P D Griffiths

..This article will briefly summaries which viruses are important following transplantation and outline the evidence-base from randomized controlled clinical trails for the deployment of antiviral drugs to prevent viral diseases...

..Values of viral load correlate with development of end-organ disease and are moderated by pre-existing natural immunity. Our aim was to determine whether vaccine-induced immunity could do likewise...

..We should also ensure that the primary endpoint of a study immunising seronegative women is congenital CMV infection in babies born to those women, not to women in general, because of the large number of babies born to seropositives...

..For debate, we suggest that baseline pre-emptive therapy with oral valganciclovir should be the comparator for new drug evaluation because it is widely used in clinical practice in many groups of transplant patients...

..To identify recent developments in the management of congenital cytomegalovirus infection which continues to exact a heavy toll on the developing central nervous system...

..Potential mechanisms which CMV could use as a cofactor have been described in vitro and potential criteria for assessing cofactor activity in vivo have been proposed...

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..Measuring polyfunctional CD4+ T cells against HCMV early posttransplant may allow targeted intervention to minimize the occurrence and acute and long-term consequences of HCMV replication...

..The transient nature of UL18 gene expression, and the low abundance of the transcript relative to gB were confirmed...

..Peak CMV load in the blood correlates with CMV disease but frequently occurs too late to provide prognostic information...

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..31; P=.005), which is consistent with the presence of a large proportion (70%) of activated (CD38(+)) ppUL83 CD8(+) CTL within the population of HLA class I tetramer-positive cells...

..02). Thus, PCR viremia provides prognostic information about CMV disease in AIDS patients, and valaciclovir showed activity as both a preemptive and prophylactic agent...

..The full clinicopathological significance of the betaherpesviruses may, thus, be greater than is currently appreciated...

..Note..

..Thus, the effect of CMV seropositivity on clinical progression remains significant in this cohort but does not appear to be mediated through an increase in HIV RNA levels...

..Human herpesvirus 6 (HHV-6) and HHV-7 are newer members of the beta-herpesvirinae that can cause febrile illness in young children and are also possible pathogens in the immunocompromised patient...

..CONCLUSIONS: In patients with HCMV DNAaemia, reconstitution of humoral immunity to HCMV gB occurs rapidly following the initiation of HAART. These changes contrast with the patterns observed for anti-HIV humoral immune responses...

..To determine the effect of highly active antiretroviral therapy (HAART) on the natural history of cytomegalovirus (CMV) retinitis...

..Randomised controlled clinical trials of drugs active against cytomegalovirus are needed to investigate whether this virus is a marker or a determinant of HIV disease progression...

..Increasing acyclovir exposure to that achieved with valacyclovir extends benefits of prophylaxis to include impact on graft rejection and opportunistic infections...

..The modeled and experimental data showed excellent agreement over extended time periods (up to 270 days of therapy) and provide a framework to predict the virologic course of patients at therapeutic initiation...

..Gastrointestinal adenovirus excretion occurs at an advanced stage of HIV disease, and is associated with a poor prognosis. We suggest that adenoviruses may contribute to mortality in this population...

..This study did not support a synergistic effect of ganciclovir plus foscarnet in vivo...

..This assay will have significant utility for studying the activation and replication of PCMV and in swine models for allo- and xenotransplantation...

..Multivariable analysis of risk factors for HCMV DNAemia occurring beyond 100 days after transplant were older age, acute GVHD>grade II and a lower CD34 stem cell dose, whereas Campath-1H use was not associated with late HCMV DNAemia...

..In some patients HCMV loads continue to increase after therapy and they experience multiple episodes of replication...

..73 days; P=.63). Preemptive therapy with VGCV provides control of HCMV replication that is comparable to that achieved with preemptive intravenous therapy with GCV...

..CONCLUSIONS: These results show that, if it proves necessary, ganciclovir and cidofovir should be considered as first-line drugs to treat PCMV infections in xenograft recipients...

..8% of UK blood donors. The presence of high HHV-6 viral loads in healthy normal individuals reiterates the need to consider the confounding effect of HHV-6 viral integration in any laboratory diagnosis of HHV-6 infection...

..In the last three years there have been significant advances in the diagnosis and treatment of congenital CMV. We have developed practical evidence based guidelines for the management of congenital CMV...

..After transplantation, patients have impaired immune responses, thereby rendering serology unreliable for diagnostic purposes. Instead, methods which detect the virus directly in clinical material should be used...

..In conclusion, CMV is a prime candidate for eradication from the human population through vaccination...

..Mixed populations of HCMV strains occur in vivo so cloning of these strains is essential if an authentic genotype is to be defined...

..The characteristically high HHV-6 DNA levels in chromosomal integration may confound laboratory diagnosis of HHV-6 infection and should be given due consideration...

..In the future, clinicians should be alert to novel findings of randomized trials that may provide insight into the pathogenesis of these diseases and the contributions made by clinically silent herpesvirus infections...

..Our findings demonstrate that PCMV could be eradicated from pig herds being bred for xenotransplantation and argue that the spleen from donor animals should be examined as part of quality control procedures if clinical trials proceed...

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..Specific examples will be chosen to emphasize basic principles of the development of resistance and readers are referred elsewhere to a summary of resistance in HIV that follows the same principles...

..The controlled clinical trials performed to date will be summarized, together with suggestions about pharmacodynamic evaluations in the future...

..We suggest that the confounding influence of integration be considered in laboratory investigations associating HHV-6 with disease...

..The possibility of using such an approach for selecting women for more rapid or for routine colposcopy appointments in the two groups respectively is discussed...

..New treatments which are safe and potent are urgently needed and should be highly cost-effective when the full clinical impact of this virus is assessed...

..In this setting, real-time polymerase chain reaction applied to blood samples provides a sensitive, rapid, and quantitative diagnostic tool...

..Both of these newer herpesviruses are potentially susceptible to existing and licensed antiherpesvirus drugs...

..This has implications for the understanding of the pathogenesis of HIV-related pulmonary disease...

..Clustering of genes with similar expression profiles implied a shared function, thus revealing possible roles of previously uncharacterized HHV-6B genes...

..HCMV DNA is frequently detected in renal tubular epithelial cells early after renal transplantation, precedes DNAemia and is associated with poor long-term graft function...

..These studies confirm the neurotropism of HHV-6 but do not demonstrate differences in the distribution, variant type or quantity of HHV-6 in brains from patients with MS versus controls...

..The results provide a rationale for evaluating combinations of other HCMV proteins for incorporation into a multi-target DNA vaccine, and for the optimization of adjuvant usage, to elicit enhanced levels of neutralizing antibodies. 2003...

..The case in support of a lack of protein-coding potential in the region between UL105 and UL111A was also strengthened...

..The model accurately predicted the time of disease onset for fever, gastrointestinal disease and pneumonitis but not for hepatitis and retinitis, implying that other factors may be involved in the pathology of these diseases...

..Although the functions of these genes are unknown, sequence comparisons suggest that UL128 encodes a beta-chemokine...

..These features prompt speculation about the roles of these genes in the two virus families...

..If a vaccine schedule can be identified which controls viral load, this will be recommended for a phase II placebo-controlled trial of clinical efficacy. ..