Resistant Cytomegalovirus Infection Research Articles

The use of sirolimus in ganciclovir‐resistant cytomegalovirus infections in renal transplant recipients

The widespread use of prophylactic ganciclovir and anti-lymphocyte/thymocyte therapies are associated with increased induction of ganciclovir-resistant cytomegalovirus (CMV) strains. The use of sirolimus has been associated with a lower incidence of CMV infection in transplant recipients. We questioned whether it could also be effective as a therapeutic treatment of resistant CMV infection. Patients with ganciclovir-resistant CMV infections determined clinically and by DNA sequencing analysis were enrolled. Antigenaemia and DNA sequencing were used to diagnosis and follow the mutations. Nine transplant patients were given sirolimus plus mycophenolate mofetil (n = 4) or a calcineurin inhibitor (n = 5). Seven out of nine recipients were CMV IgG negative before transplantation. We observed a rapid decrease in antigenaemia levels, reaching zero in eight out of nine (88.9%) patients within a median of 20.3 +/- 10.1 d. Graft function remained stable and no patient presented acute rejection or recurrence of the CMV infection. This suggests that the use of sirolimus plus ganciclovir therapy could be useful in ganciclovir-resistant CMV infections.

Clinical impact of ganciclovir‐resistant cytomegalovirus infections in solid organ transplant patients

Clinical consequences of ganciclovir resistant cytomegalovirus (CMV) infections were studied during 2 large prophylactic trials consisting of 100 days of valganciclovir or ganciclovir prophylaxis in solid organ transplant (SOT) recipients. The first one involved 301 high-risk (CMV donor seropositive/recipient seronegative) SOT recipients excluding lung transplants followed for 12 months, whereas the second one involved 80 lung transplant patients evaluated over 6 months. Among the 7 patients (4 non-lung and 3 lung transplant patients) carrying viruses with known ganciclovir-resistance [corrected] mutations in blood, adverse clinical outcome was only observed in the lung transplant recipients. Additionally, no CMV resistance mutations were observed in non-lung transplant patients receiving valganciclovir.

Treatment of Ganciclovir Resistant Cytomegalovirus Infection with Foscarnet in a Kidney-Pancreas Transplant Patient

Treatment of Ganciclovir Resistant Cytomegalovirus Infection with Foscarnet in a Kidney-Pancreas Transplant Patient

Emergence of UL97 mutations in AIDS patients with CMV infection before or after the introduction of highly active antiretroviral therapy (HAART)

The emergence of resistance to available antiviral drugs may cause higher Cytomegalovirus (CMV)-associated morbidity and mortality in hematopoietic cell transplant (HCT) recipients. Few novel antiviral drugs are being developed with potential effect against refractory or resistant CMV infections. Brincidofovir, an oral nucleotide analog and prodrug of cidofovir, has shown in vitro activity against CMV.We reviewed data of 4 cancer patients with resistant CMV or herpes simplex virus (HSV) infections and were treated with brincidofovir under emergency IND application.Three out of the 4 patients with resistant CMV or HSV infections responded to brincidofovir. Brincidofovir achieved virological response in 2 patients with confirmed UL97 mutation (ganciclovir-resistant CMV infection), but failed to control CMV when a specific UL54 mutation was present (conferring resistance to foscarnet and cidofovir), as seen with patient 3. Furthermore, brincidofovir was effective for treatment of acyclovir resistant HSV infection, as described in patient 4 which is in alignment with the high in vitro potency of brincidofovir (about 100-fold more than acyclovir) for inhibition of HSV replication. Only one patient had brincidofovir-related diarrhea without any evidence of concurrent gastrointestinal GVHD.Without the nephrotoxicity of cidofovir, brincidofovir could be an effective alternative for CMV-resistant and HSV-resistant infections. Combination therapy of brincidofovir with other antiviral agent, at a conventional or a lower dose, could be considered to potentiate efficacy and minimize side effects of the approved antiviral agents.

Drug resistant cytomegalovirus infection in children after stem cell transplantation

Drug resistant cytomegalovirus infection in children after stem cell transplantation

Advances in the diagnosis and management of AIDS-related eye disease.

AIDS-related eye disease is changing rapidly. New clinical entities have been reported, most numerous of which are the uveitis syndromes in patients with elevated CD4+ counts. Advances in management of cytomegalovirus retinitis (CMVR) include laser demarcation as an alternative to vitrectomy with silicone oil injection in macula-sparing cytomegalovirus-related retinal detachments and discontinuation of maintenance therapy in select patients with quiescent CMVR and elevated CD4+ counts. Screening guidelines have been proposed for childhood CMVR. Serial fundus photography has been recommended to improve follow-up evaluation of CMVR. A method to improve intraocular lens calculation in silicone-filled eyes has been offered. The rapidity and extent to which drug resistant cytomegalovirus infection develops has been elucidated. And the controversy of oral ganciclovir prophylaxis for cytomegalovirus disease has been argued from several angles. The following article reviews these and other advances in the understanding of AIDS-related eye disease.