Prevention and Treatment of Cytomegalovirus Disease
Prevention and Treatment of Cytomegalovirus Disease
Cytomegalovirus (CMV) is a ubiquitous herpesvirus that persists indefinitely after primary infection, usually in a latent form in various tissues (e.g., kidney, liver, lung). One percent of newborns are infected with CMV. Transmission of the virus (e.g., in milk or saliva) is common in the perinatal period and early childhood. Transmission also can occur sexually and through blood transfusion and organ transplantation from an infected donor. Approximately 40-90% of adults have antibodies to CMV (i.e., they have been infected with the virus). Primary infection often is asymptomatic in healthy persons, but CMV can cause serious illness in patients who are immunocompromised (e.g., patients with human immunodeficiency virus (HIV) infection or the acquired immunodeficiency syndrome).
CMV is the most common opportunistic infection after solid organ transplantation. The incidence of clinically apparent infection ranges from 20-60%. The mortality rate from CMV infection is as high as 90% if it is left untreated.
CMV disease usually manifests 1-4 months after transplantation or after completion of antiviral prophylactic drug therapy, although some patients are asymptomatic. Primary (direct) effects include a CMV syndrome characterized by a prolonged high fever, fatigue, malaise, anorexia, arthralgias or myalgias, leukopenia, thrombocytopenia, and atypical lymphocytosis.
CMV disease (i.e., CMV syndrome with CMV viremia) may present as infection with signs and symptoms of fever, malaise, leukopenia, or documented CMV invasive disease into organs. CMV disease is classified as being both a tissue invasive problem and a syndrome. CMV infection is the presence of virus as determined by DNA techniques or culture or antigen tests. Tissue-invasive disease often affects the allograft (e.g., mild hepatitis and mild respiratory involvement to severe pneumonitis are common in patients with liver and lung transplants, respectively), although various other organs (e.g., the kidneys, intestines, retinas) may be affected. CMV disease can result in gastroenteritis, which may lead to ulcers and bleeding or perforation of the esophagus, stomach, small intestine, or colon. CMV nephritis may resemble graft rejection. In transplant recipients, retinitis is uncommon. CMV syndrome is often mildly asymptomatic or accompanied by a mononucleosis-like syndrome characterized by fever and neutropenia. Central nervous system involvement (e.g., encephalitis) is uncommon and usually is associated with progressive disease.
CMV infection also can cause secondary (indirect) effects because it suppresses the immune system, which increases the risk of opportunistic infections. Invasive bacterial and fungal superinfection (e.g., Pneumocystis carinii) and septicemia may result. CMV infection may lead to acute and chronic allograft injury and rejection. The virus appears to play a role in arteriosclerosis and rejection after heart transplantation. Cardiac complications (e.g., arrhythmias) also can occur in patients with CMV infection and other types of solid organ transplants. CMV has mutagenic effects, and concerns have been raised about a possible role for the virus in oncogenesis.
The first article describes the impact of CMV prophylactic treatment using oral ganciclovir, an antiviral agent, on the incidence of CMV disease, allograft survival, and costs in solid organ transplant recipients. Factors that influence these outcomes are discussed. The second article addresses the cost savings and other advantages of the oral route of administration for ganciclovir compared with the intravenous route. Data were obtained from patients with HIV infection who were treated for CMV retinitis and a model of hypothetical patients receiving liver transplants and CMV prophylactic drug therapy.
The third article explains the limitations of oral ganciclovir for prophylaxis of CMV disease in solid organ transplant recipients and compares the pharmacology, pharmacokinetics, efficacy, and safety of ganciclovir and valganciclovir, an oral prodrug of ganciclovir, in this patient population. The fourth article lists the criteria for evaluating CMV prophylactic drugs for inclusion in a formulary and compares the advantages and disadvantages of various drugs, including ganciclovir and valganciclovir, using these criteria.
The print version of this article was originally certified for CE credit. For accreditation details, contact the publisher. American Journal of Health-System Pharmacy Inc, 7272 Wisconsin Avenue, Bethesda, MD 20814-4836, phone (301) 657-4383.
Cytomegalovirus (CMV) is a ubiquitous herpesvirus that persists indefinitely after primary infection, usually in a latent form in various tissues (e.g., kidney, liver, lung). One percent of newborns are infected with CMV. Transmission of the virus (e.g., in milk or saliva) is common in the perinatal period and early childhood. Transmission also can occur sexually and through blood transfusion and organ transplantation from an infected donor. Approximately 40-90% of adults have antibodies to CMV (i.e., they have been infected with the virus). Primary infection often is asymptomatic in healthy persons, but CMV can cause serious illness in patients who are immunocompromised (e.g., patients with human immunodeficiency virus (HIV) infection or the acquired immunodeficiency syndrome).
CMV is the most common opportunistic infection after solid organ transplantation. The incidence of clinically apparent infection ranges from 20-60%. The mortality rate from CMV infection is as high as 90% if it is left untreated.
CMV disease usually manifests 1-4 months after transplantation or after completion of antiviral prophylactic drug therapy, although some patients are asymptomatic. Primary (direct) effects include a CMV syndrome characterized by a prolonged high fever, fatigue, malaise, anorexia, arthralgias or myalgias, leukopenia, thrombocytopenia, and atypical lymphocytosis.
CMV disease (i.e., CMV syndrome with CMV viremia) may present as infection with signs and symptoms of fever, malaise, leukopenia, or documented CMV invasive disease into organs. CMV disease is classified as being both a tissue invasive problem and a syndrome. CMV infection is the presence of virus as determined by DNA techniques or culture or antigen tests. Tissue-invasive disease often affects the allograft (e.g., mild hepatitis and mild respiratory involvement to severe pneumonitis are common in patients with liver and lung transplants, respectively), although various other organs (e.g., the kidneys, intestines, retinas) may be affected. CMV disease can result in gastroenteritis, which may lead to ulcers and bleeding or perforation of the esophagus, stomach, small intestine, or colon. CMV nephritis may resemble graft rejection. In transplant recipients, retinitis is uncommon. CMV syndrome is often mildly asymptomatic or accompanied by a mononucleosis-like syndrome characterized by fever and neutropenia. Central nervous system involvement (e.g., encephalitis) is uncommon and usually is associated with progressive disease.
CMV infection also can cause secondary (indirect) effects because it suppresses the immune system, which increases the risk of opportunistic infections. Invasive bacterial and fungal superinfection (e.g., Pneumocystis carinii) and septicemia may result. CMV infection may lead to acute and chronic allograft injury and rejection. The virus appears to play a role in arteriosclerosis and rejection after heart transplantation. Cardiac complications (e.g., arrhythmias) also can occur in patients with CMV infection and other types of solid organ transplants. CMV has mutagenic effects, and concerns have been raised about a possible role for the virus in oncogenesis.
The first article describes the impact of CMV prophylactic treatment using oral ganciclovir, an antiviral agent, on the incidence of CMV disease, allograft survival, and costs in solid organ transplant recipients. Factors that influence these outcomes are discussed. The second article addresses the cost savings and other advantages of the oral route of administration for ganciclovir compared with the intravenous route. Data were obtained from patients with HIV infection who were treated for CMV retinitis and a model of hypothetical patients receiving liver transplants and CMV prophylactic drug therapy.
The third article explains the limitations of oral ganciclovir for prophylaxis of CMV disease in solid organ transplant recipients and compares the pharmacology, pharmacokinetics, efficacy, and safety of ganciclovir and valganciclovir, an oral prodrug of ganciclovir, in this patient population. The fourth article lists the criteria for evaluating CMV prophylactic drugs for inclusion in a formulary and compares the advantages and disadvantages of various drugs, including ganciclovir and valganciclovir, using these criteria.
The print version of this article was originally certified for CE credit. For accreditation details, contact the publisher. American Journal of Health-System Pharmacy Inc, 7272 Wisconsin Avenue, Bethesda, MD 20814-4836, phone (301) 657-4383.
