valacyclovir and Opportunistic-Infections

Opportunistic viral infections are a well-recognized complication of anti-tumor necrosis factor (TNF) therapy for inflammatory bowel disease (IBD). Cases of severe or atypical varicella zoster virus infection, both primary and latent reactivation, have been described in association with immunosuppression of Crohn's disease (CD) patients. However, central nervous system varicella zoster virus infections have been rarely described, and there are no previous reports of varicella zoster virus meningitis associated with anti-TNF therapy among the CD population. Here, we present the case of a 40-year-old male with severe ileocecal-CD who developed a reactivation of dermatomal herpes zoster after treatment with prednisone and adalimumab. The reactivation presented as debilitating varicella zoster virus meningitis, which was not completely resolved despite aggressive antiviral therapy with prolonged intravenous acyclovir and subsequent oral valacyclovir. This is the first reported case of opportunistic central nervous system varicella zoster infection complicating anti-TNF therapy in the CD population. This paper also reviews the literature on varicella zoster virus infections of immunosuppressed IBD patients and the importance of vaccination prior to initiation of anti-TNF therapy.

Topics: Acyclovir; Adalimumab; Adrenal Cortex Hormones; Adult; Antibodies, Monoclonal, Humanized; Antiviral Agents; Crohn Disease; Herpes Zoster; Herpesvirus 3, Human; Humans; Immunocompromised Host; Immunosuppressive Agents; Male; Meningitis, Viral; Opportunistic Infections; Prednisone; Treatment Outcome; Tumor Necrosis Factor-alpha; Valacyclovir; Valine; Virus Activation

Prevention of cytomegalovirus (CMV) infection is an important part of clinical care provided to patients after solid organ transplantation. While the optimal preventive strategy has not been defined, most centers rely on universal prophylaxis or pre-emptive therapy. This article comments on recent studies designed to identify strategies that effectively reduce the incidence of late-onset CMV disease as the main problem associated with prophylaxis, and on recent data regarding the development of CMV-specific immunity depending on the CMV-preventive regimen used. Despite an apparent trend to prefer prophylaxis in clinical practice, this approach does not seem to be based on robust evidence.

Topics: Acyclovir; Antiviral Agents; Clinical Protocols; Cytomegalovirus Infections; Ganciclovir; Humans; Immunosuppressive Agents; Opportunistic Infections; Organ Transplantation; Randomized Controlled Trials as Topic; Valacyclovir; Valganciclovir; Valine

Cytomegalovirus (CMV) infection and disease, with its extensive direct and indirect consequences, adds considerably to the cost of patient management in both solid organ and bone marrow transplantation. Antiviral prophylaxis for CMV infection can offer cost advantages over preemptive therapy and "wait-and-treat" approaches. Valacyclovir has demonstrated efficacy for CMV prophylaxis in renal, heart, and bone marrow transplantation and is cost-effective when compared with placebo in renal transplant recipients at high risk of CMV infection. In reducing CMV infection and disease, valacyclovir prophylaxis appears to be associated with reductions in indirect effects of CMV (acute graft rejection, other opportunistic infections) and, if these effects are considered, the potential exists for even greater savings to be made with valacyclovir therapy. Benefits of valacyclovir in transplantation extend beyond CMV to other herpesviruses and may be increased in some clinical situations by prolonging prophylaxis beyond 3 months.

Topics: Acyclovir; Administration, Oral; Antiviral Agents; Bone Marrow Transplantation; Cost-Benefit Analysis; Cytomegalovirus Infections; Graft Rejection; Health Care Costs; Heart Transplantation; Humans; Kidney Transplantation; Opportunistic Infections; Postoperative Complications; Prodrugs; Time Factors; Valacyclovir; Valine

A meta-analysis of 12 randomized trials (1574 patients) examined herpesvirus and related outcomes following organ transplantation over a range of acyclovir exposures (including valacyclovir). Overall, cytomegalovirus (CMV) infection (odds ratio [OR], 0.44; 95% confidence interval [CI], 0.34-0.57; P<.001), CMV disease (OR, 0.41; 95% CI, 0.31-0.54; P<.001), death (OR, 0.60; 95% CI, 0.40-0.90; P=.01), opportunistic infection (OR, 0.70; 95% CI, 0.53-0.91; P=.009), acute graft rejection (OR, 0.67; 95% CI, 0.52-0.86; P<.001), herpes simplex virus disease (OR, 0.17; 95% CI, 0.12-0.24; P<.001), and varicella-zoster virus disease (OR, 0.06; 95% CI, 0.01-0.25; P<.001) were significantly reduced. Increased acyclovir exposure influenced more end points: Maximum efficacy resulted from valacyclovir (8 g/day). Increasing acyclovir exposure to that achieved with valacyclovir extends benefits of prophylaxis to include impact on graft rejection and opportunistic infections.

Topics: Acyclovir; Antiviral Agents; Cytomegalovirus Infections; Dose-Response Relationship, Drug; Graft Rejection; Herpes Simplex; Humans; Odds Ratio; Opportunistic Infections; Organ Transplantation; Postoperative Complications; Prodrugs; Randomized Controlled Trials as Topic; Treatment Outcome; Valacyclovir; Valine

Latent cytomegalovirus (CMV) infection is present in more than half the adult population, and a viral reactivation (ie, when the virus becomes measurable in body fluids such as blood) can occur in up to one-third of these individuals during episodes of critical illness.. To determine whether antiviral therapy is safe and effective for preventing CMV reactivation in a general population of critically ill patients.. A single-center, open-label, randomized, controlled clinical trial recruited 124 CMV-seropositive patients undergoing mechanical ventilation for at least 24 hours in the intensive care unit between January 1, 2012, and January 31, 2014. The mean baseline Acute Physiology and Chronic Health Evaluation II score of all patients was 17.6.. Patients were randomized to receive anti-CMV prophylaxis with valacyclovir hydrochloride (n = 34) or low-dose valganciclovir hydrochloride (n = 46) for up to 28 days to suppress viral reactivation, or to a control group with no intervention (n = 44).. Time to first CMV reactivation in blood within the 28-day follow-up period following initiation of the study drug.. Among the 124 patients in the study (46 women and 78 men; mean [SD] age, 56.9 [16.9] years), viral reactivation in the blood occurred in 12 patients in the control group, compared with 1 patient in the valganciclovir group and 2 patients in the valacyclovir group (combined treatment groups vs control: hazard ratio, 0.14; 95% CI 0.04-0.50). Although this trial was not powered to assess clinical end points, the valacyclovir arm was halted prematurely because of higher mortality; 14 of 34 patients (41.2%) had died by 28 days, compared with 5 of 37 (13.5%) patients in the control arm at the point of the decision to halt this arm. Other safety end points showed similar outcomes between groups.. Antiviral prophylaxis with valacyclovir or low-dose valganciclovir suppresses CMV reactivation in patients with critical illness. However, given the higher mortality, a large-scale trial would be needed to determine the clinical efficacy and safety of CMV suppression.. clinicaltrials.gov Identifier: NCT01503918.

Topics: Acyclovir; Adult; Aged; Antiviral Agents; Critical Illness; Cytomegalovirus; Cytomegalovirus Infections; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Opportunistic Infections; Respiration, Artificial; Valacyclovir; Valine; Virus Activation; Virus Inactivation

The objective of this study was to evaluate the comparability of systemic aciclovir exposure at steady state in immunocompromised patients following oral valaciclovir 1000 mg tds and intravenous (iv) aciclovir 5 mg/kg tds. A two-centre, randomized, open label, two-way crossover study was undertaken. Patients aged 18-65 years who had undergone high-dose chemotherapy for cancer and were neutropenic (neutrophil count <0.5 x 109/mL) with normal renal function were recruited. The pharmacokinetic parameters of aciclovir after oral valaciclovir 1000 mg or iv aciclovir 5 mg/kg given as 1 h infusion, each administered every 8 h for seven doses, were compared. Fifteen patients were enrolled and 13 completed both treatments. The mean (s.d.) values for aciclovir after oral valaciclovir and iv aciclovir were: AUC0-8 76.3 (29.7) and 64.2 (20.0) microM x h; peak plasma concentration (Cmax) 26.6 (10.5) and 34.0 (11.9) microM; time to maximal plasma concentration (tmax) 2.01 (0.65) and 0.95 (0.19); and plasma elimination half-life (t1/2) 2.83 (0.91) and 2.44 (0.62) h, respectively. The mean absolute bioavailability of aciclovir from oral valaciclovir was 60 +/- 21%. Equivalent systemic exposure to aciclovir after oral valaciclovir 1000 mg and iv aciclovir 5 mg/kg was observed with AUC0-8 (oral/iv ratio = 1.16; 90% CI 0.98-1.39), whilst significantly reduced peak aciclovir concentrations were obtained with oral valaciclovir (ratio = 0.75; 90% CI 0.60-0.94). Oral valaciclovir offers a convenient, and possibly safer, alternative to iv aciclovir, delivering comparable systemic exposures with reduced peak levels. This may contribute to shorter hospitalization, reduced costs for healthcare providers and improved quality of life for patients.

Topics: Acyclovir; Administration, Oral; Adolescent; Adult; Aged; Antiviral Agents; Female; Herpes Simplex; Humans; Immunocompromised Host; Infusions, Intravenous; Male; Middle Aged; Neoplasms; Opportunistic Infections; Valacyclovir; Valine

Cytomegalovirus infection is a major cause of morbidity and mortality in solid-organ transplant. Low doses of valacyclovir have been administered as cytomegalovirus prophylaxis in our institution for years. To the best of our knowledge, there is no published study of a low-dose regimen for cytomegalovirus prophylaxis in heart transplant patients. Therefore, our aim was to determine the results of low doses of valacyclovir in heart transplant.. Between September 2006 and December 2014, sixty-eight patients underwent orthotopic heart transplants. All of the patients received triple immunosuppressive therapy after surgery. During the next 6 months, sulfamethoxazole/trimethoprim was administered for Pneumocystis jiroveci pneumonia, and toxoplasmosis. Additionally all patients received valacyclovir hydrochloride (1000 mg/d, oral) for cytomegalovirus prophylaxis and nystatin oral rinse for prophylaxis of fungal infections.. There was only 1 cytomegalovirus infection at follow-up. The patient had cytomegalovirus pneumonia at 17-month follow-up. In response to treatment with 1-week intravenous ganciclovir, the patient was discharged with a further 6-month oral valacyclovir therapy (1000 mg/d).. In this study, we hypothesized that daily use of low-dose valacyclovir (1000 mg/d) is not only sufficient for cytomegalovirus prophylaxis but also beneficial in terms of cost.

Topics: Acyclovir; Adolescent; Adult; Antiviral Agents; Cytomegalovirus; Cytomegalovirus Infections; Drug Administration Schedule; Drug Therapy, Combination; Female; Heart Transplantation; Humans; Immunocompromised Host; Immunosuppressive Agents; Male; Middle Aged; Opportunistic Infections; Pneumonia, Viral; Risk Factors; Time Factors; Treatment Outcome; Valacyclovir; Valine; Virus Activation; Young Adult

We report a challenging case of an atypical presentation of recrudescent herpes simplex virus infection in a patient with common variable immunodeficiency. Oral infections in immunosuppressed patients may present with unusual clinical features that can mimic non-infectious diseases. This report discusses the diagnostic steps necessary for definitive diagnosis and to guide appropriate and effective management.

Topics: Acyclovir; Antiviral Agents; Common Variable Immunodeficiency; Diagnosis, Differential; Female; Humans; Immunocompromised Host; Lichen Planus, Oral; Middle Aged; Opportunistic Infections; Stomatitis, Herpetic; Valacyclovir; Valine

Topics: Acyclovir; Aged, 80 and over; Antibodies, Monoclonal, Murine-Derived; Antiviral Agents; Blister; Hemorrhage; Herpes Zoster; Herpesvirus 3, Human; Humans; Immunologic Factors; Male; Opportunistic Infections; Purpura, Thrombocytopenic, Idiopathic; Rituximab; Valacyclovir; Valine

Biological agents such as inhibitors of tumour necrosis factor alpha (TNF-alpha ) are associated with the development of opportunistic infections. Although there are no international recommendations for the management of opportunistic infections, their prevention is a key safety issue for patients with inflammatory bowel disease (IBD). We report that chemoprophylaxis with oral valaciclovir was effective in preventing Herpes simplex virus (HSV-1) reactivation in a girl treated with infliximab for Crohn's disease.

Topics: Acyclovir; Adult; Anti-Inflammatory Agents; Antibodies, Monoclonal; Crohn Disease; Female; Herpesvirus 1, Human; Humans; Infliximab; Opportunistic Infections; Secondary Prevention; Valacyclovir; Valine; Virus Activation

Cytomegalovirus (CMV) is a major pathogen in renal transplant patients causing significant post-transplant morbidity and mortality. Prophylactic antiviral therapy, currently implemented in most kidney transplant centres, has significantly reduced the incidence of CMV infection after transplantation. Oral ganciclovir has been shown to be an effective prophylactic agent in preventing CMV disease and infection with a demonstrated superior efficacy over oral acyclovir. Valacyclovir, a prodrug of acyclovir with a higher level of bioavailability than acyclovir, has also been shown to be effective in preventing CMV disease when given as prophylactic treatment.. In a retrospective analysis of 150 renal transplant recipients in our centre, we compared the efficacy of oral ganciclovir with valacyclovir in preventing CMV infection. Seventy-seven consecutive renal transplant recipients prophylactically treated with oral ganciclovir for 12 weeks after transplant were compared with 73 consecutive recipients treated with oral valacylovir for an equal length of time.. No difference was noted in the incidence of CMV infection between the two treatment groups (5.1 vs 5.4%) after a 6 month follow-up. Likewise, the incidence of acute rejection was similar in both groups (11.6 vs 6.8%). All cases of CMV infection occurred in high-risk patients (donor positive/recipient negative).. The prophylactic use of oral valacylovir is as effective as oral ganciclovir in reducing CMV infection and disease after kidney transplantation.

Topics: Acyclovir; Administration, Oral; Adult; Cytomegalovirus Infections; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Follow-Up Studies; Ganciclovir; Graft Rejection; Graft Survival; Humans; Kidney Failure, Chronic; Kidney Transplantation; Male; Middle Aged; Opportunistic Infections; Preoperative Care; Probability; Retrospective Studies; Risk Assessment; Treatment Outcome; Valacyclovir; Valine