Valganciclovir: Recent Progress

Pescovitz, Mark D.

doi:10.1111/j.1600-6143.2010.03112.x

Cited by 11 publications

(5 citation statements)

References 30 publications

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“…Extending anti‐CMV prophylaxis to 6 months appears to provide a significant benefit in reducing the incidence of CMV disease and viraemia in high‐risk D + R − SOT patients, compared to 3 month prophylactic regimens[2,6]. While these results are encouraging, the impact of lengthening prophylaxis on the primary CMV immune response in D + R − SOT patients has not been established, and needs to be evaluated in a prospective clinical trial [9].…”

Section: Discussionmentioning

confidence: 99%

“…Universal antiviral prophylaxis with the orally available agent valganciclovir (VALGAN) has proved successful in limiting cytomegalovirus (CMV) disease, reducing mortality and graft rejection in high‐risk CMV seronegative recipients (R − ) of a solid organ transplant (SOT) from a seropositive donor (D + )[1,2]. Without antiviral prophylaxis, CMV disease occurs with incidence up to 72% in D + R − patients, during the first 3 months post‐transplant, when patients are receiving intensive immunosuppressive agents for prevention of graft rejection [3].…”

Section: Introductionmentioning

confidence: 99%

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Primary response against cytomegalovirus during antiviral prophylaxis with valganciclovir, in solid organ transplant recipients

Rosa

Limaye

Krishnan

et al. 2011

Transplant International

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Antiviral prophylaxis has proved successful for prevention of cytomegalovirus (CMV) disease in solid organ transplant (SOT) patients; though emerging data suggest that antiviral agents interfere with immunity, and may inhibit immune-priming. In this context, we investigated levels and phenotype of primary CMV-specific immune responses that developed during antiviral prophylaxis in a cohort of CMV seronegative recipients (R−) of a SOT from a seropositive donor (D+). We longitudinally monitored CMV viral load, antibodies and levels of the negative immuno-modulator IL-10. PBMC were stimulated with CMV-specific peptide libraries to measure CD137 activation marker on CMV-specific T-cells and levels of PD-1 receptor, which is overexpressed on exhausted T-cells. Unexpectedly, the majority (13/18) of D+R− patients who developed a primary CMV response showed early post-transplant CMV-specific responses, though levels of PD-1 on CMV-specific T-cells remained elevated throughout prophylaxis. A strong inverse association was found between levels of plasma IL-10 and CMV-specific cellular immune responses. Our study suggests that during prophylaxis, subclinical CMV infection might have occurred in the D+R− patients, and primary CMV-specific responses were detected early post-transplant when levels of plasma IL-10 were low. Extended prophylaxis or antiviral treatment did not appear to suppress CMV-specific antibodies or T-cells, which however showed exhaustion phenotypes.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Primary response against cytomegalovirus during antiviral prophylaxis with valganciclovir, in solid organ transplant recipients

Rosa

Limaye

Krishnan

et al. 2011

Transplant International

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“…The only significant side effect reported for prophylaxis with V‐GCV was a reduction in white blood cell count . However, several studies reported a V‐GCV related neutropenia (absolute neutrophil count (ANC) <1000 cells/mL) in both SOT and HSCT ranging from 13 to 23% and a severe neutropenia (ANC <500 cells/mL) from 0 to 7% . Neutropenia seems to be significantly higher in patients in treatment with GCV than V‐GCV, and only isolated cases had to discontinue the V‐GCV treatment because of leukopenia adverse effect.…”

Section: Discussionmentioning

confidence: 99%

Complete remission of VZV reactivation treated with valganciclovir in a patient with total lymphocyte depletion and acute kidney injury after allogeneic bone marrow transplantation

Maximova

Pizzol

Granzotto

et al. 2014

APMIS

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Varicella zoster virus (VZV), a threat for hematopoietic stem cell transplantation (HSCT) recipients, is still one of the most common viral pathogens that affect these patients with a reported incidence ranging between 17% and 50% in the post transplantation period. Valganciclovir (V-GCV), a valine ester pro-drug of GCV orally administrable, has recently shown great activity against CMV infections, but there are no reports of its clinical efficacy against VZV. We here report a case history of a patient with positive serologic test for VZV, who underwent allogeneic HSCT and developed an atypical varicella-like illness. First-line therapy with foscarnet had to be discontinued due rapid development of renal impairment (creatinine: 2.60 mg/dL, urea: 130.6 mg/dL) and therefore was switched to V-GCV. The renal impairment and skin lesions of the patient fully recovered after few days of therapy, even though the patient had complete lymphocyte depletion. This is the first case of a patient with chickenpox-like illness treated successfully with V-GCV.

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“…Since there is no vaccine for HCMV, antiviral drugs constitute the current treatment for CMV infection; the available antiviral drugs include ganciclovir (GCV), valganciclovir, foscarnet, cidofovir and fomivirsen (5,6). However, these antiviral therapies have limited efficacy and a high incidence of side-effects.…”

Section: Introductionmentioning

confidence: 99%

Allitridin inhibits human cytomegalovirus replication in vitro

Zhang

Wang

Xiang

et al. 2013

Molecular Medicine Reports

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Human cytomegalovirus (HCMV) has been associated with a wide spectrum of diseases. There is currently no effective treatment for eliminating the virus. Garlic bulb extract has been reported to possess anti-viral efficacy. This study aimed to investigate the expression of the immediate‑early (IE; ul122 and ul123), early (E; ul54) and late (L; ul83) genes of HCMV as well as the inhibitory effect of allitridin on the transcription levels of these genes. The results indicated that a HCMV gene expression cascade occurred, and that the deletion of IE72 had no influence on the transcription of the ul122 gene, while it led to significant reductions of ul54 and ul83 mRNA expression levels. Additionally, allitridin effectively suppressed the transcription of the HCMV IE, E and L genes; the inhibition rates of the transcription of the ul122 and ul123 genes were higher compared with those of ul54 and ul83 mRNA expression, while the expression of the IE genes was not significantly reduced by ganciclovir (GCV). Our results indicate that the HCMV IE72 deletion mutant strain affects the transcription of the virus downstream gene, allitridin inhibits HCMV infection in vitro, and that the IE genes may be the key target of allitridin in its action against HCMV.

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Valganciclovir: Recent Progress

Cited by 11 publications

References 30 publications

Primary response against cytomegalovirus during antiviral prophylaxis with valganciclovir, in solid organ transplant recipients

Primary response against cytomegalovirus during antiviral prophylaxis with valganciclovir, in solid organ transplant recipients

Complete remission of VZV reactivation treated with valganciclovir in a patient with total lymphocyte depletion and acute kidney injury after allogeneic bone marrow transplantation

Allitridin inhibits human cytomegalovirus replication in vitro

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