Ganciclovir in Treatment of CMV
Ganciclovir treatment of symptomatic congenital cytomegalovirus infection: results of a phase II study
Whitley RJ., Cloud G., Gruber W., Storch GA., Demmler GJ., Jacobs RF., Dankner W., Spector SA., Starr S., Pass RF., Stagno S., Britt WJ., Alford C Jr., Soong S,. Zhou XJ., Sherrill L., FitzGerald JM., Sommadossi JP.
Journal of Infectious Diseases. 175(5):1080-6, 1997 May.
Congenital cytomegalovirus (CMV) infection occurs in approximately 1% of newborns in the United States. A phase II evaluation was done of ganciclovir for the treatment of symptomatic congenital CMV infection. Daily doses of 8 or 12 mg/kg were administered in divided doses at 12-h intervals for 6 weeks. Clinical and laboratory evaluations sought evidence of toxicity, quantitative virologic responses in urine, plasma drug concentrations, and clinical outcome. A total of 14 and 28 babies received 8 and 12 mg/kg/day, respectively. Five additional babies received ganciclovir on a compassionate plea basis. Significant laboratory abnormalities included thrombocytopenia (< or = 50,000/mm3) in 37 babies and absolute neutropenia (< or = 500 mm3) in 29 babies. Quantitative excretion of CMV in the urine decreased; however, after cessation of therapy, viruria returned to near pretreatment levels. Hearing improvement or stabilization occurred in 5 (16%) of 30 babies at 6 months or later, indicating efficacy.
Herpes in HIV/AIDS
The management of herpesvirus infections in individuals with human immunodeficiency virus or AIDS
Antiviral Therapy 2 (Suppl 2): 25-28, 1997
Herpesvirus infections are a known cause of significant morbidity in the immunocompromised host, including those with human immunodeficiency virus (HIV) or AIDS. While acyclovir has been available for some time and provides significant benefit for individuals with herpes simplex and varicella-zoster virus infections, the need for improved therapeutics which address the ever evolving problems associated with antiviral resistance and improved therapies for cytomegalovirus (CMV) retinitis requires special note. Current problems in the management of herpesvirus infections focus, in general, on five specific areas. First, it has been recognized that herpes simplex virus can acquire resistance to acyclovir, particularly with prolonged use. Progressive clinical disease can be encountered in individuals who develop thymidine kinase-altered herpes simplex virus isolates. As a consequence, new and improved therapeutics for herpes simplex virus infections, particularly with novel mechanisms of action, warrant introduction. Secondly, management of CMV retinitis has focused, historically, on the utilization of drugs such as ganciclovir and foscarnet. The recent availability of cidofovir that can be administered intermittently may provide a treatment regimen of greater acceptability to those individuals who suffer from CMV retinitis. Fortunately, severe antiviral drugs are under development that will allow for oral administration. Thirdly, new drugs are becoming available for the treatment of herpes zoster in HIV-infected individuals. Sorivudine has been valuated for the treatment of herpes zoster in individuals with HIV infections. The availability of this drug for targeted patient populations will provide a therapeutic regimen allowing for once daily dosing. Fourthly, the use of anti-herpetic agents, particularly acyclovir, has been employed with antiretroviral therapy in order to potentially decrease associated cofactors (e.g. CMV, human herpes virus (HHIV-6), etc). Finally, the recent discovery of HHV-8 and its association with Kaposi's sarcoma provides unique avenues for further investigation. Improvements in all of these areas will result in improved quality of life for individuals with HIV infection and AIDS.