disease in cytomegalovirus-seropositive liver transplant recipients. Randomised double-blind trial of acyclovir (Zovirax) and adenine arabinoside in herpes simplex amoeboid corneal ulceration. Double--blind clinical trial of adenine arabinoside and idoxuridine in herpetic corneal ulcers. A randomized prospective controlled trial of oral acyclovir versus oral ganciclovir for cytomegalovirus prophylaxis in high-risk kidney transplant recipients. High-dose acyclovir compared with short-course preemptive ganciclovir therapy to prevent cytomegalovirus disease in liver transplant recipients. A randomized trial. Oral acyclovir in the management of dendritic herpetic corneal ulceration. Prevention of primary cytomegalovirus disease in organ transplant recipients with oral ganciclovir or oral acyclovir prophylaxis. A prospective randomized trial comparing sequential ganciclovir-high dose acyclovir to high dose acyclovir for prevention of cytomegalovirus disease in adult liver transplant recipients. A comparative randomised study of valacyclovir vs. oral ganciclovir for cytomegalovirus prophylaxis in renal transplant recipients. Comparison of intravenous ganciclovir followed by oral acyclovir with intravenous ganciclovir alone for prevention of cytomegalovirus and Epstein-Barr virus disease after liver transplantation in children. A prospective randomized study of acyclovir versus ganciclovir plus human immune globulin prophylaxis of cytomegalovirus infection after solid organ transplantation. A comparison of ganciclovir and acyclovir to prevent cytomegalovirus after lung transplantation. Failure of high-dose oral acyclovir with or without immune globulin to prevent primary cytomegalovirus disease in recipients of solid organ transplants. Oral acyclovir prophylactic treatment of herpes simplex infection after bone marrow transplantation. A controlled trial comparing vidarabine with acyclovir in neonatal herpes simplex virus infection. Infectious Diseases Collaborative Antiviral Study Group. Bromovinyldeoxyuridine and interferon treatment in ulcerative herpetic keratitis: a double masked study. Efficacy and safety of valganciclovir vs. oral ganciclovir for prevention of cytomegalovirus disease in solid organ transplant recipients. Multicenter collaborative trial of intravenous acyclovir for treatment of mucocutaneous herpes simplex virus infection in the immunocompromised host. Treatment of herpetic keratitis. Valacyclovir for cytomegalovirus prophylaxis reduces the risk of acute renal allograft rejection. A controlled trial of oral acyclovir for the prevention of stromal keratitis or iritis in patients with herpes simplex virus epithelial keratitis. The Epithelial Keratitis Trial. The Herpetic Eye Disease Study Group. Oral acyclovir in herpes zoster ophthalmicus. Epidermal growth factor in the topical treatment of herpetic corneal ulcers. Randomised comparison of ganciclovir and high-dose acyclovir for long-term cytomegalovirus prophylaxis in liver-transplant recipients. Efficacy of oral ganciclovir in prevention of cytomegalovirus infection in post-kidney transplant patients. Prophylaxis of cytomegalovirus infection in liver transplantation: a randomized trial comparing a combination of ganciclovir and acyclovir to acyclovir. NIDDK Liver Transplantation Database. Oral acyclovir therapy for mucocutaneous herpes simplex virus infections in immunocompromised marrow transplant recipients. Three- or four- versus two-drug antiretroviral maintenance regimens for HIV infection. Randomised trial of efficacy and safety of oral ganciclovir in the prevention of cytomegalovirus disease in liver-transplant recipients. The Oral Ganciclovir International Transplantation Study Group [corrected]. Combination therapy for dendritic keratitis. High-titer alpha-interferon and trifluridine. A prospective, 96-week study of the impact of Trizivir, Combivir/nelfinavir, and lamivudine/stavudine/nelfinavir on lipids, metabolic parameters and efficacy in antiretroviral-naive patients: effect of sex and ethnicity. Once-daily intravenous acyclovir for prophylaxis of herpes simplex virus reactivation after marrow transplantation. Valacyclovir versus acyclovir for HSV prophylaxisin neutropenic patients. Double controlled comparison of IDU and trifluorothymidine in thirty-three patients with superficial herpetic keratitis. Oral acyclovir for prevention of herpes simplex virus reactivation after marrow transplantation. Clinical evaluation of adenine arabinoside and trifluorothymidine in the treatment of corneal ulcers caused by herpes simplex virus. Antioxidant therapy for chronic hepatitis C after failure of interferon: results of phase II randomized, double-blind placebo controlled clinical trial. Viral prophylaxis in combined pancreas-kidney transplant recipients. Oral acyclovir prophylaxis against herpes simplex virus in non-Hodgkin lymphoma and acute lymphoblastic leukaemia patients receiving remission induction chemotherapy. A randomised double blind, placebo controlled trial. Acyclovir given as prophylaxis against oral ulcers in acute myeloid leukaemia: randomised, double blind, placebo controlled trial. Controlled trial of prophylactic versus therapeutic use of ganciclovir after liver transplantation in adults. [Double-blind treatment of ocular herpes simplex: Vira-A and acyclovir]. Prophylactic oral ganciclovir compared with deferred therapy for control of cytomegalovirus in renal transplant recipients.
In a double-blind clinical trial 28 patients with primary and recurrent herpetic corneal ulcerations were treated either with 3% Acyclovir eye ointment or 3% Adenosine Arabinoside eye ointment. In 11 out of 14 (78%) patients treated with Acyclovir and 8 out of 14 (57%) patients treated with Adenosine Arabinoside the ulcerations healed within a treatment period of 6.5 days and 8 days respectively (no statistical significance). However, the results revealed that Acyclovir was more effective. Both drugs were well tolerated. In a masked controlled study, we treated 41 patients who had active herpes simplex corneal ulcers with either 3% acyclovir of 3% vidarabine ointment five times daily for 14 days. There was no statistically significant difference between the two drugs with reference to mean healing time, efficacy of healing, development of stromal keratitis or iritis, post-treatment visual acuity, or adverse reaction. Thirty patients randomized to the Acyclovir (ACV) group (26 with dendritic lesions, 4 geographic lesions) and 34 patients randomized to the idoxuridine (IDU) treatment group (26 dendritic lesions, 8 geographic lesions) with epithelial herpetic keratitis were evaluated for efficacy and adverse reactions in a multi-center, double-masked, randomized, stratified trial. Patients were treated with either 3% acyclovir ophthalmic ointment or 0.5% idoxuridine ophthalmic ointment five times a day for 14 days. The results of the trial indicated no significant difference between ACV and IDU as antiviral agents in the treatment of epithelial herpetic keratitis. The overall healing patterns of ACV and IDU adjusted for lesion type and prognostic factors, including presenting condition (initial or recurrent disease), duration of symptoms, prior ophthalmic steroid use, and positive pretreatment herpesvirus culture, as well as, the healing patterns within each lesion type adjusted for these factors, were not significantly different between the two treatment groups. There was no significant difference between the two groups in the frequency of development of deeper involvement. The only significant difference (P less than 0.01) in the frequency of development of adverse reactions was found in the incidence of development of superficial punctate epitheliopathy (IDU-42%, ACV-11%). A double-blind clinical trial of 3% acyclovir (Zovirax) and 3% adenosine arabinoside (ara-A, Vidarabine) in 93 patients with herpetic corneal ulceration is presented. Ulcers in 45 (94%) of acyclovir-treated patients and 37 (82%) ara-A-treated patients healed within 14 days. Patients treated with acyclovir healed more rapidly than those treated with ara-A (p less than 0.01). No serious adverse effects were observed. We treated 32 patients with dendritic keratitis with a combination of acyclovir 3% ointment and vidarabine 3% ointment or acyclovir and placebo. Patients with acyclovir alone healed in an average time of 7.7 days, while patients on the combination healed in an average of 6 days. Only one patient in the acyclovir and vidarabine group had a healing time longer than 7 days, whereas six patients in the acyclovir and placebo group had healing times longer than 7 days. By the median test, this difference in healing times was statistically significant (p = 0.035), and the combination prevented cases of prolonged ulceration. The relative efficacy of aciclovir (ACV) and trifluorothymidine (TFT) was evaluated in a randomized, open clinical trial of 37 patients with herpetic kerato-uveitis. Twenty-one patients were treated with ACV and 16 with TFT. Topical steroids were withheld as long as the degree of inflammation permitted. Although both drugs were effective in healing the herpetic corneal ulcers, TFT had a significantly shorter healing time than ACV. However, ACV was more effective in treating the iridocyclitis than TFT. In 5 cases the keratouveitis responded to ACV alone, while only one case was successfully managed with TFT alone. Both drugs seemed to prevent steroid-induced epithelial complications and no significant side-effects were observed with either drug. The treatment of herpetic keratouveitis with single agents such as ACV and TFT is dependent upon rapidly instituting therapy and minimizing the use of topical steroids. The apparently good intraocular penetration of ACV and TFT may decrease the need for adjunctive steroid therapy and thereby minimize the risks of facilitated viral replication and steroid-dependence. The results of a randomised double-blind clinical trial of 3% acyclovir and 0.5% idoxuridine (IDU) ophthalmic ointments in 60 patients with corneal dendritic ulceration are presented. Ulcers in all 30 patients treated with acyclovir healed compared with 22 (76%) of 29 patients treated with IDU (P < 0.01). Patients treated with acyclovir healed more rapidly (average 4.4 days) than those who received IDU (average 9.2 days) (P < 0.01). No serious side effects were observed, though transient stinging was recorded in 8 patients receiving acyclovir and in 2 patients receiving IDU. Other side effects in the IDU treated group were watering in 2 patients and superficial punctate erosions in 6 patients. Ganciclovir is a broad-spectrum virustatic agent. Its efficacy and safety after ocular application have been demonstrated in studies of herpetic keratitis in rabbits. Two strengths of ganciclovir gel (0.05 and 0.15%) were compared with 3% acyclovir ointment in the treatment of superficial herpes simplex keratitis in humans.
                Two multicenter randomized clinical trials were carried out in Africa (Trial 1) and Europe (Trial 2). Sixty-seven patients (Trial 1) and 37 patients (Trial 2) from herpetic ulceration were recruited.
                The results showed no statistically significant difference between the treatment groups, although the healing rates tended to be better in the group receiving 0.15% ganciclovir gel, with healing rates of 85% (Trial 1) and 83% (Trial 2) as compared with 72% (Trial 1) and 71% (Trial 2) in the group receiving acyclovir ointment. Local tolerance was found to be superior with the gel formulation of ganciclovir with fewer complaints of discomfort (stinging, burning) or blurred vision after application of the drug. Systemic absorption of the drug was low. No hematologic changes were detected.
                These findings support the efficacy of ganciclovir gel in the treatment of ulcerative herpes simplex keratitis and demonstrate its superior local tolerance when compared with acyclovir ointment. Ocular herpes simplex virus (HSV) infection remains a major cause of corneal blindness. Several topical and oral antiviral medications have been used to treat herpetic keratitis. Advances in topical ophthalmic antivirals have been made over the past several decades. The first antivirals that were discovered were cytotoxic, while the antivirals developed more recently, such as acyclovir and ganciclovir, have exceeded these drugs in both efficacy and tolerability. Commercially available outside of the US since 1996, ganciclovir ophthalmic gel, 0.15% (GCV 0.15%, European tradename: Virgan((R))) is sold in more than 30 countries and has become the standard of care in treating acute herpetic keratitis. GCV 0.15% has been studied in animal models of ocular herpes, in healthy volunteers, and in several clinical studies. It has been found to be safe and effective at treating acute superficial herpetic keratitis. Previous preclinical studies of ganciclovir have shown activity against several common adenovirus strains and one recent clinical study demonstrated clinical effect against adenoviral conjunctivitis. This review is intended to provide a comprehensive overview of the GCV 0.15%, including a brief summary of the etiology and available treatments for ocular HSV, an explanation of GCV 0.15% mechanism of action, a compendium of preclinical and clinical GCV 0.15% studies, and an introduction into new areas of interest involving this drug. At three university centres 66 patients presenting with herpetic dendritic or geographic ulcers participated in a double-blind comparative study of 3% acyclovir and 3% vidarabine ointment. There was healing in 31 (97%) of the 32 patients treated with acyclovir, in a mean time of 6.3 days, and in 30 (88%) of the 34 treated with vidarabine, in a mean time of 7.1 days. The two medications were statistically equally effective, no difference being demonstrated in the healing rate, in the frequency of punctate epithelial keratitis or stromal keratitis, or in the final visual acuity. In a double-blind, randomized trial 52 patients with superficial herpes simplex keratitis were treated with a new antiviral compound, acylclovir (ACV) 3% ointment, or with idoxuridine (IDU) 0.5% ointment. No statistically significant difference was found in the number of patients cured with either drug, but healing was achieved more rapidly with ACV than with IDU. Fifty-nine patients with superficial herpetic keratitis were treated with 3% acyclovir ointment five times a day in combination with alpha-interferon (30 million IU/mL) or albumin-placebo once a day in a stratified double-masked clinical trial. All patients had minimal wiping of the superficial lesion to isolate virus. The healing time of the corneal ulcers was substantially lower with the combination of acyclovir and interferon than with the combination of acyclovir and placebo. Only minor toxic effects were observed. The combination of acyclovir and interferon appears to be the best presently known treatment for dendritic keratitis. 38 patients with herpes simplex keratitis were treated in double blind clinical trial. 18 patients (10 with pure epithelial and 8 with accompanying stromal affection) were treated with 3% acyclovir (ACV) eye ointment, and 20 patients (10 with pure epithelial and 10 with accompanying stromal affection) were treated with 0.5% idoxiuridine (IDU). The cure rate was 94% in the ACV group compared to 70% in the IDU group. This was significantly higher in the ACV group. Only minor adverse reactions were recorded. Sixty patients with simple dendritic corneal ulceration were randomly assigned to double blind treatment with either acyclovir tablets (400 mg) or acyclovir ophthalmic ointment administered five times daily. There was no significant difference in the proportions of patients healed in either treatment group (88.9% on oral acyclovir and 96.6% on acyclovir ointment). The median healing time was five days in both groups. No systemic or significant local side effects were noted in either treatment group. Trough levels of acyclovir in the tear fluid of those who received the oral preparation were within or above the range of mean in-vitro ID50 levels for herpes simplex virus type 1. We conclude that oral administration of acyclovir (400 mg, five times daily) may be an effective alternative to topical therapy in selected patients. Thus, we found that the role of Acyclovir in the treatment of viral corneal ulcer is definitely better and quicker. It takes less time for healing of corneal ulcer and as a result less hospitalisation is needed. Sixty patients were treated with either acyclovir 2% ointment or idoxuridine 1% ointment 5 times a day in a stratified randomised double-blind clinical trial. The 2 antiviral agents were equally effective. nan To evaluate the efficacy of four antiviral agents--1% idoxuridine ointment (group 1), 2% trifluorothymidine ointment (group 2), 3% acyclovir ointment (group 3) and 1% bromovinyldeoxyuridine (BVDU) ointment (group 4)--in herpes simplex keratitis.
                Randomized double-blinded clinical trial.
                Tertiary care institution in New Delhi.
                Eighty patients with uncomplicated herpes simplex keratitis of recent onset who had not previously received antiviral treatment.
                Cure rate, frequency and severity of side effects.
                Cure rates of 60%, 90%, 90% and 95% were obtained in groups 1, 2, 3 and 4 respectively. The average healing time was 13.4, 8.9, 8.5 and 7.5 days respectively. Side effects (follicular conjunctivitis, epithelial keratopathy and stinging) were more frequent in group 1 than in the other groups.
                BVDU has a more pronounced therapeutic effect than idoxuridine, trifluorothymidine and acyclovir in uncomplicated epithelial herpetic disease of recent onset that has not previously been treated. This report presents the results of a double blind randomized study comprising 50 patients with epithelial herpes simplex keratitis. Twenty-five patients received 3% acyclovir ophthalmic ointment, the other 25 patients 2% trifluorothymidine (TFT) ophthalmic ointment. The mean duration of treatment in the 2 study groups before healing of the epithelial ulceration was obtained was 6.7 days and 5.9 days, respectively (no statistically significant difference). Two patient (8%) in the acyclovir group and 1 patient (4%) in the TFT group failed to heal within 14 days of treatment. No clinically significant adverse effects were recorded. No statistical difference was found in both partial and complete healing time in acute epithelial herpetic keratitis between the ACV-recombinant human alpha 2 IFN (both "eyedrops" and "eyerods") and Buffy coat human leucocyte alpha IFN. A highly significant difference was found in both partial and complete healing time between the ACV-IFN combination versus the ACV-Placebo combination. The combination of ACV and recombinant human alpha 2 arg IFN is a potent anti-herpetic treatment. Trifluorothymidine (TFT) and adenine arabinoside (ara-A) are effective antiviral drugs with a very low toxicity for the cornea. In our study no difference between these 2 drugs in antiviral activity was noted. The average healing time for TFT was 11-14 days and for ara-A 10-54 days. These data differ markedly from those of other studies. This was the result of the use of additional criteria for healing of the lesion. Not only absence of fluorescein staining of the cornea but also the absence of oedema and cystic changes in the epithelium over the previous ulcer were considered criteria for healing. In addition to clearly defined healing criteria and the healing time we found the interval between the first symptoms and the commencement of the therapy of greatest importance in the clinical evaluation of antiviral drug efficacy. An effort was made to approximate this relationship for TFT and ara-A mathematically. We treated 25 patients with dendritic keratitis with debridement and 3% acyclovir ointment and another 25 with acyclovir alone. The patients were randomly assigned to the two treatment groups. There were only minimal adverse effects in both groups. The combination of debridement and acyclovir produced a significantly more rapid healing rate than did acyclovir alone. Factors associated with prolonged healing time were duration of symptoms (longer than one week), length of the epithelial defect (greater than 4 mm), proximity of the defect to the corneoscleral limbus (less than 2 mm), and the presence of stromal inflammation. Large scale, multiclinic evaluations of vidarabine (Ara-A, Vira A, adenine arabinoside) for treating herpetic keratitis have been conducted as double-blind studies (169 patients) in comparison with IDU and open studies (146 patients). In the open studies, the disease in the majority of patients had been refractory to IDU. The effects of vidarabine and IDU were approximately the same in improvement of symptoms (lacrimination, photophobia, sensitivity) and percent of and time for corneal reepithelialization. With vidarabine, significantly more patients had improved distant visual acuity than did with IDU. In the open studies, vidarabine also was effective. Of 116 patients whose ulcers had not responded to IDU, 91 (78%) had reepithelialization within four weeks of treatment with vidarabine. On the basis of results from these studies, vidarabine appears to be a safe and effective drug for treating herpes simplex keratitis. We treated 45 patients with virologically verified dendritic keratitis with a combination of interferon and acyclovir 3% or with placebo and acyclovir 3% in a double-masked study. One drop of human leukocyte interferon (30 X 10(6) IU/ml) or albumin-placebo was administered daily. Acyclovir ointment was applied five times daily. The mean healing time of the corneal ulcers in 24 patients treated with interferon and acyclovir was 3.9 days and the mean healing time in 21 patients treated with placebo and acyclovir was seven days. The difference was significant (P less than .001). Fourty-three eyes with active dendritic keratitis, nearly one third of which had failed to respond to other antiviral agents, were treated with acyclovir with or without preceding debridement. The patients were randomly selected. No statistical difference could be demonstrated between the 2 groups in terms of rate of healing or in efficacy of cure. Acyclovir also seemed to be effective in stromal corneal lesions. There were only minor side effects. Without effective antiviral prophylaxis, cytomegalovirus (CMV) disease is a common cause of morbidity and mortality after liver transplantation. In this randomized, controlled trial, we compared the efficacy and safety of oral ganciclovir with oral acyclovir after induction with intravenous (IV) ganciclovir for long-term prophylaxis of CMV disease in CMV-seropositive liver transplant recipients.
                Patients were initially administered IV ganciclovir at a dose of 6 mg/kg per day from day 1 to day 14 after transplantation followed by either oral ganciclovir (1 g every 8 hr) or oral acyclovir (800 mg every 6 hr) from day 15 to day 100 after transplantation.
                CMV disease occurred in only 1 of 110 patients (0.9%) receiving ganciclovir compared with 8 of 109 patients (7.3%) receiving acyclovir within the first year after transplantation (P =0.019). There was one case of CMV colitis in the ganciclovir group, whereas four cases of CMV syndrome, three cases of CMV pneumonia, and one case of CMV hepatitis developed in the acyclovir group. The only death from CMV disease occurred in an acyclovir-treated patient with CMV pneumonia. Both oral ganciclovir and oral acyclovir were generally well tolerated. Reversible leukopenia (decline in white blood cell count to <3.0 x 10(9)/L) was more common with oral ganciclovir (38/110 patients, 35%) than with oral acyclovir (20/109 patients, 18%) (P =0.009). The emergence of ganciclovir-resistant strains of CMV was not found during the study.
                A prophylactic regimen of 2 weeks of IV ganciclovir followed by an additional 12 weeks of oral ganciclovir is superior to a similar regimen of IV ganciclovir followed by oral acyclovir and almost completely eliminates CMV disease after liver transplantation. This superior protection against CMV disease extends up to 1 year after transplantation and is not associated with ganciclovir resistance. Fifty-one patients were treated in a dual-centre, double-blind comparison of acyclovir and adenine arabinoside in herpetic amoeboid (geographic) corneal ulceration. Twenty-four of the 25 patients receiving acyclovir healed in a mean time of 12.2 days, while 24 of the 26 patients treated with adenine arabinoside healed in a mean time of 11.0 days. There was no statistically significant difference between the two groups in terms of healing. A second analysis, excluding any patients who had received antiviral treatment immediately prior to entry into the study, showed that 18 of the 19 who received acyclovir healed in an average of 11.7 days and 18 of the 19 recipients of adenine arabinoside healed in a mean time of 11.2 days. Again the difference was not statistically significant. The results are reported of a fully controlled randomized double-blind clincial trial of adenine arabinoside and idoxuridine ointment in sixty patients with herpetic ulceration of the cornea. Although both antivirals showed a trend towards superiority over placebo, the therapeutic effect did not reach statistical significance in spite of the known efficacy in laboratory animals. Further studies in rabbits are reported; these indicate that systemic immunity may play a role in combating virus proliferation in recurrent disease, and it is considered this disguises the efficacy of topical antiviral therapy in clinical trials, thus necessitating an estimated requirement for approximately fifty patients per treatment group to obtain significant effects. It is concluded that an antiviral is valuable in the treatment of ulcerative herpetic keratitis, particularly in primary disease and in the presence of systemic and local immunosuppression after the use of topical adrenocorticosteroid. In recurrent disease, where a trigger factor is known, experience has shown that therapy can be profitably administered before the onset of clinical disease. Posttransplantation cytomegalovirus (CMV) infection remains a significant cause of morbidity in kidney transplant recipients. We performed a randomized prospective controlled trial of oral acyclovir versus oral ganciclovir for CMV prophylaxis in a group of renal allograft recipients considered at high risk for CMV disease due to the use of OKT3 induction therapy.
                A total of 101 recipients of cadaveric (83) and zero haplotype-matched live donor (18) kidney transplants were entered into the trial. A total of 22 D-R- patients received no prophylaxis. Twenty-seven D+R-, 29 D+R+, and 23 D-R+ patients were randomized to receive 3 months of either oral acyclovir (800 mg q.i.d.) or oral ganciclovir (1000 mg t.i.d.). Doses were adjusted according to the level of renal function. The D+R- patients were also given CMV immune globulin biweekly for 16 weeks. Surveillance blood cultures were obtained at transplantation, at months 1, 2, 3, and 6, and when clinically indicated. The primary study end points were time to CMV infection and disease the first 6 months after transplantation.
                The mean follow up was 14.4 months. Both agents were well tolerated, and no drug interruptions for toxicity occurred. CMV was isolated in 14 of 39 (35.9%) acyclovir-treated and 1 of 40 (2.5%) ganciclovir-treated recipients by 6 months (P=0.0001). Symptomatic CMV disease occurred in 9 of 14 (64%) of the acyclovir patients, two with tissue-invasive disease. Infection rates for acyclovir vs. ganciclovir, respectively, stratified by CMV serology were: D+R-, 54 vs. 0%, P=0.0008; D+R+, 43 vs. 6.6%, P=0.01; D-R+, 8.3 vs. 0%, P=NS. No patient developed CMV infection while taking oral ganciclovir, however three delayed infections occurred 2-7 months after finishing therapy. Each patient had been previously treated for acute rejection.
                Oral acyclovir provides effective CMV prophylaxis only for recipients of seronegative donor kidneys. Oral ganciclovir is a superior agent providing effective CMV prophylaxis for recipients of seropositive donor kidneys. Recipients who are treated for acute rejection are at risk for delayed CMV infection during the first posttransplantation year. To assess the efficacy of high-dose oral acyclovir therapy compared with preemptive, short-course ganciclovir therapy (administered only if cytomegalovirus [CMV] shedding occurred) to prevent CMV disease in liver transplant recipients.
                A randomized controlled trial.
                Liver transplant center at a university-affiliated Veterans Affairs Medical Center.
                47 consecutive patients having liver transplantation.
                Patients were stratified by their CMV antibody status and the CMV antibody status of the donor and were randomly assigned to one of two treatment groups. Surveillance cultures for CMV (buffy coat and urine) were done every 2 to 4 weeks for 24 weeks in all patients. One group received high-dose oral acyclovir (800 mg four times daily). The experimental group received no acyclovir, but if surveillance cultures were positive, ganciclovir (5 mg/kg intravenously twice daily) was administered for 7 days.
                Cytomegalovirus shedding and CMV disease were measured in the two groups.
                Cytomegalovirus shedding before the onset of CMV disease occurred in 25% (6 of 24) of patients in the acyclovir group compared with 22% (5 of 23) in the experimental group. Cytomegalovirus disease developed in 29% (7 of 24) of the acyclovir group and in 4% (1 of 23) of the experimental group (P < 0.05). No hematologic toxicity occurred with ganciclovir.
                Oral acyclovir is ineffective prophylaxis against CMV in liver transplant recipients. Preemptive, short-course ganciclovir therapy in patients with CMV shedding was well tolerated and provided effective prophylaxis against subsequent CMV disease; this protocol targets the patients at risk for CMV disease and minimizes toxicity and expense. A controlled trial of oral acyclovir in herpetic dendritic corneal ulcers was carried out on 31 patients. All patients received minimal wiping debridement of the ulcer, following which they were randomly allocated to receive either oral acyclovir or placebo for 7 days. At the end of treatment 67% of dendritic ulcers in patients receiving acyclovir had healed compared with 43% in placebo recipients. The proportion of ulcers healed in the 2 groups at 7 days showed no significant difference (p = 0.18), but the rate of healing was significantly faster in acyclovir group (p = 0.03). Optimal prophylaxis against cytomegalovirus (CMV) disease for organ transplant patients at risk for primary infection (donor seropositive, recipient seronegative, D+R-) remains to be determined. We hypothesized that prolonged oral ganciclovir therapy following intravenous therapy would provide increased protection.
                A total of 155 evaluable D+R- organ transplant recipients from 13 transplant centers were entered into the study: all received intravenous ganciclovir (5 mg/kg/day) for 5-10 days and then either oral acyclovir (400 mg tid) or oral ganciclovir (1 g tid) for an additional 12 weeks. Patients were assigned to their treatment groups at a central randomization site, with a separate randomization scheme for each of the organs transplanted (kidney, heart, or liver). In the case of kidney transplants, the patients were stratified according to source of the kidney (living related vs. cadaveric donor). The primary endpoint was the incidence of CMV disease in the first six months post-transplant.
                Treatment with oral ganciclovir was associated with a significant decrease in the incidence of symptomatic disease or viremia when compared with the oral acyclovir group (32% vs. 50%, P<0.05). This difference was most marked in terms of tissue invasive disease: only 3 of 15 symptomatic patients in the ganciclovir group vs. 10 of 21 in the acyclovir group developed tissue-invasive infection (P<0.05). There was a significant difference in the time to CMV disease or viremia in the two groups: mean time 212+/-17 days post-transplant for the acyclovir group vs. 291+/-13 days for the ganciclovir group (P<0.001). The incidence of allograft rejection was 34% in the ganciclovir group and 46% in the acyclovir group (P=NS). Leukopenia was more common in the ganciclovir group (P<0.05), but in no case did it require drug discontinuation. Ganciclovir resistance did not develop in this study.
                Prophylaxis with oral ganciclovir following a brief course of intravenous ganciclovir provides useful protection against primary CMV disease. Cytomegalovirus disease is an important cause of morbidity following liver transplantation. To date there has not been an effective prophylaxis for CMV disease after liver transplantation. One hundred forty-three patients were randomized to receive either high dose oral acyclovir (800 mg 4 times a day) alone for 3 months after transplantation (acyclovir group) or intravenous ganciclovir (5 mg/kg twice a day) for 14 days followed by high dose oral acyclovir to complete a 3-month regimen (ganciclovir group). Of 139 patients available for evaluation, 43 of 71 (61%) patients from the acyclovir group developed CMV infection compared with 16 of 68 (24%) from the ganciclovir group (relative risk, 3.69; 95% confidence interval, 2.07-6.56; P < 0.00001). Of those randomized, CMV disease was seen in 20 (28%) of the acyclovir group compared with 6 (9%) of the ganciclovir group (relative risk, 5.11; 95% confidence interval, 2.05-12.75; P = 0.0001). The median time to onset of CMV infection was 45 days in the acyclovir group compared with 78 days in the ganciclovir group (P = 0.004). The median time to onset of CMV disease was 40 days in the acyclovir group compared with 78 days in the ganciclovir patients (P = 0.02). With respect to primary CMV infection, there was no difference in the rates in the 2 groups, but tissue invasive disease and recurrent CMV disease were less frequent in the ganciclovir group. It is concluded that a course of 2 weeks of ganciclovir immediately after transplantation followed by high dose oral acyclovir for 10 weeks is superior to a 12-week course of high dose oral acyclovir alone for prevention of both CMV infection and CMV disease after liver transplantation. However, the lack of significant effect in seronegative recipients who received grafts from seropositive donors suggests that other strategies are needed to prevent CMV infection in this high risk population. An open, prospective, randomised study was conducted to compare the safety and efficacy of valacyclovir vs. oral ganciclovir for cytomegalovirus (CMV) prophylaxis in renal transplant recipients. Eighty-three renal transplant recipients were assigned randomly to receive valacyclovir (n=43) or oral ganciclovir (n=40) for the first 3 months after transplantation. Both groups were similar in terms of demographics, primary renal disease, graft source, HLA matching, immunosuppressive therapy and donor-recipient CMV antibody status. CMV infection was diagnosed by detection of virus DNA in plasma with the Amplicor CMV Test. CMV disease was observed in only one patient belonging to the ganciclovir group, who developed enterocolitis 6 months post-transplantation. No difference was observed between the two treatment groups with respect to detection of CMV DNA, virus infections other than CMV, acute rejection episodes, and serum creatinine levels at 3 and 6 months following transplantation. An increased number of bacterial infections was noted in the ganciclovir group (p 0.003). No adverse reactions with either treatment were reported. The estimated cost of valacyclovir treatment was 20% higher than that of ganciclovir treatment. Overall, both valacyclovir and oral ganciclovir were found to be effective and safe for CMV prophylaxis in renal transplant recipients. Decisions regarding prophylactic regimens should include additional criteria, such as cost or possible development of resistance. A randomized trial was performed to compare the sequential use of 2 weeks of intravenous ganciclovir (10 mg/[kg.d]) followed by 50 weeks of high-dose oral acyclovir (800 mg/m2 four times daily) with 2 weeks of intravenous ganciclovir alone as prophylaxis for cytomegalovirus (CMV) and Epstein-Barr virus (EBV) disease after pediatric liver transplantation. CMV disease was diagnosed for seven of 24 patients treated with ganciclovir followed by high-dose oral acyclovir compared with two of 24 children treated with ganciclovir alone (P = .048). Similarly, the rate of CMV disease among high-risk patients (CMV-positive donor/CMV-negative recipient) treated with the combination regimen was higher than that among high-risk patients treated with ganciclovir alone (four [57%] of seven vs. zero of five, respectively; vs P < .05). The rate of EBV disease among patients treated with the combination regimen (eight [33%] of 24) was similar to that among patients treated with ganciclovir alone (five [21%] of 24; P = not significant). We conclude that sequential prophylaxis with 2 weeks of intravenous ganciclovir followed by 50 weeks of high-dose oral acyclovir did not decrease the frequency of CMV or EBV disease after pediatric liver transplantation when compared with 2 weeks of intravenous ganciclovir alone. Cytomegalovirus disease occurs frequently after solid organ transplantation and has been associated with decreased patient and allograft survival. We hypothesized that CMV transmission or reactivation begins immediately or soon after transplantation, and that a short-duration ganciclovir (GCV)-based regimen would obviate the need for long-term antiviral agent administration, perhaps serving to interdict CMV infection and disease as well as, or perhaps even more effectively than, a more prolonged, oral acyclovir (ACV)-based form of prophylaxis. A total of 311 patients were stratified according to allograft type, age, and presence or absence or diabetes mellitus, and were then randomized to receive either long-duration ACV prophylaxis (800 mg orally or 400 mg i.v. q.i.d. for 12 weeks after transplantation or 6 weeks after any antirejection therapy) versus short-duration GCV (5 mg/kg/12 hr i.v. for 7 days after transplant or after any antirejection therapy) plus human immune globulin (HIg; Sandoglobulin or Minnesota CMV immune globulin) 100 mg/kg i.v. administered on days 1, 4, and 7 after transplant or after any antirejection therapy. A total of 266 patients (ACV, n = 133; GCV+HIg, n = 133) completed the protocol and were available for follow-up. CMV disease occurred in fewer patients (n = 28, 21.0%) in the ACV group, while significantly more patients (n = 42, 31.6%) in the GCV + HIg group developed group developed CMV disease slightly later (2.83 +/- 0.70 months) than those who received GCV/HIg (2.15 +/- 0.21 months, P > 0.01). Multivariate analysis demonstrated (2.15 +/- 0.21 months, P > 0.1). Multivariate analysis demonstrated that receiving antirejection therapy, a liver transplant, or a donor organ from a CMV-seropositive individual if the recipient was CMV seronegative were major risk factors for the development of CMV disease (P < 0.001), while the difference between ACV versus GCV + HIg prophylaxis was also significant (P = 0.054). No differences in actuarial patient or allograft survival, however, were noted between the 2 prophylaxis groups. Overall, ACV prophylaxis appeared to be more effective in reducing the incidence of posttransplant CMV disease, although this effect was diminished in high-risk groups of patients. Our findings indicate that CMV transmission or reactivation may best be prevented by long-term antiviral agent administration, and that the primary morbidity of CMV disease is the need for rehospitalization when either prolonged ACV or short-duration GCV + HIg prophylaxis is used in this patient population. In an attempt to modify the sequelae of cytomegalovirus (CMV) infections after lung transplantation, 25 allograft recipients were randomized to either ganciclovir 5 mg/kg once a day 5 d/wk (Group G) or acyclovir 800 mg four times a day (Group A). All subjects received ganciclovir during postoperative Weeks 1 through 3, and they were then given either A or G regimens until Day 90. At termination of study enrollment, the cumulative incidence of all CMV infections (including seroconversions) was increased in Group A compared with that in Group G (75% versus 15%, p < 0.01), as was the incidence of overt CMV shedding and/or pneumonitis (50% versus 15%, p < 0.043). In comparison with those in Group G, subjects in Group A were also afflicted with an increased prevalence of obliterative bronchiolitis (OB) during the first year after transplantation (54% versus 17%, p < 0.033). Intravenous catheters for ganciclovir administration resulted in four complications among three of the subjects in Group G (23%). The short-term benefits of ganciclovir were ultimately limited, moreover, in that cumulative rates of CMV and prevalence of OB are now similar in both treatment groups after approximately 2 yr of observation. We conclude that prolonged ganciclovir prophylaxis decreases the early incidence of CMV and OB among lung transplant recipients, but these effects are of finite duration. Although CMV prevention appears to have considerable potential value in this population, definitive viral prophylaxis will require development of protracted or repeated treatment regimens, or longer-acting agents. To assess the efficacy of acyclovir and intravenous immune globulin (IVIG) for cytomegalovirus (CMV) prophylaxis in high-risk recipients of solid organ transplants.
                We randomized 21 CMV-seronegative organ transplant recipients with seropositive donors (D+R-) to receive oral acyclovir, 800 mg four times daily, or, in addition to acyclovir, IVIG, 300 mg/kg, every 2 weeks for six doses. Patients were followed closely for the development of CMV infection and disease.
                All but one prophylactically treated patient (95%) developed CMV infection. Fifteen of 21 patients (71%) who received prophylaxis fulfilled criteria for CMV disease. Disease onset was delayed in those who received IVIG, but this did not reach statistical significance. Ganciclovir was used for treatment in 15 of the 21 patients (71%).
                Acyclovir, with or without IVIG, did not prevent primary CMV infection or disease in D+R- solid organ transplant recipients at our institution. Moreover, most patients were treated with ganciclovir despite the use of prophylaxis. Given the ready availability of ganciclovir to treat CMV disease, we recommend a reappraisal of the role of CMV prophylaxis by these means in the solid organ transplant population. In a double-blind controlled study, oral acyclovir has been compared to a placebo in a series of 39 consecutive patients undergoing bone marrow transplantation. A dose of 200 mg was given every 6 h from day 8 to day 35 after transplantation. Pharmacokinetic studies have shown the good absorption of the drug despite intestinal damage related to chemoradiotherapy or gut graft-versus-host disease (GVHD); there was no sign of toxicity. The protection against herpes simplex virus (HSV) infection was complete in the treated group when compared to the control group even in patients with high anti-HSV antibody titres. The same protection was observed against cytomegalovirus (CMV) infection. The incidence of HSV and CMV was the same in both groups after treatment ended. This study confirms the efficacy of acyclovir against HSV infection and possibly against CMV infection when it is given prophylactically after bone marrow transplantation. Despite the use of vidarabine, herpes simplex virus (HSV) infection in neonates continues to be a disease of high morbidity and mortality. We undertook a controlled trial comparing vidarabine with acyclovir for the treatment of neonatal HSV infection.
                Babies less than one month of age with virologically confirmed HSV infection were randomly and blindly assigned to receive either intravenous vidarabine (30 mg per kilogram of body weight per day; n = 95) or acyclovir (30 mg per kilogram per day; n = 107) for 10 days. Actuarial rates of mortality and morbidity among the survivors after one year were compared overall and according to the extent of the disease at entry into the study (infection confined to the skin, eyes, or mouth; encephalitis; or disseminated disease).
                After adjustment for differences between groups in the extent of disease, there was no difference between vidarabine and acyclovir in either morbidity (P = 0.83) or mortality (P = 0.27). None of the 85 babies with disease confined to the skin, eyes, or mouth died. Of the 31 babies in this group who were treated with vidarabine and followed for a year, 88 percent (22 of 25) were judged to be developing normally after one year, as compared with 98 percent (45 of 46) of the 54 treated with acyclovir (95 percent confidence interval for the difference, -4 to 24). For the 71 babies with encephalitis, mortality was 14 percent with vidarabine (5 of 36) and with acyclovir (5 of 35); of the survivors, 43 percent (13 of 30) and 29 percent (8 of 28), respectively, were developing normally after one year (95 percent confidence interval for the difference, -11 to 39). For the 46 babies with disseminated disease, mortality was 50 percent (14 of 28) with vidarabine and 61 percent (11 of 18) with acyclovir (95 percent confidence interval for the difference, -20 to 40); of the survivors, 58 percent (7 of 12) and 60 percent (3 of 5), respectively, were judged to be developing normally after one year (95 percent confidence interval for the difference, -40 to 50). Both medications were without serious toxic effects.
                In this multicenter, randomized, blinded study there were no differences in outcome between vidarabine and acyclovir in the treatment of neonatal HSV infection. The study lacked statistical power to determine whether there were sizable differences within the subgroups of those with localized HSV, encephalitis, or disseminated disease. Bromovinyldeoxyuridine is a potent and safe antiherpes compound that in combination with a placebo treatment promoted the partial and complete healing of herpetic epithelial disease in 22 patients in average times of 4-6 days and 8.5 days respectively. However, when BVDU was combined with 1.5 X 10(6) IU of recombinant a 2C interferon, partial and complete healing times for keratitis in 19 patients were reduced to 2-6 days and 4-6 days respectively. No toxic effects of the medications were observed in any patient. We compared the efficacy and safety of valganciclovir with those of oral ganciclovir in preventing cytomegalovirus (CMV) disease in high-risk seronegative solid organ transplant (SOT) recipients of organs from seropositive donors (D+/R-). In this randomised, prospective, double-blind, double-dummy study, 364 CMV D+/R- patients received valganciclovir 900 mg once daily or oral ganciclovir 1000 mg three times a day (tid) within 10 days of transplant and continued through 100 days. CMV disease, plasma viremia, acute graft rejection, graft loss and safety were analyzed up to 6 and 12 months post-transplant. Endpoint committee-defined CMV disease developed in 12.1% and 15.2% of valganciclovir and ganciclovir patients, respectively, by 6 months, though with a difference in the relative efficacy of valganciclovir and ganciclovir between organs (i.e. an organ type-treatment interaction). By 12 months, respective incidences were 17.2% and 18.4%, and the incidence of investigator-treated CMV disease events was comparable in the valganciclovir (30.5%) and ganciclovir (28.0%) arms. CMV viremia during prophylaxis was significantly lower with valganciclovir (2.9% vs. 10.4%; p=0.001), but was comparable by 12 months (48.5% valganciclovir vs 48.8% ganciclovir). Time-to-onset of CMV disease and to viremia were delayed with valganciclovir; rates of acute allograft rejection were generally lower with valganciclovir. Except for a higher incidence of neutropenia with valganciclovir (8.2%, vs 3.2% ganciclovir) the safety profile was similar for both drugs. Overall, once-daily oral valganciclovir was as clinically effective and well-tolerated as oral ganciclovir tid for CMV prevention in high-risk SOT recipients. Intravenous acyclovir was evaluated in the treatment of 97 immunocompromised patients with mucocutaneous herpes simplex virus infection in a randomized, double-blind, placebo-controlled trial. Acyclovir recipients had significantly shorter periods of virus shedding (p less than 0.0002) and lesion pain (p less than 0.01), and more rapid lesion scabbing (p less than 0.004) and lesion healing (p less than 0.04). The most common adverse reaction was a low incidence of peripheral vein irritation; no serious toxicity could be definitely attributed to acyclovir treatment even in these seriously ill patients. Intravenous acyclovir offers both safe and effective treatment for mucocutaneous herpes simplex virus infection in the immunocompromised host. Idoxuridine which was first used in 1960 (Kaufman et al., 1962), has been for many years the only antiviral agent available in the treatment of herpetic keratitis. It is however no more successful than is mechanical removal of diseased epithelium (Patterson & Jones, 1967), and furthermore it may give rise to serious toxic side effects. The search for an alternative medication is therefore a pressing one. Trifluorothymidine (F3T) has, in recent years, been shown to be more effective than IDU and to be free from significant toxicity. Both of these drugs are pyrimidine nucleosides. Adenine Arabinoside or Arabinoside-A (Ara-A) is, by contrast, a purine nucleoside. It is thought to exert its antiviral effect by blocking DNA polymerase and ribonucleotide reductase. Both oral ganciclovir and valacyclovir decrease the incidence of cytomegalovirus (CMV) disease after renal transplantation. Moreover, valacyclovir has been shown to reduce the risk of acute rejection. Our study was designed to compare the efficacy and safety of oral ganciclovir and valacyclovir in the prophylaxis of CMV disease after renal transplantation.
                A total of 83 patients were prospectively randomized to 3-month treatment with oral ganciclovir (3 g/day, n=36, GAN) or oral valacyclovir (8 g/day, n=35, VAL). A control group (DEF, n=12) was managed by deferred therapy.
                No differences were found in demography, immunosuppression, or donor/recipient CMV serology. The 12-month incidence of CMV disease was 67% in the DEF group compared with 6% in the GAN group and 3% in the VAL group (P<0.001 GAN or VAL vs. DEF; P=0.575 GAN vs. VAL). The biopsy-confirmed acute rejection rate at 12 months was 12% in the VAL group compared with 34% in the GAN group (P=0.030) and 58% in the DEF group (P<0.001). The difference between the GAN and DEF groups was not significant (P=0.087). The average CMV-associated costs per patient were $3,072, $2,906, and $4,906 in the GAN, VAL, and DEF groups, respectively.
                Valacyclovir and oral ganciclovir are equally effective in the prevention of CMV disease after renal transplantation. Both regimens are cost-effective. Valacyclovir is associated with a significantly reduced risk of acute rejection compared with both ganciclovir prophylaxis and deferred therapy. To evaluate the efficacy of oral acyclovir in preventing stromal keratitis or iritis in patients with epithelial keratitis caused by herpes simplex virus (HSV).
                Patients with HSV epithelial keratitis of 1-week or less duration were treated with topical trifluridine and were randomly assigned to receive a 3-week course of oral acyclovir, 400 mg 5 times a day (hereafter referred to as the acyclovir group), or placebo (hereafter referred to as the placebo group). The development of HSV stromal keratitis or iritis was assessed during 12 months of follow-up.
                Stromal keratitis or iritis developed in 17 (11%) of the 153 patients in the acyclovir group and in 14 (10%) of the 134 patients in the placebo group. Compared with the placebo group, the adjusted rate ratio for the development of stromal keratitis or iritis in the acyclovir group was 1.16 (95% confidence interval, 0.56-2.43). The development of stromal keratitis or iritis was more frequent in patients with a history of HSV stromal keratitis or iritis than in those without such a history (23% vs 9%; P = .01).
                For patients with HSV epithelial keratitis treated with topical trifluridine, no apparent benefit of a 3-week course of oral acyclovir in preventing HSV stromal keratitis or iritis was seen during the subsequent year. The 1-year rate of development of stromal keratitis or iritis was lower than previously reported in the literature, except in patients with a history of HSV stromal keratitis or iritis. 46 patients with acute herpes zoster ophthalmicus of less than 72 hours duration were recruited into a placebo controlled trial to assess the efficacy of oral acyclovir, 800 mg 5 times daily, in preventing or modifying ocular complications and pain. Fewer acyclovir recipients developed intraocular complications and these were less severe but neither difference was statistically significant. However, active ocular disease was significantly less common in the acyclovir group (p = 0.01) at 6 months. Pain was significantly less severe in the acyclovir group between 2 and 6 months. The proportion of patients with pain scores greater than 0 was significantly lower in the acyclovir group between 2 and 3 months. Oral acyclovir appears to modify the disease process in herpes zoster ophthalmicus, to reduce the severity and incidence of postherpetic pain and especially to protect against long-term ocular complications. The tolerability and efficacy of epidermal growth factor (EGF) in the topical treatment of herpetic corneal ulcers in addition to topical acyclovir have been evaluated in a double-blind, placebo-controlled, randomized study in two groups of patients. The time required for complete reepithelialization of the cornea was recorded, and the data obtained were analyzed statistically. In the EGF group, the reepithelialization was significantly faster than in the control group. Tolerability of EGF was always excellent. These results indicate that EGF is safe and effective in reducing the healing time of herpetic corneal ulcers. Despite current approaches to prophylaxis, cytomegalovirus (CMV) continues to be a common cause of infection and disease in solid-organ-transplant patients. Thus, we conducted a controlled trial comparing long-term administration of ganciclovir with high-dose acyclovir for prevention of CMV infection and disease in liver transplant recipients. At the time of transplant, patients were randomised to receive either ganciclovir (6 mg/kg body weight per day intravenously from postoperative day 1 to day 30, then 6 mg/kg per day Monday through Friday until day 100) or acyclovir (10 mg/kg intravenously every 8 h from postoperative day 1 to day of discharge, then 800 mg orally four times a day until day 100). Patients were followed for development of CMV infection, CMV disease, and drug-related toxicity by frequent cultures, serological tests, laboratory measurements, and tissue biopsies. During the first 120 days after transplant, CMV infection occurred in 48 of 126 (38%) acyclovir patients but in only 6 of 124 (5%) ganciclovir patients (p < 0.0001). Similarly, symptomatic CMV disease developed in 12 of 126 (10%) acyclovir patients but in only 1 of 124 (0.8%) ganciclovir patients (p = 0.002). Ganciclovir reduced the incidence of CMV infection in both CMV antibody positive (37 vs 4%, p = 0.001) and negative patients (42 vs 11%, p = 0.06). In a multivariate analysis of donor-recipient CMV antibody status and other risk factors, prophylactic ganciclovir was the most significant factor protecting against CMV infection (p < 0.0001) and disease (p = 0.001). Ganciclovir and acyclovir were generally well-tolerated. Incidences of leukopenia, thrombocytopenia, renal failure, and other adverse events were similar in the two groups. CMV can be eliminated almost completely as a significant pathogen in liver transplant recipients by the long-term administration of prophylactic ganciclovir. In addition, the treatment is safe. Unlike parenteral gancicovir, the efficacy of oral ganciclovir in the prevention and treatment of cytomegalovirus (CMV) infection in kidney transplantation has not been well documented. This study prospectively evaluated the episodes of CMV infection within the first nine months after transplantation in renal transplant recipients treated prophylactically with oral ganciclovir (750 mg twice a day) over a period of 3 months (oral ganciclovir, N = 22), compared with patients randomly assigned as controls (controls, N = 22) who did not receive any anti-viral prophylaxis. Diagnosis of CMV infection at presentation included serological determination of CMV-specific immunoglobulin M antibodies, CMV immunofluorescence assay [standard culture tube and shell vial] (blood) and virus isolation (urine and tissue). CMV infection occurred in one patient (5%) in the oral ganciclovir group and 6 patients (27%) in the control group (p < 0.05). The episodes of biopsy proven allograft rejections were 5% (1/21) and 18% (4/22) in the oral ganciclovir and control groups, respectively. Except for one, none of these patients developed CMV infection either before or after rejection(s). Controlling for the reason (induction or treatment of rejection) for using cytolytic antibody therapies, we found that prophylactic oral ganciclovir was protective against CMV infection (adjusted risk reduction 0.83; 95% confidence interval, 0.33-0.98; p < 0.05). Neither, the CMV status of donors and recipients nor the treatment for acute rejection had any significant impact on the occurrence of CMV infections. Our results show that oral ganciclovir is an effective and well tolerated therapy in the prevention of CMV infection in renal transplant patients. The optimal prophylactic regimen to prevent cytomegalovirus (CMV) infection and disease in orthotopic liver-transplant patients remains to be established. We tested whether a combination of intravenous ganciclovir (GCV) followed by high dosages of oral acyclovir (ACV) for 4 months provided a higher degree of protection from CMV than oral ACV alone.
                One hundred sixty-seven liver-transplant recipients were randomized to receive 120 days of antiviral treatment starting at the time of transplantation consisting of either ACV 800 mg orally four times daily (n=84) or 14 days of GCV 5 mg/kg intravenously every 12 hr followed by oral ACV 800 mg four times daily (n=83). Prospective laboratory and clinical surveillance was performed to determine primary endpoints (onset of CMV infection and CMV disease) and secondary endpoints (rates of fungal and bacterial infection, allograft rejection, and survival after transplantation). One-year event rates are presented as cumulative percentages.
                During the first year after transplantation, CMV infection developed in 57% of patients treated with ACV and in 37% of patients treated with GCV + ACV (P=0.001). CMV disease developed in 23% of patients treated with ACV and in 11% of patients treated with GCV + ACV (P=0.03). In seronegative recipients of allografts from CMV-seropositive donors (D+/R-), CMV disease developed in 58% of patients treated with ACV and in 25% of patients treated with GCV + ACV (P=0.04). In the D+/R- group, 54% of patients treated with ACV and 17% of patients treated with GCV + ACV developed infection with Candida albicans (P=0.05).
                Prophylaxis of CMV infection in liver-transplant patients with 14 days of intravenous GCV followed by high-dosage oral ACV is more effective than high-dosage oral ACV alone at reducing CMV infection and disease, even for patients in the D+/R- CMV serological group. In a randomized, double-blinded, placebo-controlled trial, we compared the therapeutic effect of oral acyclovir (400 mg five times daily for 10 days) with that of placebo in patients with marrow transplants and culture-proven recurrent mucocutaneous herpes simplex. Twelve patients received acyclovir and nine received placebo. Acyclovir treatment significantly shortened the median duration of viral shedding, new lesion formation, and time to first decrease in pain, resolution of pain, 50% healing, and total healing. These results compared favorably with those previously obtained with intravenous or topical acyclovir preparations. Oral acyclovir is highly effective for the treatment of recurrent mucocutaneous infections caused by herpes simplex virus in immunocompromised patients. Combination antiretroviral therapy administered to HIV-infected individuals has been shown to improve immunologic function and delay the progression of HIV infection. However, because patient adherence to complicated combination-therapy antiretroviral regimens is difficult and because of concerns regarding cumulative toxicity of antiretroviral drugs, regimens that utilize fewer antiretroviral agents are desirable.
                To compare the use three- or four- versus two-drug antiretroviral maintenance regimens following successful induction therapy for HIV infection.
                The following electronic databases were searched for relevant randomized trials or reviews: 1. MEDLINE for the years 1982-1999 using the search terms human immunodeficiency virus, antiretroviral therapy, maintenance therapy, zidovudine, lamivudine, indinavir, stavudine, saquinivir, nelfinavir, didanosine, zalcitabine, ritonovir, AIDS, anti-HIV agents, HIV infection and HIV seropositivity 2. AIDSLINE for the years 1982-1999 using the search terms antiretroviral therapy, maintenance therapy, zidovudine, lamidvudine, indinavir, stavudine, saquinivir, nelfinavir, didanosine, zalcitabine, ritonovir, anti-HIV agents 3. The Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effectiveness and the Cochrane Clinical Trials Register in the Cochrane Library, Issue 2, 1999. 4. The specialist register of trials maintained by the Cochrane Collaborative Review Group on HIV Infection and AIDS 5. AIDSTRIALS, a specialist registry of current and completed trials maintained by the U.S. National Library of Medicine The abstracts of relevant conferences, including the International Conferences on AIDS, the Conference on Retroviruses and Opportunistic Infections, the Infectious Disease Society of America annual meeting and the Interscience Conference on Antimicrobial Agents and Chemotherapy, as indexed by AIDSLINE, were also reviewed. All reference lists of all review articles and primary articles identified were searched.
                Randomized controlled trials in which HIV-infected adults who had successfully completed three- or four-drug antiretroviral induction therapy were randomized to maintenance therapy with three or four drugs or maintenance therapy with two drugs. Successful induction therapy was defined by a plasma viral load of less than 500 copies/ml.
                Two reviewers assessed eligibility and trial quality. Attempts were made to contact the authors of the included abstract. Data on the number of patients experiencing loss of viral suppression were abstracted by two reviewers. The data were pooled, where appropriate, to yield odds ratios, using random effects models.
                Four trials were identified including three published studies and one abstract. Compared to three- or four-drug maintenance therapy, maintenance therapies including fewer drugs were associated with a higher risk of virologic failure (loss of HIV suppression to non-detectable levels). Combining the results of all four studies yielded an odds ratio of 5.55 (95% confidence interval, 3.14 - 9.80). Similar results were obtained when the one abstract was excluded (odds ratio, 5.48; 95% confidence interval, 2.82 - 10.65). Performing subgroup analyses of studies using the same induction and maintenance regimens gave similar results. Maintenance regimens of zidovudine and lamivudine compared to maintenance regimens with zidovuine, lamivudine and indinavir, were associated with significantly higher rates of virologic failure (odds ratio, 4.57; 95% confidence interval, 1.80 - 11.58). Similarly, maintenance regimens that discontinued one or more protease inhibitor after including them in induction therapy were also associated with a significantly higher risk of virologic failure (odds ratio, 6.15; 95% confidence interval, 3.40 -11.10). (ABSTRACT TRUNCATED) Cytomegalovirus (CMV) disease is a frequent cause of serious morbidity after solid-organ transplantation. The prophylactic regimens used to prevent CMV infection and disease have shown limited benefit in seronegative recipients. We studied the safety and efficacy of oral ganciclovir in the prevention of CMV disease following orthotopic liver transplantation.
                Between December, 1993, and April, 1995, 304 liver-transplant recipients were randomised to receive oral ganciclovir 1000 mg or matching placebo three times a day. Seronegative recipients of seronegative livers were excluded. Study drug was administered as soon as the patient was able to take medication by mouth (no later than day 10) until the 98th day after transplantation. Patients were assessed at specified times throughout the first 6 months after surgery for evidence of CMV infection, CMV disease, rejection, opportunistic infections, and possible drug toxicity.
                The Kaplan-Meier estimate of the 6-month incidence of CMV disease was 29 (18.9%) of 154 in the placebo group, compared with seven (4.8%) of 150 in the ganciclovir group (p < 0.001). In the high-risk group of seronegative recipients (R-) of seropositive livers (D+), incidence of CMV disease was 11 (44.0%) of 25 in the placebo group, three (14.8%) of 21 in the ganciclovir group (p = 0.02). Significant benefit was also observed in those receiving antibodies to lymphocytes, where the incidence of CMV disease was 12 (32.9%) of 37 in the placebo group and two (4.6%) of 44 in the ganciclovir group (p = 0.002). Oral ganciclovir reduced the incidence of CMV infection (placebo 79 [51.5%] of 154; ganciclovir 37 [24.5%] of 150; p < 0.001) and also reduced symptomatic herpes-simplex infections (Kaplan-Meier estimates: placebo 36 [23.5%] of 154; ganciclovir five [3.5%] of 150; p < 0.001).
                Oral ganciclovir is a safe and effective method for the prevention of CMV disease after orthotopic liver transplantation. Previous studies showed that the combination of trifluridine with human leukocyte interferon in the treatment of dendritic keratitis is effective, and that the best results were obtained with the highest titer then available (30 X 10(6) IU/mL). The present study was undertaken to see if an even higher titer (100 X 10(6) IU/mL) would be more effective. A statistically significant greater effectiveness of the higher titer could not be verified. To compare the lipid and metabolic effects, efficacy, and safety of twice-daily regimens of Trizivir (abacavir 300 mg/lamivudine 150 mg/zidovudine 300 mg triple nucleoside tablet; TZV), Combivir (lamivudine 150 mg/zidovudine 300 mg combination tablet; COM)+nelfinavir (NFV), and stavudine (d4 T)+lamivudine (3TC)+NFV.
                An international, phase 4, open-label, parallel-group, 34-centre study was conducted in 254 non-diabetic, antiretroviral-naive, HIV-infected out-patients with an HIV-1 RNA level of >1000 HIV-1 RNA copies/mL and < or =200,000 copies/mL and a CD4 cell count of >50 cells/microL.
                Patients were randomized 1 : 1 : 1 to TZV twice daily (n = 85), COM/NFV 1250 mg twice daily (n = 88), or d4T 40 mg+3TC 150 mg+NFV 1250 mg twice daily (n = 81) for 96 weeks. Treatments were compared using analysis of covariance (ANCOVA) with regard to changes from baseline in fasting lipids in the total population and in sex and ethnic subgroups. The proportions of patients achieving HIV-1 RNA <50 and <400 copies/mL were compared using a 95% confidence interval (CI) on the difference between proportions.
                The study population was diverse (50% female, 40% black and 37% Hispanic). Mean baseline low-density lipoprotein (LDL) cholesterol was 99 mg/dL, HIV-1 RNA was 4.43 log10 copies/mL and CD4 cell count was 355 cells/microL. At week 96, fasting LDL cholesterol changed minimally in the TZV group [least square mean (LSM) change from baseline, -8 mg/dL], but increased with d4T/3TC/NFV and COM/NFV (+29 and +19 mg/dL, respectively; P < 0.001 versus TZV). Week 96 LDL-cholesterol levels were significantly lower in the TZV group than in the other two treatment groups in women and men and lower than in the d4T/3TC/NFV group in Hispanic and black patients. In black patients, the week-96 LSM change from baseline in LDL cholesterol was significantly less with TZV than with d4T/3TC/NFV (+1 vs+39 mg/dL; P = 0.003). Total cholesterol >200 mg/dL occurred in a smaller proportion of patients receiving TZV (30%) compared with COM/NFV (50%) or d4T/3TC/NFV (60%; P = 0.005 vs TZV). High-density lipoprotein (HDL) cholesterol did not change markedly with any treatment. Although triglycerides increased, they changed least in women and Hispanic patients receiving TZV. Virological and CD4 responses to the treatments were similar in the total population and in the subgroups. Diarrhoea was reported more often in the NFV arms and nausea in the ZDV arms.
                Over 96 weeks, TZV twice daily has significantly less effect on LDL cholesterol than COM/NFV or d4T/3TC/NFV twice daily, especially in women and black patients, and is associated with similar virological and CD4 responses. To determine the most convenient and least expensive regimen for prevention of recurrent herpes simplex virus (HSV) infection after marrow transplantation, we conducted a randomized, double-blind comparison of intravenous acyclovir 250 mg/m2 and placebo given once daily for four weeks. Six of 14 acyclovir and nine of 13 placebo recipients shed HSV during prophylaxis. All nine culture-positive placebo recipients developed associated lesions during prophylaxis compared to four of six acyclovir recipients. Median time to first culture-positive lesion was significantly delayed by acyclovir compared to placebo (33 days after transplant vs. 10; P = 0.05). Acyclovir-resistant HSV was recovered from one acyclovir recipient while receiving prophylactic acyclovir, and from two placebo recipients during subsequent administration of therapeutic acyclovir. Once-daily intravenous acyclovir can significantly delay time to appearance of culture-positive HSV lesions after marrow transplant, but virological and clinical breakthrough may occur and optimal prevention will require administration of intravenous acyclovir more than once daily. It is common practice to administer acyclovir as prophylaxis to patients with hematologic malignancies during neutropenia; however, effective therapy requires frequent dosing, which is difficult in this setting. Valacyclovir has greater oral bioavailability and requires less frequent dosing.
                To evaluate the efficacy and safety of valacyclovir compared with acyclovir.
                Patients who had been treated with chemotherapy or stem-cell transplantation were randomized to receive acyclovir 400 mg orally 3 times daily (n = 51), valacyclovir 500 mg orally twice daily (n = 48), or valacyclovir 250 mg orally twice daily (n = 52) during neutropenia.
                Clinical success, defined as the absence of an active herpes simplex virus (HSV) lesion or asymptomatic viral shedding, was similar between the 3 groups (acyclovir 96%, valacyclovir 500 mg 95%, valacyclovir 250 mg 100%). The overall rates of adverse events were similar in the 3 groups.
                Prophylactic treatment with valacyclovir is an effective and safe alternative to acyclovir for the prevention of HSV reactivation in patients with hematologic malignancies. Thirty-three patients were followed in a double controlled study to test the efficacy of IDU and TFT on superficial epithelial herpes simplex virus infection. Sixteen received TFT and 17, IDU. There were four failures in patients on IDU therapy and no failures in the 16 patients using TFT. These results indicate a trend for greater efficacy of TFT than IDU. In those patients who healed with IDU and with TFT, there was no difference in the number of days to heal in each group. Oral acyclovir was found to be safe and effective for the prevention of herpes simplex virus reactivation after marrow transplantation in a double-blind, placebo-controlled trial. Acyclovir or placebo was administered to 49 patients for 5 weeks beginning 1 week before transplantation: 5 of 24 patients receiving acyclovir developed herpes simplex virus infection during prophylaxis, compared to 17 of 25 patients receiving placebo (p less than 0.01). The median time to first virus reactivation was significantly longer among patients receiving acyclovir (78 days versus 9 days after transplant, p = 0.006). The effect was even more pronounced when the analysis was adjusted for drug compliance: Among patients taking a minimum of 40% of their prescribed drug, acyclovir was 96% virologically effective and 100% clinically effective during the period of administration. Acyclovir use was also associated with significantly more rapid marrow engraftment in patients receiving methotrexate. No virus resistant to acyclovir was isolated. Oral acyclovir provides effective prophylaxis against reactivation of herpes simplex virus among severely immunosuppressed patients able to take orally administered drugs. One hundred two unselected patients with ulceration of the cornea due to herpes simples virus were treated with either adenine arabinoside or trifluorothymide; the trial was double-blind, stratified, and radomized. The two drugs were given topically five times per day, and the rate of healing was observed and recorded. The series included 87 patients with dendritic ulcers and 15 with amoeboid ulcers. Dendritic ulcers of the cornea can be accurately measured, and the healing process can be easily followed. In this situation no statistically significant difference between the efficacy of adenine arabinoside and that of trifluorothymidine was demonstrated. Amoeboid ulcers are more difficult to evaluate than dendritic ulcers, and their responses to treatment vary considerably; however, data from this small group of patients suggest that trifluorothymodine may be more effective than adenine arabinoside for the treatment of amoeboid ulcers. To assess the safety and efficacy of antioxidant therapy for patients with chronic hepatitis C virus (HCV) infection.
                One hundred chronic HCV infection patients failed in interferon treatment were enrolled and randomly assigned to receive combined intravenous and oral antioxidants or placebo, or oral treatment alone. Primary end points were liver enzymes, HCV-RNA levels and histology.
                Combined oral and intravenous antioxidant therapy was associated with a significant decline in ALT levels in 52% of patients who received antioxidant therapy vs 20% of patients who received placebo (P = 0.05). Histology activity index (HAI) score at the end of treatment was reduced in 48% of patients who received antioxidant therapy vs 26% of patients who received placebo (P = 0.21). HCV-RNA levels decreased by 1-log or more in 28% of patients who received antioxidant therapy vs 12% who received placebo (P = NS). In part II of the trial, oral administration of antioxidants was not associated with significant alterations in any of the end points.
                Antioxidant therapy has a mild beneficial effect on the inflammatory response of chronic HCV infection patients who are non-responders to interferon. Combined antiviral and antioxidant therapy may be beneficial for these patients. The purpose of this study was to analyze different regimens of viral prophylaxis after combined pancreas-kidney transplantation (PKT). Over a 4-year period, we performed 82 PKTs with quadruple immunosuppression with OKT3 induction. Four regimens of prophylaxis were studied. The first 30 patients received standard intravenous immunoglobulin (IVIG; 0.5 g/kg) for 6 doses and oral acyclovir for 3 months. The next 34 recipients received intravenous ganciclovir (2.5 mg/kg) twice daily for 2 weeks followed by oral acyclovir for 3 months. In the third group, patients were randomized to 5 doses over 2 months of either standard IVIG (n = 9) or CMV hyperimmune globulin (Cytogam; n = 9; 100-150 mg/kg) plus 2 weeks of i.v. ganciclovir followed by 3 months of oral acyclovir. The 4 groups were similar with respect to clinical, demographic, and immunologic variables, including donor and recipient CMV serologic status and blood transfusions. All patients were monitored for viral infections in the first 6 months after PKT. The regimens of prophylaxis resulted in (1) no major non-CMV (including no EBV) viral infections; (2) 3 cases of minor non-CMV viral infections (shingles); and (3) no differences in the incidence, timing, or severity of symptomatic CMV infections in the 4 groups. No death or graft loss was due to viral infection. Prophylaxis is effective in reducing the incidence of non-CMV viral infections and may reduce the severity of symptomatic CMV infection. However, we could not show any added benefit of either Cytogam or standard IVIG when used in combination with other antiviral agents. For economic as well as efficacy reasons, we recommended that IVIG preparations not be used routinely with antilymphocyte therapy but only in high-risk situations such as primary CMV exposure. Forty-one patients receiving remission induction chemotherapy with vincristine, adriamycin and prednisolone (VAP) for high grade lymphoma or acute lymphoblastic leukaemia were entered into a double blind, placebo controlled trial of oral acyclovir prophylaxis against herpes simplex virus (HSV) infection. The dose of acyclovir was 200 mg four times daily for the duration of chemotherapy (six weeks). Of the 40 evaluable patients, 20 were randomised to each arm. Prophylactic oral acyclovir significantly reduced the incidence of clinical HSV infection from 60% on placebo to 5% acyclovir (P less than 0.001), and the incidence of viral isolates from 70% on placebo to 5% on acyclovir (P less than 0.001). To evaluate (a) the prophylactic effect of the antiherpetic drug acyclovir on oral ulcers in patients with acute myeloid leukaemia receiving remission induction chemotherapy and thus (b), indirectly, the role of herpes simplex virus in the aetiology of these ulcers.
                Randomised, double blind, placebo controlled trial.
                74 herpes simplex virus seropositive patients aged 18-84. Thirty seven patients received acyclovir (800 mg by mouth daily) and 37 placebo. The patients were examined daily for 28 days.
                Occurrence of herpes labialis, intraoral ulcers, and acute necrotising ulcerative gingivitis.
                The two populations were comparable in age, sex, type of antineoplastic treatment, and history of herpes labialis. Acute oral infections occurred in 25 of the acyclovir treated patients and 36 of the placebo treated patients (relative risk 0.69 (95% confidence interval 0.55 to 0.87)). This difference was due to a reduction in the incidence of herpes labialis (one case versus eight cases; relative risk 0.13 (0.02 to 0.95)), intraoral ulcers excluding the soft palate (one case versus 13 cases; relative risk 0.08 (0.01 to 0.56)), and acute necrotising ulcerative gingivitis (one case versus eight cases; relative risk 0.13 (0.02 to 0.95)). However, ulcers on the soft palate were diagnosed with similar frequency in the two groups. Isolation of herpes simplex virus type 1 in saliva was reduced from 15 cases in the placebo group to one case in the acyclovir group (relative risk 0.07 (0.01 to 0.48)).
                Intraoral ulcers excluding the soft palate are most often due to infection with herpes simplex virus, whereas ulcers on the soft palate have a non-herpetic aetiology. The findings suggest that acute necrotising ulcerative gingivitis may also be due to herpes simplex virus. Prophylaxis with acyclovir should be considered for patients with acute myeloid leukaemia during remission induction therapy. The potential of prophylactic ganciclovir for the control of cytomegalovirus (CMV) infection was evaluated in a prospective controlled trial of 65 patients after liver transplantation. A group of 33 patients received ganciclovir (10 mg/kg/day) during the third and fourth weeks after transplantation, while 32 patients were randomised to receive ganciclovir (10 mg/kg/day) only when clinical CMV disease was diagnosed. Eight patients (25%) in the latter group received ganciclovir and included the only death attributed to CMV infection in the study. Prophylactic ganciclovir was associated with a lower incidence of serologically diagnosed secondary infection and the development of the IgM anti-CMV antibody. However, the frequency of clinical infections was similar in the two groups (9/33 vs. 11/32). Liver function tests during the second month after transplantation were not significantly better in the patients receiving prophylactic ganciclovir. Leucopaenia was not seen in patients receiving prophylactic ganciclovir. nan Treatment with prophylactic oral acyclovir, intravenous ganciclovir, or immunoglobulins to prevent cytomegalovirus (CMV) infection and disease in renal transplantation is associated with variable efficacy and significant expense. We studied control of CMV in renal transplant recipients using either prophylactic oral ganciclovir or deferred therapy with intensive monitoring with polymerase chain reaction (PCR) analysis.
                Forty-two recipients were followed for 6 months after transplantation. Ganciclovir (1000 mg p.o. t.i.d.; n=19) or acyclovir (200 mg p.o. b.i.d.; n=23) was begun at transplantation and continued for 12 weeks. PCR for CMV was performed on buffy-coat specimens every week for 15 weeks and at months 5 and 6.
                No patients in the ganciclovir group, compared with 14 of 23 patients (61%) in the deferred-therapy group (P<0.0001), developed CMV disease during the first 12 weeks. In the ganciclovir group, 4 of 19 patients (21%) subsequently experienced 5 episodes, whereas 14 patients in the deferred-therapy group experienced 18 episodes (P=0.013 for subjects and P=0.026 for episodes). The time to disease was also delayed in the ganciclovir group compared with the deferred-therapy group (133+/-17 days vs. 51+/-7 days; P<0.0001). Oral ganciclovir also prevented CMV viremia during prophylaxis (2/19 patients [11%] vs. 23/23 patients [100%]). Time to CMV viremia was delayed in the ganciclovir group; however, 13/19 patients (68%) ultimately showed PCR evidence for CMV viremia (P=0.005).
                An initial 12-week course of oral ganciclovir prevents CMV disease and infection in renal transplant recipients during prophylaxis, and the benefits persist after discontinuation.
Trifluridine and acyclovir are more effective than idoxuridine or vidarabine and similar in therapeutic effectiveness. Brivudine and ganciclovir are at least as effective as acyclovir. While not improving outcome, the combination of interferon and an antiviral agent may speed healing. The effectiveness of corneal epithelial débridement is improved by an antiviral agent.