V C Emery

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..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...

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

..In contrast, prophylaxis is a high-cost strategy which exposes all patients to potentially toxic drugs, does not facilitate immune priming and leads to the development of late HCMV infection and disease in high-risk patients...

..These studies focus attention on understanding the virological and immunological determinants of enhanced viral replication and its pathological consequences...

..Also discussed is whether the data on the pathological consequences of infection warrant routine screening for these viruses in solid organ transplant recipients...

..We await further investigations to determine whether the immune control of HCMV in the elderly patient is as effective as in the younger adult, and whether this is linked to pathological consequences...

..Many of these compounds have undergone successful phase I clinical trials. There are other compounds which have been identified through drug-screening but are at the earlier stages of development...

..We have conducted a prospective investigation to compare the natural history of HHV-6 and HHV-7 infection with that of CMV after renal transplantation...

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

..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...

..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...

..However, in multivariate analyses, elevated virus load continued to be the predominant risk factor for progression to HCMV disease...

..These findings have implications for the potency, dose, and duration of antiviral chemotherapy needed for the effective treatment of this important human pathogen...

..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...

..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...

..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...

..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...

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..Note..

..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...

..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...

..Overall, our findings provide quantitative biomarkers which can be used in pharmacodynamic assessments of the ability of novel CMV vaccines or antiviral drugs to reduce or even interrupt such transmission...

..The data show that both these parameters have prognostic value in multivariate models and should allow the development of novel patient management strategies...

..Finally, the changing face of CMV disease in the era of highly active antiviral chemotherapy is considered with respect to its impact on the frequency of CMV resistance in the clinic...

..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...

..0003). However, there was no significant difference in the prevalence of anti-vif antibodies in patients stratified according to p24 antigen status. The implications of these findings in the context of HIV replication are discussed...

..The relationship disappeared or was obscured after therapy (R = 0.24, P = 0.30 and R = 0.16, P = 0.50, respectively). Thus, we show that HAART affects the HCV specific humoral immune responses without affecting the HCV RNA level...

..In conclusion, short term CMV viremia does not enhance the replication of HCV after LT, while HCV replication does not alter the replication dynamics of CMV...

..This review will focus on advances in understanding the virus-host interaction and options for the new therapeutic control measures...

..Using such models, a good agreement between experimentally determined viral load and resistance patterns is observed...

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

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

..Together with polymerase chain reaction testing, this technique provides measurable parameters that can be a guide to therapeutic decision making and can form the basis of CMV immunotherapy...

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

..The rapid re-population of wild-type viruses may allow the recycling of antiretroviral drugs prescribed previously...

..At this peak rate of virion production we estimate that every possible single and most double mutations would be created each day...

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

..At present, many of these approaches in transplant recipients have focused on infections such as human cytomegalovirus, but the opportunity to use these examples as proof of concept for other infections is discussed...

..25; P=.01). Adjusting for HIV RNA levels, CD4 cell counts, and the age effect, HCV RNA load >5.90 log(10) copies/mL was predictive of progression to AIDS and all-cause mortality over a period of at least 15 years...

..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...

..abstract:..

..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...

..We aimed to assess the relation between markers of liver function and progression to AIDS and death in individuals with haemophilia infected with HIV-1 and hepatitis C virus...

..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...

..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...

..In this outline we present anti-CMV drugs currently in clinical use and give examples of new molecules under laboratory and clinical development...

..We sought to investigate the impact of different immunosuppressive regimens on human cytomegalovirus (HCMV) incidence and replication dynamics in a cohort of 256 patients after liver transplantation...

..Human immunodeficiency virus (HIV) may influence the outcome and natural history of hepatitis C virus (HCV) infection through an impact on acute HCV-specific T cell responses...

..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...

..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...

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

..This article presents supporting evidence for these recommendations and statements...

..The emerging scenario is that the HCMV genotypes developed in early human populations (or even earlier), becoming established via founder or bottleneck effects, and have spread, recombined and mixed worldwide in more recent times...

..42; 95% CI, 2.87-6.81). Change in cumulative PCR status was informative for the risk of subsequent CMV disease...

..Our results demonstrated that detection of HCMV DNA in placental tissues by DNA amplification provides a specific and sensitive method for diagnosis of intrauterine HCMV infection...

..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...

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

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

..Treatment of infected cells with protease inhibitors also increased viral production. These studies indicate that, in contrast to some enveloped RNA viruses, HCMV does not require the cellular ESCRT machinery to complete its envelopment...

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