ABSTRACT
Human herpesvirus 6 (HHV-6) infection and disease are serious complications of allogeneic hematopoietic stem cell transplantation (allo-SCT). Ganciclovir (GCV) is effective against HHV-6 in vitro but the antiviral susceptibility of HHV-6 has not been well characterized in vivo. We retrospectively compared the HHV-6 reactivation rate in pediatric allo-SCT recipients with and without GCV prophylaxis. The HHV-6 reactivation rate at 3 weeks after allo-SCT in patients without prophylactic GCV administration was significantly higher than that in those receiving prophylactic GCV (11/28 vs 0/13, P < 0.01). Five of 36 patients without prophylactic GCV showed clinical manifestations including skin rash, interstitial pneumonitis, persistent thrombocytopenia, enterocolitis and thrombotic microangiopathy, respectively. HHV-6-associated symptoms were observed in one of the 13 patients receiving prophylactic GCV. This patient showed fever, diarrhea and graft rejection concomitantly with a sudden increase of HHV-6 DNA copy number. Patients who received GCV for treatment of HHV-6 infection showed an improvement in symptoms and/or decrease of HHV-6 copy number. Thus, GCV is effective for treating HHV-6 disease after allo-SCT in vivo.
Subject(s)
Antiviral Agents/therapeutic use , Ganciclovir/therapeutic use , Hematopoietic Stem Cell Transplantation , Herpesvirus 6, Human/drug effects , Roseolovirus Infections/prevention & control , Child , DNA, Viral/blood , Drug Evaluation , Female , Herpes Zoster/prevention & control , Herpesvirus 6, Human/growth & development , Herpesvirus 6, Human/isolation & purification , Humans , Male , Polymerase Chain Reaction , Retrospective Studies , Roseolovirus Infections/drug therapy , Roseolovirus Infections/epidemiology , Roseolovirus Infections/mortality , Transplantation, Homologous , Viremia/drug therapy , Virus Activation/drug effectsABSTRACT
We report three pediatric patients with ganciclovir-resistant cytomegalovirus (CMV) retinitis who were successfully treated with foscarnet. The patients were recipients of hematopoietic stem cell transplantation (SCT) from HLA-mismatched donors. Because these patients had developed or experienced progressive CMV retinitis during ganciclovir therapy, they received foscarnet therapy at 60 mg/kg every 8 h. Their retinitis resolved promptly after initiating foscarnet therapy, suggesting foscarnet's effectiveness in treating ganciclovir-resistant CMV infection. The amount of CMV mRNA was quantitatively measured using an NASBA technique, which amplified the beta2.7 transcripts specific for CMV replication. This technique was useful for monitoring disease activity in a more rapid and sensitive manner than the PCR assay for CMV DNA.
Subject(s)
Antiviral Agents/administration & dosage , Cytomegalovirus Retinitis/therapy , Drug Resistance, Viral , Foscarnet/administration & dosage , Hematopoietic Stem Cell Transplantation/adverse effects , Adolescent , Child , Cytomegalovirus/genetics , Cytomegalovirus Retinitis/diagnosis , Cytomegalovirus Retinitis/etiology , Female , Ganciclovir/administration & dosage , Humans , Infant , Nucleic Acid Amplification Techniques , RNA, Viral/bloodABSTRACT
Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease resulting from lytic infection of oligodendrocytes by the papovavirus JC (JCV). PML has also been recognized as an AIDS-defining illness. The incidence of PML has increased since 1987 and it occurs in up to 4% of patients with AIDS. To date, there is no treatment available for PML and it usually results in death within 3-6 months of diagnosis. However, there are some reports of remission of PML after antiretroviral therapy. We report a 12-year-old child with hemophilia B and developing AIDS with the onset of PML. With highly active antiretroviral therapy, PML subsided with an increase of CD4 count from 10 to 300/microl in spite of about 1.0 X 10(4) human immunodeficiency virus (HIV)-1-RNA copies. He has survived more than 1 year without specific therapy against JCV. Highly active antiretroviral therapy appears to have improved his prognosis in HIV-associated PML.
Subject(s)
Acquired Immunodeficiency Syndrome/drug therapy , Anti-HIV Agents/therapeutic use , HIV Infections/drug therapy , Leukoencephalopathy, Progressive Multifocal/drug therapy , Acquired Immunodeficiency Syndrome/complications , Acquired Immunodeficiency Syndrome/pathology , Brain/pathology , CD4 Lymphocyte Count , Child , HIV Infections/complications , HIV Infections/pathology , Hemophilia B/complications , Humans , JC Virus/genetics , Leukoencephalopathy, Progressive Multifocal/etiology , Leukoencephalopathy, Progressive Multifocal/pathology , Magnetic Resonance Imaging , Male , Papillomavirus Infections/drug therapy , Papillomavirus Infections/pathology , Reverse Transcriptase Polymerase Chain Reaction , Ritonavir/therapeutic use , Zidovudine/therapeutic useABSTRACT
Human herpesvirus 6 (HHV-6), which belongs to the betaherpesvirus subfamily and infects mainly T cells in vitro, causes acute and latent infections. Two variants of HHV-6 have been distinguished on the basis of differences in several properties. We have determined the complete DNA sequence of HHV-6 variant B (HHV-6B) strain HST, the causative agent of exanthem subitum, and compared the sequence with that of variant A strain U1102. A total of 115 potential open reading frames (ORFs) were identified within the 161,573-bp contiguous sequence of the entire HHV-6 genome, including some genes with remarkable differences in amino acid identity. All genes with <70% identity between the two variants were found to contain deleted regions when ORFs that could not be expressed were excluded from the comparison. Except in the case of U47, these differences were found in immediate-early/regulatory genes, DR2, DR7, U86/90, U89/90, and U95, which may represent characteristic differences of variants A and B. Also, we have successfully typed 14 different strains belonging to variant A or B by PCR using variant-specific primers; the results suggest that the remarkable differences observed were conserved evolutionarily as variant-specific divergence.
