Viral prophylaxis in organ transplant patients.

Viral pathogens have emerged as the most important microbial agents having deleterious effects on solid organ transplant (SOT) recipients. Antiviral chemoprophylaxis involves the administration of medications to abort transmission of, avoid reactivation of, or prevent progression to disease from, active viral infection. Cytomegalovirus (CMV) is the major microbial pathogen having a negative effect on SOT recipients. CMV causes infectious disease syndromes, augments iatrogenic immunosuppression and is commonly associated with opportunistic superinfection. CMV has also been implicated in the pathogenesis of rejection. Chemoprophylactic regimens for CMV have included oral Acyclovir / Aciclovir (Acyclovir / Aciclovir) at medium and high doses, intravenous and oral ganciclovir, and the prodrugs valAcyclovir / Aciclovir (Valacyclovir ( Valtrex )) and valganciclovir. CMV prophylactic strategies should be stratified, with the highest-risk patients receiving the most 'potent' prophylactic regimens. herpes simplex virus (HSV) reactivation in SOT recipients is more frequent, may become more invasive, takes longer to heal, and has greater potential for dissemination to visceral organs than it does in the immunocompetent host. Prophylactic regimens for CMV are also effective chemoprophylaxis against HSV; in the absence of CMV prophylaxis, Acyclovir / Aciclovir, valAcyclovir / Aciclovir or Famciclovir ( Famvir ) should be used as HSV prophylaxis in seropositive recipients. Primary varicella-zoster virus (VZV) after SOT is rare and most commonly seen in the paediatric transplant population because of VZV epidemiology. Zoster occurs in 5-15% of patients, usually after the sixth post-transplant month. Prophylactic regimens for zoster are neither practical nor cost effective after SOT because of the late onset of disease and low proportion of affected individuals. All SOT recipients should receive VZV immune globulin after contact with either varicella or zoster. Epstein-Barr virus has its most significant effect in SOT as the precipitating factor in the development of post-transplant lymphoproliferative disorders. Antiviral agents that could be effective are the same as those used for CMV, but indications for and effectiveness of prophylaxis are poorly established. Hepatitis B virus (HBV) and hepatitis C virus (HCV) are important pathogens in the SOT population as indications for transplantation. So-called 'prophylaxis' for recurrent HBV and HCV after liver transplantation is controversial, suppressive rather than preventive, and potentially lifelong. Influenza infection after SOT is acquired by person-to-person contact. During epidemic periods of influenza, transplant populations experience a relatively high frequency of infection, and influenza may affect immunosuppressed SOT recipients more adversely than immunocompetent individuals. Antiviral medications for prevention of influenza are administered as post-exposure prophylaxis to SOT recipients, in addition to yearly vaccine, in circumstances such as influenza epidemics and nosocomial outbreaks, and after exposure to a symptomatic individual during 'flu season'.

The comparative effects of Famciclovir ( Famvir ) and Valacyclovir ( Valtrex ) on herpes simplex virus type 1 infection, latency, and reactivation in mice.

Infections by herpes simplex virus (HSV) cannot yet be eliminated, but the severity of the disease can be reduced. Two newer drugs with established efficacy for such infections, Famciclovir ( Famvir ) and Valacyclovir ( Valtrex ), were tested in a mouse eye model of HSV infection. Both drugs significantly reduced mortality and titers of virus shed from the eyes of mice infected with an otherwise lethal dose of HSV type 1 (HSV-1). Similar titers of HSV-1 were found in the eyes, ganglia, and brains of treated animals. Although Valacyclovir ( Valtrex ) reduced the latent viral DNA load better in these studies than did Famciclovir ( Famvir ), rates of reactivation by explantation and UV exposure were the same. Thus, in this study, Famciclovir ( Famvir ) and Valacyclovir ( Valtrex ) were equally effective in limiting the virulence and spread of HSV-1, despite their biochemical and pharmacologic differences.

Several options for antiviral treatment trials in multiple sclerosis--but which targets should be selected?

Involvement of viruses in the pathogenesis of multiple sclerosis (MS) is a long-lived hypothesis, which is has not yet been proven nor refuted. This is partly due to difficulties in the evaluation of diagnostic findings on persistent infections by common viruses such as Herpes viruses and endogenous retroviruses. Progress in antiviral treatment of central nervous system (CNS) Herpes virus infections has stimulated controlled trials of long-term therapy with Acyclovir / Aciclovir and Valacyclovir ( Valtrex ) in MS, but conclusive results are not yet available. Other treatment possibilities might include anti-retroviral therapy, as well as attempts to counteract the effects of viruses in triggering attacks of MS following upper respiratory tract infections. Before such trials are initiated, however, further diagnostic evidence of the involvement of target viruses seems warranted.

Valacyclovir ( Valtrex ) for the prevention of cytomegalovirus infection after allogeneic stem cell transplantation: a single institution retrospective cohort analysis.

A retrospective single center study was performed to evaluate the safety and efficacy of Valacyclovir ( Valtrex ) for prevention of cytomegalovirus (CMV) infection (reactivation) after allogeneic stem cell transplantation (SCT). We compared a group of 31 patients at risk for CMV reactivation (donor, recipient or both seropositive for CMV) who received Valacyclovir ( Valtrex ) at an oral dose of 1 g three times a day for CMV prophylaxis with a matched cohort of 31 patients who did not receive the drug or any other form of CMV prophylaxis. Valacyclovir ( Valtrex ) was used as primary prophylaxis in 12 patients and as secondary prophylaxis (after a prior CMV reactivation was effectively treated with either ganciclovir or foscarnet and without CMV antigenemia at the start of Valacyclovir ( Valtrex )) in the remaining 19 patients. The two treatment groups were well matched for the donor-recipient CMV serological status and other pre-transplant characteristics. CMV reactivation was detected by blood antigenemia testing using a commercially available immunofluorescence assay for CMV lower matrix protein pp65 in circulating leukocytes. For primary prophylaxis, 3/12 patients who received Valacyclovir ( Valtrex ) reactivated CMV compared to 24/31 patients in the control group (P < 0.001). For secondary prophylaxis, 5/19 Valacyclovir ( Valtrex ) patients reactivated compared to 16/24 control patients (P < 0.05). Valacyclovir ( Valtrex ) was well tolerated except for infrequent and mild gastrointestinal side-effects. There was no difference in the incidence of CMV disease in the two groups. Prophylaxis with Valacyclovir ( Valtrex ) appears to be safe and efficacious in preventing both primary and secondary CMV reactivation in at-risk patients after allogeneic SCT. Larger prospective randomized studies will be required to confirm these observations.