valganciclovir and Polyomavirus-Infections

A series of substudies of a large international cytomegalovirus (CMV) prophylaxis trial investigated the incidence and clinical relevance of reactivation of human herpesviruses 6, 7, and 8, varicella zoster virus, Epstein-Barr virus, polyomavirus, and adenovirus, and the effect of CMV prophylaxis on clinical and subclinical non-CMV viral infections, in adult solid organ transplant (SOT) patients. Results of the substudy analyses showed that viremia caused by a number of viruses is surprisingly common posttransplantation; most of these infections likely represent reactivation of endogenous latent virus. In addition, although infection or active viral replication was common in this cohort of SOT patients, symptomatic disease due to these viruses was uncommon and the clinical sequelae of viremia were unclear or not apparent. CMV prophylaxis may have modified the natural history of some of these non-CMV viral infections.

Topics: Antiviral Agents; BK Virus; Cytomegalovirus Infections; Double-Blind Method; Epstein-Barr Virus Infections; Ganciclovir; Herpesvirus 4, Human; Herpesvirus 6, Human; Herpesvirus 7, Human; History, 16th Century; Humans; Organ Transplantation; Polyomavirus Infections; Postoperative Complications; Valganciclovir; Viremia; Virus Activation

Immunomodulatory effects attributable to cytomegalovirus (CMV) would predispose to BK polyomavirus (BKPyV) infection after kidney transplantation (KT), although available evidence is conflicting. It has been suggested that (val)ganciclovir therapy may increase the risk of BKPyV viremia and BKPyV-associated nephropathy (BKPyVAN) as a result of drug-induced T-cell impairment.. We investigated whether CMV replication and/or (val)ganciclovir exposure (either as prophylaxis or treatment) were associated with the development of BKPyV viremia or BKPyVAN in a prospective cohort of 399 KT recipients. CMV infection (any level or high-level viremia and area under the curve of DNAemia) and (val)ganciclovir exposure (any duration of therapy and cumulative days of treatment) during the first post-transplant year were explored through separate landmark survival analyses.. Cumulative incidence of BKPyV viremia and BKPyVAN after a median follow-up of 551 days was 23.1% and 2.5%, respectively. One-year rates of CMV infection and (val)ganciclovir therapy were 47.4% and 54.1%, respectively. No differences were observed in BKPyV viremia- or BKPyVAN-free survival according to previous CMV infection or (val)ganciclovir exposure in any of the landmark analyses. Adjusted Cox models confirmed this lack of association.. Our findings do not confirm the existence of a relevant impact of CMV infection or (val)ganciclovir therapy on the risk of post-transplant BKPyV events.

Topics: Antiviral Agents; BK Virus; Cytomegalovirus Infections; Ganciclovir; Humans; Kidney Transplantation; Nephritis, Interstitial; Polyomavirus Infections; Prospective Studies; Tumor Virus Infections; Valganciclovir; Viremia

Topics: BK Virus; Cytomegalovirus; Cytomegalovirus Infections; Humans; Kidney Diseases; Polyomavirus Infections; Valganciclovir; Viremia

Topics: BK Virus; Cytomegalovirus; Cytomegalovirus Infections; Humans; Polyomavirus Infections; Risk Factors; Valganciclovir; Viremia

Polyomavirus BK (BKV) is the cause of polyomavirus-associated nephropathy resulting in premature graft loss. There are limited data regarding the role of cytomegalovirus (CMV) infection and its prevention in developing BKV viremia and PVAN. In a prospective study, we analyzed 207 consecutive renal transplant recipients previously enrolled in 2 randomized trials evaluating different CMV prevention regimens with routine screening for BKV and CMV. Of these, 59 received valganciclovir and 100 valacyclovir prophylaxis; 48 patients were managed by preemptive therapy. At 3 years, the incidence of BKV viremia and PVAN was 28% and 5%, respectively. CMV DNAemia developed in 55% and CMV disease in 6%. Both BKV viremia (42% vs 23% vs 21%, P = .006) and PVAN (12% vs 2% vs 2%, P = .011) were increased in patients treated with valganciclovir prophylaxis compared to valacyclovir and preemptive therapy. Using multivariate Cox proportional hazard regression, valganciclovir prophylaxis was independent predictor of BKV viremia (hazard ratio [HR] = 2.38, P = .002) and PVAN (HR = 4.73, P = .026). In contrast, the risk of subsequent BKV viremia was lower in patients with antecedent CMV DNAemia (HR = 0.50, P = .018). These data suggest valganciclovir prophylaxis may be associated with increased risk of BKV viremia and PVAN. CMV DNAemia did not represent a risk for BKV.

Topics: Adult; BK Virus; Cytomegalovirus; Cytomegalovirus Infections; Female; Graft Survival; Humans; Kidney Failure, Chronic; Kidney Transplantation; Male; Middle Aged; Multivariate Analysis; Polyomavirus Infections; Premedication; Proportional Hazards Models; Prospective Studies; Randomized Controlled Trials as Topic; Risk Factors; Treatment Outcome; Tumor Virus Infections; Valacyclovir; Valganciclovir; Viremia

Topics: Acitretin; Antiviral Agents; Ganciclovir; HIV Infections; Humans; Keratolytic Agents; Male; Middle Aged; Polyomavirus; Polyomavirus Infections; Skin Diseases, Papulosquamous; Treatment Outcome; Valganciclovir