***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
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    Input: BACKGROUND The aim of this double-blind , placebo-controlled study was to determine whether a prolonged course of low-dose ganciclovir prevented the development of clinical cytomegalovirus disease after heart transplantation . METHODS Fifty-six consecutive patients were stratified into two groups : cytomegalovirus-positive recipients ( n = 40 ) and cytomegalovirus-negative recipients of organs from cytomegalovirus-positive donors ( n = 16 ) . All patients received equine antithymocyte globulin induction for 7 days and maintenance doses of cyclosporine , azathioprine , and prednisolone . Ganciclovir ( 5 mg/kg intravenously ) or matching placebo was given with the premedication , three times weekly for the first 6 weeks after transplantation and for another 2 weeks for each treated rejection episode between 6 and 12 weeks . RESULTS Ganciclovir prophylaxis reduced the actuarial incidence of cytomegalovirus disease from 71 % to 11 % in cytomegalovirus-mismatched patients ( p < 0.01 ) . Ganciclovir prophylaxis did not reduce the incidence of cytomegalovirus disease in cytomegalovirus-positive recipients ( 25 % in both placebo and ganciclovir groups ) but did delay its onset and reduce its morbidity . There were no adverse reactions during ganciclovir administration . Gastritis was the most common clinical manifestation of cytomegalovirus disease . Pneumonitis and myocarditis were seen only in placebo-treated cytomegalovirus-mismatched patients . All patients with clinical cytomegalovirus disease responded to ganciclovir , 10 mg/kg/day for 2 weeks . CONCLUSIONS Prolonged low-dose ganciclovir prophylaxis after heart transplantation reduces the incidence of cytomegalovirus disease in cytomegalovirus-mismatched patients and reduces the morbidity of cytomegalovirus disease in cytomegalovirus-positive recipients The use of postdetection antiviral treatment of cytomegalovirus ( CMV ) as a strategy to prevent infection and disease in solid-organ transplant patients has not been evaluated by placebo-controlled trials . We carried out such a study in 69 patients who had received liver transplants and had positive results of CMV polymerase chain reaction within 8 weeks after transplantation but did not have concomitant CMV infection or disease . These patients were r and omly assigned to receive placebo or oral ganciclovir for 8 weeks . CMV infection developed in 21 % and disease developed in 12 % of placebo recipients ( P = .022 ) , compared with 3 % and 0 % , respectively , among ganciclovir recipients ( P = .003 ) . Similarly , in the placebo arm , 55 % and 36 % of CMV-negative patients who received organs from CMV-positive donors developed CMV infection or disease , respectively ( P = .02 ) , compared with 11 % and 0 % of such patients in the ganciclovir arm ( P < .01 ) . Oral ganciclovir administered on CMV detection by PCR prevents CMV infection or disease after liver transplantation Cytomegalovirus is the most important infectious cause of complications and death in organ transplant recipients . The three major consequences of infection with this virus are cytomegalovirus disease ; superinfection with opportunistic pathogens result ing from host defects caused by the virus ; and allograft injury [ 1 , 2 ] . The interaction of the following three factors determines whether cytomegalovirus disease develops in a transplant recipient infected with cytomegalovirus : 1 ) whether the donor and donor organ or the recipient , or both , harbor latent virus that can be reactivated after transplant [ 1 ] ; 2 ) whether the transplant recipient can mount an immune response to the virus [ both cellular and humoral ] ; and 3 ) the type of immunosuppressive therapy administered after transplant [ 4 ] . Transplant recipients in whom primary infection develops at the time of transplant ( donor : cytomegalovirus antibody positive ; recipient : cytomegalovirus antibody negative ) or who test positive for cytomegalovirus antibody before transplantation and require antilymphocyte antibody therapy after transplantation have a greater than 50 % attack rate of cytomegalovirus disease [ 4 ] . Each risk group accounts for 10 % to 20 % of all transplant recipients . Preventing cytomegalovirus disease in these two patient population s is a priority for transplant physicians . Cytomegalovirus disease has been prevented by prolonged administration ( 3 to 4 months ) of antiviral therapies such as acyclovir [ 5 ] , anticytomegalovirus hyperimmune globulin [ 6 ] , or the combination of these two therapies [ 7 ] . These prophylactic strategies reduce the attack rate of cytomegalovirus disease , but this benefit is attenuated in patients who receive antilymphocyte antibody therapy [ 1 ] . Because the risk for developing cytomegalovirus disease depends on the type of immunosuppression administered after transplantation , we have proposed an alternative approach to preventing cytomegalovirus disease . This approach targets patients at greatest risk for cytomegalovirus disease for treatment with the most potent anticytomegalovirus therapy available . The antiviral therapy is administered when the risk is greatest ( for example , during treatment with antilymphocyte antibodies ) . To distinguish this approach from preventive strategies used in all patients ( nontargeted prophylaxis ) , we introduced the term preemptive therapy [ 8 ] . Preliminary studies suggested that ganciclovir administered as preemptive therapy to patients receiving antilymphocyte antibodies might reduce the attack rate of cytomegalovirus disease in transplant recipients who are positive for cytomegalovirus antibody . This multiinstitutional , r and omized clinical trial was design ed to assess the efficacy and safety of preemptive ganciclovir therapy in preventing cytomegalovirus disease in transplant recipients who are positive for cytomegalovirus antibody and who are receiving antilymphocyte antibodies . Methods Patients Consecutive renal transplant recipients who tested positive for cytomegalovirus antibody and who received a kidney from cytomegalovirus antibody-positive or antibody-negative donors at Albany Medical Center , Emory University Hospital , Massachusetts General Hospital , New Engl and Medical Center , University of Chicago Medical Center , and Yale-New Haven Hospital were eligible for enrollment in the study . Patients were r and omly assigned to receive either preemptive ganciclovir or no ganciclovir every day that antilymphocyte antibody therapy ( muromonab-CD3 [ OKT3 ] , antithymocyte globulin , or antilymphocyte globulin ) was administered . Separate r and omization lists were used in each transplantation center ; within each center , separate r and omization lists were used for cadaveric and living , related donors . The investigators at each site knew which patients received the study drug and which patients received no anticytomegalovirus therapy . The cytomegalovirus antibody status of donors and recipients was determined using enzyme immunoassay on recipient serum obtained before transplantation and on donor serum obtained before transfusion . Patients were excluded from the study if they were younger than 20 years of age , were pregnant , had received another organ in addition to a kidney , had received any anticytomegalovirus therapy ( defined as more than 1.2 g of acyclovir per day , unselected immune globulin , or cytomegalovirus hyperimmune globulin ) , or refused to give consent . The committees on human experimentation at each institution approved the study . All study participants were observed for the following outcomes during the 6 months after they received antilymphocyte antibodies : 1 ) cytomegalovirus disease ; 2 ) other infectious diseases ; 3 ) and noninfectious diagnoses . Allograft function 6 months after administration of antilymphocyte antibody was recorded as either present ( for those not requiring dialysis ) or absent ( for those receiving dialysis ) . Serum creatinine levels were recorded for all patients with functioning allografts 6 months after antilymphocyte antibody therapy . Patients were evaluated for cytomegalovirus viremia and disease in three ways . First , the virology laboratory at each program tried to isolate cytomegalovirus from buffy-coat specimens at least every month using either centrifugation culture [ 9 ] , conventional culture techniques [ 10 ] , or both . Second , buffy-coat specimens were cultured for cytomegalovirus when any of the following signs , symptoms , or laboratory abnormalities were present : temperature greater than 38 C , leukocyte count less than 3.0 109 cells/L , dyspnea , abdominal pain , or gastrointestinal bleeding . Third , a biopsy specimen was obtained from any abnormal site , and all biopsy specimens were examined histologically for the presence of characteristic cytomegalovirus inclusion bodies and uptake of immunofluorescent-labeled anticytomegalovirus antibodies . Patients with other signs or symptoms suggesting infection ( such as cough , headache , diarrhea , allograft discomfort , or dysuria ) were evaluated using st and ard diagnostic protocol s. At all study sites , the diagnostic protocol included at least a chest radiograph , leukocyte count , renal and liver function tests , two sets of blood cultures , urinalysis , urine culture , and cultures from other potential sites of infection . For patients who did not survive the 6-month observation period , data on the cause and date of death were collected . Definition of Cytomegalovirus Disease Cytomegalovirus disease was defined as either the cytomegalovirus syndrome or tissue-invasive disease developing within 6 months of antilymphocyte antibody therapy or within 1 month of discontinuing immunosuppression after allograft loss . The cytomegalovirus syndrome was diagnosed when both virologic and clinical criteria were met within a 7-day period . Virologic criteria were fulfilled when cytomegalovirus was isolated from a buffy-coat specimen or bronchoalveolar fluid . Clinical criteria were fulfilled when patients had a temperature higher than 38 C [ without antipyretic agents ] for 3 or more consecutive days and within 7 days of two or more of the following : 1 ) leukopenia [ leukocyte count < 3.0 109 cells/L on two consecutive measurements after stopping azathioprine therapy ] ; 2 ) hepatitis [ serum alanine aminotransferase > 1.5 times the upper limit of normal , without serologic evidence of active hepatitis B or hepatitis C virus ] ; 3 ) atypical lymphocytosis [ more than 20 % of leukocytes ] ; and 4 ) pneumonitis ( an abnormal result on chest radiograph and no alternative explanation [ including absence of Pneumocystis carinii in respiratory secretions ] ) . These criteria were modified slightly from those used by other research ers [ 6 ] because isolation of cytomegalovirus from buffy-coat specimens or bronchoalveolar fluid predicts presence of cytomegalovirus disease , whereas isolation of cytomegalovirus from urine and saliva may not [ 11 ] . Tissue-invasive cytomegalovirus disease was diagnosed histopathologically by showing the presence of inclusion bodies characteristic of cytomegalovirus or by an immunochemical stain positive for cytomegalovirus antigens in a biopsy specimen from a lesion or an abnormal site ( gastrointestinal tract , lung , or liver ) . The investigator at each study site made decisions about treating cytomegalovirus disease . Study Drug Administration The study drug was given daily ( or according to the schedule in Table 1 only when the patient already had intravenous access for administration of antilymphocyte antibodies . The study medication was started within 24 hours of the first dose of each course of antilymphocyte antibodies .  Patients receiving the study drug were given ganciclovir infusions based on daily serum creatinine concentrations ( Table 1 ) . Table 1 . Ganciclovir Dosage Schedule according to Daily Serum Creatinine Concentration Leukocyte count , platelet count , and serum creatinine concentration were monitored daily during antilymphocyte antibody therapy in patients who received preemptive ganciclovir therapy and in controls . Sample Size and Statistical Analysis In the primary analysis , the proportion of patients with cytomegalovirus disease  in the two study groups were compared . On the basis of our previous study [ 4 ] , we assumed that cytomegalovirus disease would develop in 60 % of controls . We wanted to enroll 48 patients who could be evaluated in each group ( for a total of 96 ) to detect a decrease in the proportion of patients with cytomegalovirus disease from 60 % ( in controls ) to 30 % or less ( in patients receiving preemptive ganciclovir therapy ) ; that is , we predicted that preemptive ganciclovir treatment would yield a 50 % lower attack rate ( using a two-sided test , = 0.05 and power = 0.8 ) . Initial analyses were done on an 
    Output:
    
Antiviral prophylaxis is associated with a significant reduction in the risk of CMV infection and all-cause mortality in CMV-negative and CMV-positive renal transplant recipients from CMV-positive donors , regard-less of the immunosuppressive treatments used ( evidence from SR ) .
Pre-emptive therapy has been found to be effective in preventing CMV disease but not all-cause mortality in these patients , even if evidence is less satisfactory compared to data on antiviral prophylaxis ( evidence from SR ) .
There is insufficient evidence of conclusive recommendations on treatment of CMV-negative recipients of renal transplants from CMV-negative donors .