acyclovir and Virus-Diseases

Viral infections in the fetus or newborn often involve the central nervous system (CNS) and can lead to significant morbidity and mortality. Substantial progress has been made in identifying interventions decreasing adverse neurodevelopmental outcomes in this population. This review highlights progress in treatment of important viruses affecting the CNS in these susceptible hosts, focusing on herpes simplex virus (HSV), cytomegalovirus (CMV), human immunodeficiency virus (HIV), and enteroviruses. The observation that high-dose acyclovir improves mortality in neonatal HSV disease culminated decades of antiviral research for this disease. More recently, prolonged oral acyclovir was found to improve neurologic morbidity after neonatal HSV encephalitis. Ganciclovir, and more recently its oral prodrug valganciclovir, is effective in improving hearing and neurodevelopment after congenital CMV infection. Increasing evidence suggests early control of perinatal HIV infection has implications for neurocognitive functioning into school age. Lastly, the antiviral pleconaril has been studied for nearly two decades for treating severe enteroviral infections, with newer data supporting a role for this drug in neonates. Identifying common mechanisms for pathogenesis of viral CNS disease during this critical period of brain development is an important research goal, highlighted by the recent emergence of Zika virus as a potential cause of fetal neurodevelopmental abnormalities.

Topics: Acyclovir; Antiviral Agents; Brain; Cognition; Cognition Disorders; Encephalitis, Herpes Simplex; Enterovirus Infections; Female; Ganciclovir; HIV Infections; Humans; Infant, Newborn; Nervous System Diseases; Oxadiazoles; Oxazoles; Pregnancy; Valganciclovir; Virus Diseases

Neonatal fungal and viral infections are associated with mortality and neurologic impairment among survivors. Advances in pharmacokinetics (PK) and pharmacodynamics (PD) of antimicrobial medications have led to improved dosing guidance for neonates. This article discusses the basic PK/PD properties and dosing of the most common antifungal and antiviral medications used in neonates.

Topics: Acyclovir; Amphotericin B; Antifungal Agents; Antiviral Agents; Candidiasis, Invasive; Cytomegalovirus Infections; Deoxycholic Acid; Drug Combinations; Fluconazole; Ganciclovir; Herpes Simplex; Humans; Infant; Infant, Newborn; Mycoses; Practice Guidelines as Topic; Pregnancy Complications, Infectious; Valganciclovir; Virus Diseases

Herpes viruses (herpes simplex, varicella zoster, cytomegalovirus) are the main cause of a wide variety of human infections. Although the development of successful antiviral agents against infections caused by herpes viruses had been slow until the last decade, the production of delivery systems for acyclovir are a promising alternative. The present review summarizes the principal advances made in developing carriers for the delivery of acyclovir by different routes of administration.

Topics: Acyclovir; Animals; Antiviral Agents; Drug Delivery Systems; Humans; Prodrugs; Virus Diseases

This review article, while autobiographical to some extent, describes the discovery of ten (classes of) antiviral compounds that have made (or just did not make) it to the market for the therapy of viral infections, but each in its own way influenced the landscape of our dealing with virus infections: (i) valaciclovir, (ii) BVDU, (iii) DHPA, (iv) cidofovir, (v) adefovir, (vi) tenofovir, (vii) stavudine, (viii) HEPT, (ix) TIBO, and (x) AMD3100. Successful drug development, as is certainly true for antiviral drugs and exemplified for the acyclic nucleoside phosphonates cidofovir, adefovir and tenofovir, requires patience and perseverance, and a close continuous and dedicated interaction between Chemistry, Biology/Medicine and Industry.

Topics: Acyclovir; Adenine; Antiviral Agents; Benzodiazepines; Benzylamines; Cidofovir; Cyclams; Cytosine; Heterocyclic Compounds; Humans; Imidazoles; Nucleosides; Organophosphonates; Tenofovir; Valacyclovir; Valine; Virus Diseases

During the last three decades, a better understanding of viral replication and disease states caused by viral infections have led to the development of newer antiviral agents with enhanced activity and better tolerability. This review focuses on newer systemic and topical antiviral agents that are used in treatment of herpes viruses including herpes simplex type-1 (HSV-1) and type-2 (HSV-2), varicella-zoster virus (VZV) and cytomegalovirus CMV) as well as the human papilloma virus (HPV). Included in this article are the agents famciclovir, penciclovir, valganciclovir, imiquimod, docosanole and brivudin.

Topics: 2-Aminopurine; Acyclovir; Aminoquinolines; Antiviral Agents; Bromodeoxyuridine; Famciclovir; Fatty Alcohols; Ganciclovir; Guanine; Humans; Imiquimod; Valganciclovir; Virus Diseases

The amount of antiviral drugs have increased recently. Many viruses treated as a mild pathogens has turned out to cause different complications and severe diseaseses in elderly people and immunocomprised patients. The authors have made an attempt of presenting on the basis of scientific reports the principles of antiviral prophylaxis and treatment. The first part is focused on infections caused by DNA viruses.

Topics: Acyclovir; Aged; Antiviral Agents; Chickenpox; DNA Viruses; Female; Herpes Zoster; Humans; Male; Vaccination; Virus Diseases

Effective treatment requires administration of optimal drug dose. In paediatric patients this may be difficult to achieve due to lack of pharmacokinetic studies, administration of small doses, changes in body composition, continuous growth, and development and maturation of organs and systems. This article reviews the factors and misconceptions associated with determining optimal drug dose and route of administration in different paediatric populations. The pharmacokinetics, appropriate doses and preferred routes of administration for aciclovir, ganciclovir, famciclovir, foscarnet and cidofovir, for treating herpesvirus infections in the paediatric population, are discussed.

Topics: 2-Aminopurine; Acyclovir; Antiviral Agents; Child; Child, Hospitalized; Cidofovir; Cytosine; Famciclovir; Foscarnet; Ganciclovir; Humans; Organophosphonates; Organophosphorus Compounds; Virus Diseases

Valaciclovir is an aciclovir pro-drug considerably improving its oral availability. Its antiviral activity in vivo is related to that of aciclovir, the principle target of which is the herpes virus. Following digestive absorption, valaciclovir is rapidly transformed into aciclovir. The mean absolute bioavailability of aciclovir is of 54.2% after a single oral dose of 1,000 mg of valaciclovir, i.e., a bioavailability 3 to 5-fold greater than after oral ingestion of aciclovir. The plasma pharmacokinetic profile of valaciclovir and aciclovir observed in volunteers infected by HIV is superimposable on that of healthy subjects. In elderly patients, exposure to aciclovir is enhanced, probably because of the alteration in glomerular filtration. In patients exhibiting agranulocytosis following poly-chemotherapy, the pharmacokinetic parameters are superimposable on those observed in healthy patients. In patients with hepatic failure, there appears no need to adapt the dose, since exposure to aciclovir does not appear altered. However, the dose of valaciclovir must be adapted to renal function. During the first-episode of herpes genitalis, valaciclovir, at the dose of 500 or 1,000 mg twice daily, is as effective as 200 mg of aciclovir five times per day. In recurrent herpes genitalis, 500 mg twice daily of valaciclovir is as effective as 1,000 mg twice daily or 200 mg five times a day of aciclovir. Valaciclovir prevents recurrence herpes genitalis with a dose-dependent effect, and doses of 500 and 1,000 mg/day are as effective as 400 mg twice daily of aciclovir. There are few studies on the efficacy of valaciclovir in the treatment of oro-facial herpes. In the treatment of herpes zoster in patients aged over 50, the principle benefit provided by valaciclovir at the dose of 1,000 mg twice daily, is the decrease in the percentage of patients presenting post-zoster pain and its duration. High doses of valaciclovir (8 capsules/day) provide efficient prevention of infections related to the cyto-megalo-virus (CMV) in immunodepressed patients due to HIV infection or following renal transplantation. Tolerance to valaciclovir, like its active metabolite aciclovir, is generally good. Central neurological toxicity is frequently observed with high doses, but regresses on withdrawal. The official indications in France are the curative and preventive treatment of herpes genitalis infections, the prevention of post-zoster pain and the ocular complications of ophthalmologic herpes

Topics: Acyclovir; Humans; Prodrugs; Valacyclovir; Valine; Virus Diseases

Antiviral prophylaxis in pediatric oncology and pediatric bone marrow transplantation (BMT)/stem cell transplantation (SCT) focuses herpes viruses: herpes simplex virus (HSV), varicella zoster virus (VZV) and cytomegalovirus (CMV) since these viruses cause significant morbidity and mortality due to primary infection or to reactivation in long term latency. The majority of studies on antiviral prophylaxis, especially those on CMV-prophylaxis, have been conducted in adult patients. Recommendations for antiviral prophylaxis have been published recently by the German "Deutsche Gesellschaft für pädiatrische Infektiologie" and by the following American institutions and societies "Centers for Disease Control and Prevention", "Infectious Diseases Society of America", "American Society of Blood and Marrow Transplantation" who published the "Guidelines for Preventing Opportunistic Infections Among Hematopoietic Stem Cell Transplant Recipients". Concerning HSV- and VZV-prophylaxis there are almost no differences between recommendations of the german society and the american institutions, however recommendations for preventing CMV-disease and CMV-recurrence do differ considerably. Controversial aspects of antiviral prophylaxis, e.g. VZV vaccination or CMV prevention, should be studied in oncology and infectious diseases working groups to define consensus in the near future.

Topics: Acyclovir; Adult; Age Factors; Antiviral Agents; Bone Marrow Transplantation; Chickenpox; Child; Cytomegalovirus Infections; Ganciclovir; Hematopoietic Stem Cell Transplantation; Herpes Simplex; Humans; Immunization, Passive; Neoplasms; Practice Guidelines as Topic; Randomized Controlled Trials as Topic; Recurrence; Time Factors; Viral Vaccines; Virus Diseases

Topics: 2-Aminopurine; Acyclovir; Antiviral Agents; Famciclovir; Family Practice; Female; Herpesviridae Infections; Humans; Infant, Newborn; Infectious Disease Transmission, Vertical; Male; Pregnancy; Pregnancy Complications, Infectious; Randomized Controlled Trials as Topic; Sexually Transmitted Diseases, Viral; Virus Diseases

Treatment options for peripheral facial palsy (PFP) are an often discussed problem in neurologic practice. Following a short description of the complex anatomy of the seventh cranial nerve we therefore review possible etiologies in the context of leading clinical signs, with idiopathic PFP or Bell's palsy (BP) being most frequent. A rather typical clinical course of BP allows to focus differential diagnostic workup predominantly on the rapid identification of treatable infections such as with Herpes zoster or Borrelia burgdorferi. Neuroimaging studies are needed only in case of trauma, with slowly developing PFP or in the presence of associated signs and symptoms. As BP is characterized by an overall high rate of spontaneous recovery, major emphasis has to be put on avoiding complications by protecting the eye. Meta-analysis of four randomized controlled studies suggests a marginal benefit of steroids concerning eventual achievement of complete recovery. Beneficial effects of a combination of acyclovir and prednisone have also been claimed. While such therapies may be considered in patients with a presumptive bad prognosis, more general recommendations on medical treatment of BP will have to await further trials.

Topics: Acyclovir; Adrenal Cortex Hormones; Anti-Inflammatory Agents; Antiviral Agents; Clinical Trials as Topic; Diabetic Neuropathies; Diagnosis, Differential; Diagnostic Imaging; Eye Injuries; Facial Nerve; Facial Nerve Injuries; Facial Paralysis; Herpes Simplex; Humans; Neoplasms; Pons; Postoperative Complications; Prednisone; Prognosis; Virus Diseases

Several new agents for treating viral infections have been developed in recent years. All available agents are virustatic, inhibiting specific steps in the process of viral replication. No agent is active against nonreplicating or latent viruses. Acyclovir is useful in the treatment of genital herpes, herpes simplex encephalitis, mucocutaneous herpetic infection, varicella infection in the immunosuppressed host, and herpes zoster infection in the normal and the immunosuppressed host. It can also be used for prevention of herpesvirus infection in immunocompromised patients. Ganciclovir is indicated for the treatment of cytomegalovirus retinitis in patients with the acquired immunodeficiency syndrome and is effective in the treatment and prevention of cytomegalovirus infection in other immunocompromised patients. Famciclovir and valacyclovir are effective in the management of herpes simplex and varicella-zoster infection. Amantadine and rimantadine are useful therapeutically and prophylactically in the management of influenza A virus infection. Chronic hepatitis B infection can respond to lamivudine therapy, and the optimal treatment of hepatitis C is the combination of interferon alfa and ribavirin. Despite pronounced toxic effects, foscarnet and cidofovir are effective antiviral agents in specific settings.

Topics: 2-Aminopurine; Acetamides; Acyclovir; Amantadine; Antiviral Agents; Cidofovir; Cytosine; Drug Resistance, Microbial; Drugs, Investigational; Enzyme Inhibitors; Famciclovir; Foscarnet; Ganciclovir; Guanidines; Guanine; Humans; Interferons; Lamivudine; Neuraminidase; Organophosphonates; Organophosphorus Compounds; Oseltamivir; Pyrans; Ribavirin; Sialic Acids; Valacyclovir; Valine; Virus Diseases; Zanamivir

Several antiviral agents are available to treat viral illnesses in healthy children. In some children, treatment with acyclovir is an alternative to vaccination for the treatment and prevention of chickenpox. Acyclovir also can be useful in the treatment or prevention of herpes simplex infections in neonates. Ribavirin, once recommended as routine therapy for high-risk infants with respiratory syncytial virus disease, is now reserved for use in selected children. Amantadine and rimantidine are effective against influenza type A and can be used to protect children from influenza, as well as to lessen the duration and severity of illness in those who are already ill.

Topics: Acyclovir; Amantadine; Antiviral Agents; Chickenpox; Child; Child, Preschool; Drug Administration Schedule; Herpes Simplex; Humans; Respiratory Syncytial Virus Infections; Ribavirin; Rimantadine; Virus Diseases

Topics: Acyclovir; Antiviral Agents; Humans; Japan; Magnetic Resonance Imaging; Nervous System Diseases; Serologic Tests; Vidarabine; Virus Diseases

Viral lesions of the mouth in patients with HIV infection are common and these diseases any be a marker for HIV and disease progression. We review the spectrum of oral viral manifestations and discuss treatment modalities. The most common Epstein-Barr virus (EBV)-induced disorder in HIV-infected patients is oral hairy leukoplakia. EBV-related oral B-cell and T-cell lymphoma in AIDS patients has been described repeatedly. Herpes virus type 1 and rarely type 2 may lead to painful and resistant oral ulcers, and systemic treatment with acyclovir, valaciclovir or famciclovir is indicated. In acyclovir-resistant cases foscarnet is the treatment of choice. In recent years it has been documented that Kaposi's sarcoma, which often affects oral mucosa, is probably induced by herpesvirus type 8. Cytomegalovirus was found in 53% of cases with herpesviridae-induced mucosal ulcers as the only ulcerogenic viral agent in AIDS patients. In severe cytomegalovirus infection treatment with ganciclovir is helpful. Viral warts induced by different HPV may occur in the mouth. Several physical treatment modalities are possible in the oral mucosa. In AIDS patients mollusca contagiosa may occur as large and atypical lesions in the face and lips and rarely in the oral cavity. Cryotherapy is a bloodless treatment in such patients.

Topics: 2-Aminopurine; Acyclovir; AIDS-Related Opportunistic Infections; Anti-HIV Agents; Cytomegalovirus Infections; Disease Progression; Famciclovir; Foscarnet; Ganciclovir; Herpesviridae Infections; Herpesvirus 1, Human; Herpesvirus 2, Human; Herpesvirus 4, Human; Herpesvirus 8, Human; Humans; Leukoplakia, Hairy; Lymphoma, B-Cell; Lymphoma, T-Cell; Molluscum Contagiosum; Mouth Diseases; Mouth Neoplasms; Oral Ulcer; Prodrugs; Sarcoma, Kaposi; Stomatitis, Herpetic; Tumor Virus Infections; Valacyclovir; Valine; Virus Diseases; Warts

Thanks to a simplification of surgical techniques, single or double lung transplants have expanded significantly in latter years. Infection remains an important cause for morbidity and mortality, more so in early rather than late stages. Bacterial infections cause approximately fifty per cent of all infections. They can be prevented in part by prophylaxis. Infections to CMV have become less frequent thanks to adequate prophylaxis with ganciclovir. Herpetic infections are prevented by acyclovir or ganciclovir. A better control of immunosuppression seems to be associated with fewer lymphoproliferative disorders secondary to the Epstein-Barr virus. Respiratory viruses remain a serious threat for these patients, although infections due to respiratory syncitial virus may be attenuated by ribavirine. Fungal infections are dangerous but prophylactic prescription of azole derivatives have reduced the incidence and severity. Prophylaxis of infections to Pneumocystis carinii is essential, the use of sulfamethoxazole trimethoprim is efficacious against this as well as nocardiosis. Infections to Mycobacterium tuberculosis are often atypical and should be looked for and anticipated whenever possible.

Topics: Acyclovir; Antibiotic Prophylaxis; Antifungal Agents; Antiviral Agents; Bacterial Infections; Chemoprevention; Cytomegalovirus Infections; Ganciclovir; Graft Survival; Heart-Lung Transplantation; Herpesviridae Infections; Herpesvirus 4, Human; Humans; Immunosuppression Therapy; Lung Transplantation; Lymphoproliferative Disorders; Mycobacterium Infections, Nontuberculous; Nocardia Infections; Pneumonia, Pneumocystis; Respiratory Syncytial Virus Infections; Ribavirin; Survival Rate; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis, Pulmonary; Tumor Virus Infections; Virus Diseases

Topics: Acyclovir; Ampicillin; Anti-Bacterial Agents; Antiviral Agents; Bacterial Infections; Cefotaxime; Cells, Cultured; Cephalosporins; Cytomegalovirus Infections; Diagnosis, Differential; Enzyme-Linked Immunosorbent Assay; Erythromycin; Female; Fetal Diseases; Herpes Genitalis; Humans; Infant, Newborn; Infant, Newborn, Diseases; Penicillins; Pregnancy; Pregnancy Complications, Infectious; Prenatal Diagnosis; Ultrasonography, Prenatal; Virus Diseases

Aciclovir (acyclovir) is a nucleoside analogue with antiviral activity in vitro against the herpes simplex viruses (HSV), varicella zoster virus (VZV), Epstein-Barr virus (EBV), cytomegalovirus (CMV) and human herpesvirus 6 (HHV-6). Topical, oral or intravenous aciclovir is well established in the treatment of ophthalmic, mucocutaneous and other HSV infections, with intravenous aciclovir the accepted treatment of choice in herpes simplex encephalitis. The efficacy of aciclovir is increased with early (preferably during the prodromal period) initiation of treatment but, despite significant clinical benefit, viral latency is not eradicated, and pretreatment frequencies of recurrence usually continue after episodic acute treatment is completed. Intravenous administration has also shown benefit in the treatment of severe complications of HSV infection in pregnancy, and neonatal HSV infections. Recurrence of HSV has been completely prevented or significantly reduced during suppressive therapy with oral aciclovir in immunocompetent patients. Use of oral aciclovir is effective but controversial in the treatment of otherwise healthy individuals with varicella (chickenpox), and in some countries it has been recommended for use only in cases which may be potentially severe. The development of rash and pain associated with herpes zoster (shingles) is attenuated with oral or intravenous aciclovir therapy, ocular involvement is prevented, and post-herpetic neuralgia appears to be decreased. Similarly, in a few patients with zoster ophthalmicus, oral aciclovir has reduced the frequency and severity of long term ocular complications and post-herpetic neuralgia, and herpes zoster oticus is improved with intravenous aciclovir. Oral aciclovir has prevented recurrence of HSV genital or orofacial infections during suppressive therapy in > 70% of immunocompetent patients in most clinical trials. Suppression of latent HSV, VZV and CMV infections has been achieved in many immunocompromised patients receiving the oral or intravenous formulations. Aciclovir also appears to offer partial protection from invasive CMV disease in CMV-seropositive bone marrow transplant recipients. The few comparative trials published have shown aciclovir to be at least as effective as other investigated antivirals in the treatment of HSV infections in immunocompetent patients, and more effective than inosine pranobex in the prophylaxis of genital herpes. Similarly, in isolated clinical trials, oral a

Topics: Acyclovir; Animals; Antiviral Agents; Humans; Immunologic Deficiency Syndromes; Virus Diseases

An increasing number of antiviral agents are presently in various stages of development and testing, and an increasing number have recently been licensed for use in humans. These drugs have been used extensively to treat viral infections in immunocompromised individuals, and these studies indicate that for many antiviral agents the response to therapy is highly dependent on the integrity of the underlying host immune response. In particular, the response to zidovudine, acyclovir and ganciclovir in persons with HIV-1 infection is highly dependent upon CD4 number, which can be considered a surrogate marker for the state of host immune function in these subjects. Responses to interferons likewise can be shown to depend on the host immune response, with responses due to both direct antiviral effects of this agent as well as immunomodulatory effects mediated through interferon-induced upregulation of HLA molecule expression. The interdependence of host immunity with antiviral efficacy is underscored by the increased antiviral drug resistance in persons with advanced degrees of chronic immunosuppression, related to the higher level of viral replication and viraemia which occurs in the absence of an effective host immune response. Further definition of the precise mechanisms of these interactions should facilitate the rational design of antiviral agents and immunomodulatory therapies to improve treatment of viral infections.

Topics: Acyclovir; AIDS-Related Opportunistic Infections; Antiviral Agents; Cytomegalovirus Infections; Drug Resistance, Microbial; Ganciclovir; Herpesviridae Infections; HIV Infections; HIV-1; Humans; Immunity, Cellular; Interferons; Major Histocompatibility Complex; Virus Diseases; Zidovudine

Virus infections account for considerable morbidity in bone marrow transplant (BMT) recipients. In all ages, members of the herpes virus group are the predominant pathogens. Of these, cytomegalovirus is pre-eminent in being the most frequent cause of death due to infection associated with the transplant procedure. Considerable effort is being invested in the development of preventative and therapeutic strategies to control this virus. Other potentially life-threatening virus infections may be acquired on the transplant unit as a result of cross-infection and can be caused by enteroviruses, rotaviruses and adenoviruses. Prevention of these infections is best achieved by implementation of strict infection-control measures.

Topics: Acyclovir; Adult; Bone Marrow Transplantation; Child; Cytomegalovirus Infections; Ganciclovir; Graft vs Host Disease; Herpes Simplex; Humans; Neutropenia; Respiratory Syncytial Viruses; Respiratory Tract Infections; Respirovirus Infections; Tissue Donors; Virus Diseases

The introduction of new protocols of immune suppression and especially the use of cyclosporine have led to a marked reduction of infective pathology in children receiving transplants. Nevertheless, infections still represent a major factor of morbidity and mortality in these patients. The above study lists the main viral infections, according to apparatus involved, that may arise, also with reference to the time elapsed since transplantation. The most up-to-date diagnostic possibilities for each infection are reviewed together with some indications on therapy which may subsequently be examined in greater detail.

Topics: Acyclovir; Age Factors; Child; Child, Preschool; Gastrointestinal Diseases; Heart Transplantation; Humans; Immunoglobulins; Immunosuppressive Agents; Infant; Infant, Newborn; Kidney Transplantation; Lymphoproliferative Disorders; Pneumonia, Viral; Skin Diseases, Infectious; Urinary Tract Infections; Virus Diseases

Topics: Acyclovir; Antiviral Agents; Ganciclovir; Humans; Immunocompromised Host; Interferon-alpha; Virus Diseases; Zidovudine

The epidemiology of infections associated with orthotopic liver transplantation is summarized herein, and approaches to prophylaxis are outlined. Infection is a major complication following orthotopic liver transplantation, and more than half of transplant recipients develop at least one infection. The risk of infection is highest in the first month after transplantation, and the most common pathogens are bacteria and cytomegalovirus (CMV). Bacterial infections usually occur in the first month, arise in the abdomen, and are caused by aerobes. The peak incidence of CMV infection is late in the first month and early in the second month after transplantation. CMV syndromes include fever and neutropenia, hepatitis, pneumonitis, gut ulceration, and disseminated infection. Other significant problems are Candida intraabdominal infection, Herpes simplex mucocutaneous infection or hepatitis, adenovirus hepatitis, and Pneumocystis carinii pneumonia. Prophylaxis of infection in liver transplant recipients has not been well-studied. Several different regimens of parenteral, oral absorbable, and/or oral non-absorbable antibiotics active against bacteria and yeast have been used at various centers, but no randomized controlled trials have been conducted. Selective bowel decontamination appears to be a promising approach to the prevention of bacterial and Candida infections, while oral acyclovir may be a relatively convenient and effective agent for CMV prophylaxis.

Topics: Acyclovir; Anti-Bacterial Agents; Bacterial Infections; Cytomegalovirus Infections; Humans; Infections; Liver Transplantation; Mycoses; Parasitic Diseases; Pneumonia, Pneumocystis; Postoperative Complications; Premedication; Risk Factors; Time Factors; Virus Diseases

Topics: Acyclovir; Herpes Labialis; Herpes Zoster; Herpesviridae Infections; HIV Infections; Humans; Mouth Diseases; Stomatitis, Herpetic; Virus Diseases

Topics: Acyclovir; Adult; Aged; Aged, 80 and over; Female; Herpes Zoster; Humans; Influenza, Human; Japan; Male; Pneumonia, Viral; Sexually Transmitted Diseases; Virus Diseases

Though the reported experience with zidovudine in human pregnancies is very limited, it would seem unreasonable at this time to withhold zidovudine therapy for fetal considerations in the treatment of pregnant women with AIDS and ARC. Whether the treatment of HIV-positive women with zidovudine at any time during pregnancy reduces the risk of perinatal transmission is unknown. Therefore, the use of zidovudine for that indication should await the results of controlled trials. At present, if zidovudine therapy is required during pregnancy, the standard dosage of 200 mg every 4 hours should be used. The woman and her fetus should be monitored carefully for signs of toxicity.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Female; Humans; Pregnancy; Pregnancy Complications, Infectious; Virus Diseases; Zidovudine

Pediatricians are made familiar with antiviral drugs and are provided with specific recommendations for treatment of viral diseases. The antiviral drugs in clinical use today are discussed in terms of their doses, routes of administration, mechanisms of action, established and potential efficacies, and toxicities. These drugs include acyclovir, amantadine, trisodium phosphonoformate, ganciclovir, ribavirin, rimantadine, vidarabine, and zidovudine. Biologic response modifiers, such as interferons, are mentioned briefly in their historical context. Future trends in antiviral therapy are anticipated with mention of the most promising candidate compounds currently in preclinical trials.

Topics: Acyclovir; Antiviral Agents; Child; Herpesviridae Infections; HIV Infections; Humans; Pediatrics; Respiratory Tract Infections; Virus Diseases

Topics: Acyclovir; Antiviral Agents; Humans; Ribavirin; Vidarabine; Virus Diseases; Zidovudine

Acyclovir (aciclovir) is a nucleoside antiviral drug with antiviral activity in vitro against members of the herpes group of DNA viruses. As an established treatment of herpes simplex infection, intravenous, oral and to a lesser extent topical formulations of acyclovir provide significant therapeutic benefit in genital herpes simplex and recurrent orofacial herpes simplex. The effect of acyclovir therapy is maximised by early initiation of treatment, especially in non-primary infection which tends to have a less protracted course than the primary episode. Long term prophylactic oral acyclovir, in patients with frequent episodes of genital herpes simplex, totally suppresses recurrences in the majority of subjects; as with other infections responding to acyclovir, viral latency is not eradicated and pretreatment frequencies of recurrence return after discontinuation of treatment. Caution should accompany the prophylactic use of acyclovir in the general population, due to the theoretical risk of the emergence of viral strains resistant to acyclovir and other agents whose mechanism of action is dependent on viral thymidine kinase. Intravenous acyclovir is the treatment of choice in biopsy-proven herpes simplex encephalitis in adults, and has also been successful in the treatment of disseminated herpes simplex in pregnancy and herpes neonatorium. Intravenous and oral acyclovir protect against dissemination and progression of varicella zoster virus infection, but do not protect against post-herpetic neuralgia. In immunocompromised patients, intravenous, oral and topical acyclovir shorten the clinical course of herpes simplex infections while prophylaxis with oral or intravenous dosage forms suppresses reactivation of infection during the period of drug administration. Ophthalmic application of 3% acyclovir ointment rapidly heals herpetic dendritic corneal ulcers and superficial herpetic keratitis. Thus, despite an inability to eradicate latent virus, acyclovir administered in therapeutic or prophylactic fashion is now the standard antiviral therapy in several manifestations of herpes simplex virus infection, and indeed represents a major advance in this regard. With the exception of varicella zoster virus infections, early optimism concerning the use of the drug in diseases due to other herpes viruses has generally not been supported in clinical investigations.

Topics: Acyclovir; Animals; Humans; Virus Diseases

Potent effective antiviral drugs recently have been licensed for several viral diseases, ushering in a new era in the treatment of viral diseases. Several unique features in the process of a viral infection have been identified as target points for inhibition. The unique steps and the interfering compounds are the subject of this review.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Amantadine; Antiviral Agents; Ganciclovir; Humans; Ribavirin; Vidarabine; Virus Diseases

We have described positive clinical effects of seven different anti-viral drugs in the treatment of viral respiratory diseases; three of these agents are approved for clinical use--amantadine, acyclovir, and vidarabine. Of the remaining four, the most consistent and broadest range of effect was observed with ribavirin while rimantadine was similar to amantadine in its effect. Interferon and enviroxime, under the conditions in which they were tested, showed a range of effect from moderate to no effect. A feature of the use of ribavirin was its administration by inhalation over several hour periods as a small-particle aerosol. This allowed a total dosage not much less than might have been given by other routes, but with the advantage that it was evenly deposited over the surface of the infected respiratory tract beginning within seconds of the start of treatment and reached higher concentration in nasal secretions than in serum. It may be that aerosol administration can be used with other drugs, as suggested by preliminary results with amantadine. We regard the results presented in this chapter as very encouraging, but just a beginning. Effective therapy will set in motion a reexamination of many problems of viral respiratory tract infection, including how to develop more rapid and more precise viral diagnosis, the need for further characterization of both short- and long-term consequences of infection in the untreated host and their modification by treatment. The structure for rapid progress in treatment of viral diseases is in place, and with it should come a resolution of many long-standing problems in this area of medicine.

Topics: Acyclovir; Adult; Amantadine; Animals; Antiviral Agents; Benzimidazoles; Child; Clinical Trials as Topic; Female; Humans; Influenza, Human; Interferons; Oximes; Pneumonia, Viral; Respiratory Tract Infections; Ribavirin; Rimantadine; Sulfonamides; Vidarabine; Virus Diseases

The above discussion is not intended to be exhaustive but rather to discuss several compounds which are particularly promising at this time. There is no question that great strides have been made in the development of antiviral compounds over the past couple of decades. Many questions remain unanswered such as long-term effects on the host, possible emergence of resistant viruses, optimal routes of administration, and the proper regimens for particular viruses and diseases. In addition, current studies are evaluating combinations of antiviral agents as well as combination therapy involving interferon or antibody or immunity stimulants along with an antiviral agent. Surprising progress has been made to date resulting not only in new therapeutic modalities but promising a new era of progress.

Topics: Acyclovir; Amantadine; Antiviral Agents; DNA Viruses; Humans; Infant; Infant, Newborn; Ribavirin; RNA Viruses; Vidarabine; Virus Diseases

Topics: Acyclovir; Antiviral Agents; Chemical Phenomena; Chemistry; DNA, Viral; Ganciclovir; Herpesviridae Infections; Humans; Interferons; Phosphorylation; Picornaviridae Infections; Retroviridae Infections; Ribavirin; S-Adenosylhomocysteine; Suramin; Virus Diseases; Virus Replication

Topics: Acyclovir; Amantadine; Antiviral Agents; Bone Marrow Transplantation; Chemical Phenomena; Chemistry; Clinical Trials as Topic; DNA, Viral; Herpesviridae; Herpesviridae Infections; Humans; Idoxuridine; Influenza A virus; Influenza, Human; Keratitis, Dendritic; RNA, Viral; S-Adenosylhomocysteine; Thymidine Kinase; Trifluridine; Vidarabine; Viral Proteins; Virus Diseases

Acyclovir [9-(2-hydroxyethoxymethyl)guanine] is a newly licensed acyclic nucleoside analog that is active in vitro and in vivo against herpes simplex virus (HSV) and varicella zoster virus (VZV). This agent is available in the United States in topical and intravenous forms, and the oral preparation is currently being evaluated in clinical trials. The precise therapeutic role for acyclovir in patients with herpesvirus infections is still evolving. This article reviews the current status of this exciting new antiviral agent.

Topics: Acyclovir; Aged; Chickenpox; Cytomegalovirus Infections; Female; Herpes Genitalis; Herpes Simplex; Herpes Zoster; Humans; Infant, Newborn; Infectious Mononucleosis; Injections, Intravenous; Keratitis, Dendritic; Male; Pregnancy; Risk; Virus Diseases

Topics: Acyclovir; Adult; Animals; Antiviral Agents; Herpesviridae Infections; Humans; Idoxuridine; Infant, Newborn; Recurrence; Trifluridine; Vidarabine; Virus Diseases

With the introduction of new diagnostic techniques and the expanding choices of antiviral agents, clinical virology is rapidly becoming an important field in infectious diseases. While effective therapy for several respiratory viruses, cytomegalovirus, hepatitis B virus, and Epstein-Barr virus is not currently available, herpes simplex, varicella zoster, and influenza A associated diseases can be adequately treated in many cases at the present time. New agents such as interferon, other nucleoside analogues, and immunomodulators are being investigated for their role in the treatment of viral illnesses, and many such illnesses with high morbidity and mortality may soon have effective therapy.

Topics: Acyclovir; Amantadine; Antiviral Agents; Humans; Idoxuridine; Interferons; Serologic Tests; Time Factors; Trifluridine; Vidarabine; Virology; Virus Diseases

Topics: Acyclovir; Amantadine; Animals; Antibodies, Viral; Antiviral Agents; Chemical Phenomena; Chemistry; Foscarnet; Idoxuridine; Immunity, Cellular; Immunity, Innate; Immunotherapy; Interferons; Phosphonoacetic Acid; Vidarabine; Virus Diseases; Virus Replication

Acyclovir (acycloguanosine) is a new antiviral compound with activity against certain herpes viruses. Acyclovir is phosphorylated preferentially in virus-infected cells into its active form, acyclovir triphosphate, an inhibitor of viral-induced DNA polymerase. Acyclovir, which possesses an acyclic carbohydrate moiety, also causes premature DNA chain termination. Acyclovir has shown clinical activity against herpes simplex virus (HSV) types 1 and 2 and varicella zoster virus (VZV), but its usefulness in cytomegalovirus, Epstein-Barr virus, and chronic hepatitis B infections requires further study. In randomized clinical trials of infections caused by HSV and VZV, intravenous acyclovir has been shown to shorten the duration of viral shedding and lesion pain and hasten the resolution of skin lesions, with minimal toxicity.

Topics: Acyclovir; Clinical Trials as Topic; Cytomegalovirus Infections; Drug Resistance, Microbial; Herpes Simplex; Herpes Zoster; Humans; Injections, Intravenous; Kinetics; Virus Diseases

Topics: Acyclovir; Adult; Antiviral Agents; Burkitt Lymphoma; Chickenpox; Child; Cytomegalovirus Infections; Disease Susceptibility; Enterovirus Infections; Herpes Simplex; Herpes Zoster; Humans; Immunologic Deficiency Syndromes; Immunosuppression Therapy; Infectious Mononucleosis; Orthomyxoviridae Infections; Respirovirus Infections; Vidarabine; Virus Diseases

Only a few agents with antiviral activity are available for routine clinical use. Amantadine hydrochloride is effective in the prophylaxis of influenza A. In addition, accumulated evidence shows that amantadine has some therapeutic effect when used early in the course of an influenza A infection. Idoxuridine and adenine arabinoside have found application as topical agents in the treatment of herpes simplex keratitis. Adenine arabinoside has also been approved for the treatment of disseminated infections due to herpes zoster and herpes simplex. Acyclovir sodium has been approved as a topical agent in the treatment of limited mucocutaneous herpes simplex viral infections in immunosuppressed patients and of initial episodes of genital herpes simplex infections in patients with normal immunity. Ribavirin, an experimental agent with a wide spectrum of activity in vitro, has not fulfilled expectations in clinical trials. Because of the eradication of smallpox, methisazone has become obsolete as a prophylactic agent in smallpox.

Topics: Acyclovir; Amantadine; Animals; Antiviral Agents; Herpes Simplex; Herpes Zoster; Humans; Idoxuridine; Influenza A virus; Keratitis, Dendritic; Methisazone; Ribavirin; Smallpox; Vidarabine; Virus Diseases

Topics: Acyclovir; Administration, Oral; Administration, Topical; Chemical Phenomena; Chemistry; Drug Resistance, Microbial; Eye Diseases; Humans; Infusions, Parenteral; Kinetics; Virus Diseases

Topics: Acyclovir; Antiviral Agents; Genes, Viral; Humans; Keratitis, Dendritic; Research; USSR; Virus Diseases; Virus Replication

Topics: Acyclovir; Adenosine Monophosphate; Adenosine Triphosphatases; Antiviral Agents; Cytidine Deaminase; DNA-Directed DNA Polymerase; Humans; Nucleic Acids; Nucleoside Deaminases; Phosphorylation; Pyrophosphatases; Ribavirin; Simplexvirus; Thymidine Kinase; Virus Diseases; Virus Replication; Viruses

Topics: Acyclovir; Amantadine; Antiviral Agents; Chemical Phenomena; Chemistry; Guanine; Humans; Idoxuridine; Interferons; Methisazone; Vidarabine; Virus Diseases; Viruses

Topics: Acyclovir; Amantadine; Antiviral Agents; Herpesviridae Infections; Humans; Idoxuridine; Influenza, Human; Trifluridine; Vidarabine; Virus Diseases

As indicated in Table 1, two approaches have been taken to the development of antiviral chemotherapeutic agents. Both have met with some success although the availability of effective chemotherapeutic agents for the treatment of virus infections is very limited. This situation should change in the near future as more specific, direct inhibitors of virus replication are identified and better ways are developed for stimulating specific and nonspecific host defense mechanisms although the discussion of host defenses centered upon the interferon system, there are a variety of other nonspecific host defense mechanisms that are also important including macrophages, lymphocyte subpopulations, and other as yet poorly defined soluble mediators.

Topics: Acyclovir; Animals; Guanine; Humans; Immunity, Innate; Interferon Inducers; Interferons; Simplexvirus; Time Factors; Virus Diseases; Virus Replication

Topics: Acyclovir; Amantadine; Antiviral Agents; Bromodeoxyuridine; Clinical Trials as Topic; Guanine; Hepatitis B; Herpesviridae Infections; Humans; Interferons; Ketones; Neoplasms; Phosphonoacetic Acid; Vidarabine; Virus Diseases

Topics: Acyclovir; Adenine; Animals; Antiviral Agents; Arabinonucleosides; Bromodeoxyuridine; Chemical Phenomena; Chemistry; Cytarabine; Deoxyuridine; Guanine; Herpesviridae Infections; Humans; Idoxuridine; Nucleosides; Ribavirin; Thymidine; Virus Diseases; Viruses

Topics: Acyclovir; Animals; Antiviral Agents; Child; Guanine; Hepatitis B; Herpes Simplex; Humans; Interferons; Kidney Transplantation; Leukocytes; Nucleic Acid Synthesis Inhibitors; Protein Biosynthesis; RNA, Double-Stranded; RNA, Viral; Simplexvirus; Thymidine Kinase; Transplantation, Homologous; Virus Diseases; Virus Replication

Topics: Acyclovir; Bacterial Infections; Cytomegalovirus; Cytomegalovirus Infections; Female; Follow-Up Studies; Graft Rejection; Humans; Immunization, Passive; Immunoglobulins; Immunoglobulins, Intravenous; Incidence; Kidney Transplantation; Male; Opportunistic Infections; Retrospective Studies; Virus Diseases

Topics: Actuarial Analysis; Acyclovir; Adult; Cytomegalovirus Infections; Fever; gamma-Globulins; Ganciclovir; Graft Rejection; Humans; Immunosuppressive Agents; Liver Function Tests; Liver Transplantation; Postoperative Complications; Survival Analysis; Virus Diseases

Thus, we found that the role of Acyclovir in the treatment of viral corneal ulcer is definitely better and quicker. It takes less time for healing of corneal ulcer and as a result less hospitalisation is needed.

Topics: Acyclovir; Corneal Ulcer; Humans; Idoxuridine; Virus Diseases

We have described positive clinical effects of seven different anti-viral drugs in the treatment of viral respiratory diseases; three of these agents are approved for clinical use--amantadine, acyclovir, and vidarabine. Of the remaining four, the most consistent and broadest range of effect was observed with ribavirin while rimantadine was similar to amantadine in its effect. Interferon and enviroxime, under the conditions in which they were tested, showed a range of effect from moderate to no effect. A feature of the use of ribavirin was its administration by inhalation over several hour periods as a small-particle aerosol. This allowed a total dosage not much less than might have been given by other routes, but with the advantage that it was evenly deposited over the surface of the infected respiratory tract beginning within seconds of the start of treatment and reached higher concentration in nasal secretions than in serum. It may be that aerosol administration can be used with other drugs, as suggested by preliminary results with amantadine. We regard the results presented in this chapter as very encouraging, but just a beginning. Effective therapy will set in motion a reexamination of many problems of viral respiratory tract infection, including how to develop more rapid and more precise viral diagnosis, the need for further characterization of both short- and long-term consequences of infection in the untreated host and their modification by treatment. The structure for rapid progress in treatment of viral diseases is in place, and with it should come a resolution of many long-standing problems in this area of medicine.

Topics: Acyclovir; Adult; Amantadine; Animals; Antiviral Agents; Benzimidazoles; Child; Clinical Trials as Topic; Female; Humans; Influenza, Human; Interferons; Oximes; Pneumonia, Viral; Respiratory Tract Infections; Ribavirin; Rimantadine; Sulfonamides; Vidarabine; Virus Diseases

After a discussion of the principles of antiviral chemotherapy, treatment and chemoprophylaxis of the following virus infections are reviewed in detail: the various manifestations of herpes simplex virus infections, varicella-zoster, cytomegalovirus infections, Epstein-Barr virus infections, laryngeal papillomas, and influenza A. Special reference is made to the treatment of immunocompromized patients. Acycloguanosine (acyclovir) has been found particularly useful in the treatment of herpes simplex virus and varicella zoster virus infections in immunocompromized patients and for herpesencephalitis. Varicella-zoster can also be treated effectively with bromovinyldeoxyuridine (BVDU). Toxicity of the currently used antiviral drugs is discussed as well as the problem of drug resistance.

Topics: Acyclovir; Antiviral Agents; Bromodeoxyuridine; Chickenpox; Child; Clinical Trials as Topic; Cytomegalovirus Infections; Double-Blind Method; Encephalitis; Female; Herpes Genitalis; Herpes Simplex; Herpes Zoster; Humans; Immunologic Deficiency Syndromes; Infant, Newborn; Pemphigoid Gestationis; Pregnancy; Vidarabine; Virus Diseases

Antiviral compounds have been developed for use in chemoprophylaxis and chemotherapy of a variety of infections in humans, including those caused by influenza viruses, respiratory syncytial virus, and herpesviruses. The efficacy of several of these compounds has been demonstrated in rigorously controlled trials. Advances in molecular virology have led to the identification of biochemically defined, virus-specific functions that serve as appropriate targets for the future development of antiviral compounds. Clinical investigators and practicing physicians are now confronting questions previously raised with the use of antibacterial antibiotics. These questions concern appropriate routes of administration for antiviral compounds, optimal dosage regimens, risks of long-term prophylaxis, and the emergence of resistant organisms.

Topics: Acyclovir; Adult; Aged; Amantadine; Antiviral Agents; Chickenpox; Clinical Trials as Topic; Cytomegalovirus; Encephalitis; Foscarnet; Guanosine Triphosphate; Herpes Simplex; Herpes Zoster; Herpesviridae Infections; Humans; Infant, Newborn; Infant, Newborn, Diseases; Influenza A virus; Influenza, Human; Phosphonoacetic Acid; Respiratory Tract Infections; Ribavirin; Rimantadine; Vidarabine; Virus Diseases

Topics: Acyclovir; Amantadine; Antiviral Agents; Bone Marrow Transplantation; Chemical Phenomena; Chemistry; Clinical Trials as Topic; DNA, Viral; Herpesviridae; Herpesviridae Infections; Humans; Idoxuridine; Influenza A virus; Influenza, Human; Keratitis, Dendritic; RNA, Viral; S-Adenosylhomocysteine; Thymidine Kinase; Trifluridine; Vidarabine; Viral Proteins; Virus Diseases

Acyclovir (acycloguanosine) is a new antiviral compound with activity against certain herpes viruses. Acyclovir is phosphorylated preferentially in virus-infected cells into its active form, acyclovir triphosphate, an inhibitor of viral-induced DNA polymerase. Acyclovir, which possesses an acyclic carbohydrate moiety, also causes premature DNA chain termination. Acyclovir has shown clinical activity against herpes simplex virus (HSV) types 1 and 2 and varicella zoster virus (VZV), but its usefulness in cytomegalovirus, Epstein-Barr virus, and chronic hepatitis B infections requires further study. In randomized clinical trials of infections caused by HSV and VZV, intravenous acyclovir has been shown to shorten the duration of viral shedding and lesion pain and hasten the resolution of skin lesions, with minimal toxicity.

Topics: Acyclovir; Clinical Trials as Topic; Cytomegalovirus Infections; Drug Resistance, Microbial; Herpes Simplex; Herpes Zoster; Humans; Injections, Intravenous; Kinetics; Virus Diseases

Topics: Acyclovir; Amantadine; Antiviral Agents; Bromodeoxyuridine; Clinical Trials as Topic; Guanine; Hepatitis B; Herpesviridae Infections; Humans; Interferons; Ketones; Neoplasms; Phosphonoacetic Acid; Vidarabine; Virus Diseases

Viral infections kill millions of people and new antivirals are needed. Nontoxic drugs that irreversibly inhibit viruses (virucidal) are postulated to be ideal. Unfortunately, all virucidal molecules described to date are cytotoxic. We recently developed nontoxic, broad-spectrum virucidal gold nanoparticles. Here, we develop further the concept and describe cyclodextrins, modified with mercaptoundecane sulfonic acids, to mimic heparan sulfates and to provide the key nontoxic virucidal action. We show that the resulting macromolecules are broad-spectrum, biocompatible, and virucidal at micromolar concentrations in vitro against many viruses [including herpes simplex virus (HSV), respiratory syncytial virus (RSV), dengue virus, and Zika virus]. They are effective ex vivo against both laboratory and clinical strains of RSV and HSV-2 in respiratory and vaginal tissue culture models, respectively. Additionally, they are effective when administrated in mice before intravaginal HSV-2 inoculation. Lastly, they pass a mutation resistance test that the currently available anti-HSV drug (acyclovir) fails.

Topics: Acyclovir; Animals; Antiviral Agents; Cyclodextrins; Female; Gold; Heparitin Sulfate; Herpesvirus 1, Human; Herpesvirus 2, Human; Humans; Metal Nanoparticles; Mice; Simplexvirus; Virus Diseases; Zika Virus

Topics: Acute Disease; Acyclovir; Adult; Anti-Bacterial Agents; Antiviral Agents; Bacterial Infections; Cephalosporins; Ciprofloxacin; Female; Humans; Male; Pancreatitis; Retrospective Studies; Tertiary Care Centers; Treatment Outcome; Virus Diseases

In this study, we demonstrated that cationic liposomes with incorporated stearylamine (SA) inhibit viral infectivity without preloaded active pharmaceutical ingredients. Specifically, we correlated physiochemical properties of liposomes, such as zeta potentials and particle sizes, with virus infectivity using the BacMam™ reagent, which is based on recombinant baculovirus (BV). Compared with neutral or negatively-charged liposomes, SA liposomes suppressed BV infectivity in several mammalian cell lines, including A549 cells. SA liposomes inhibited BV infection over 80% by optimizing the liposomal concentration and exposure time with cells. Moreover, these antiviral SA liposomes were not cytotoxic, and reducing the embedded cholesterol contents intensified the antiviral effects and simultaneously increased the binding of SA liposomes to the cell membranes. These data indicate that binding of SA liposomes to cell membranes may block virus entry. Finally, we also demonstrated the antiviral effects of SA liposomes on herpes simplex virus type 1 in A549 cells, and showed comparable efficacy to that of the antiviral drug acyclovir.

Topics: A549 Cells; Acyclovir; Amines; Animals; Antiviral Agents; Baculoviridae; Cations; Cell Survival; Chlorocebus aethiops; Herpesvirus 1, Human; Host-Pathogen Interactions; Humans; Liposomes; Vero Cells; Viral Plaque Assay; Virus Diseases

Three-dimensional (3D) in vitro tissue models provide an approach for the systematic, repetitive, and quantitative study of drugs. In this study, we constructed an in vitro 3D acrylated hyaluronic acid (AHA) hydrogel model encapsulating fibroblasts, performed long-period 3D culture, and tested cellular topological changes and proliferation variation in the presence of herpes simplex virus-1 (HSV-1) as an infecting virus and acyclovir (ACV) as the treatment drug. The AHA hydrogels were formed by using Michael addition chemistry of bis-cysteine containing MMP-degradable cross-linker onto AHA prefunctionalized with cell adhesion peptides (RGD). Cellular structures of 3T3 fibroblasts in hydrogel presented different morphological evolution processes and proliferation rates between different groups, including HSV-1 treated alone, ACV treated alone, HSV-1 and ACV cotreated, and control samples. In AHA hydrogel, ACV blocked HSV-1 infection/replication on fibroblasts. Yet, the proliferation of ACV-treated fibroblasts was slower than that of the control group. A significantly longer period was required for cells in 3D AHA gel to regain a healthy status when compared with cells in two-dimensional (2D) culture. This hydrogel-based 3D culture model potentially lays a foundation for analyzing the response of self-organized 3D tissues to viruses and drugs in a way that is closer to nature.

Topics: Acyclovir; Animals; Antiviral Agents; Cell Adhesion; Cell Line; Cell Proliferation; Fibroblasts; Herpes Simplex; Herpesvirus 1, Human; Hyaluronic Acid; Hydrogels; Mice; NIH 3T3 Cells; Virus Diseases

Herpes simplex virus (HSV) laryngitis is rare in adults. We add a case report to the literature and perform a literature review to further delineate the clinical presentation, course, and treatment of HSV laryngitis in adults.. Case report and literature review using PubMed and Ovid databases.. Ten cases of diagnosed HSV laryngitis in adults were reported in the literature. It is more common in immunocompromised patients. The mean patient age was 51 years with a male to female ratio of 1:1. The clinical presentation and course of HSV laryngitis is variable. Patients may have mild chronic symptoms, such as dysphonia, or a fulminant course with rapid airway compromise. On laryngoscopic exam, the most common findings are a white exudate or ulceration. The most common treatment is with antiviral medication, such as acyclovir, which tends to be highly effective.. Herpes simplex virus laryngitis is rare. Clinical presentation of HSV laryngitis is variable, and its course may be indolent or fulminant. Treatment with antiviral medication tends to be highly effective.

Topics: Acyclovir; Administration, Intravenous; Aged; Airway Obstruction; Antiviral Agents; Female; Herpesvirus 1, Human; Herpesvirus 2, Human; Humans; Laryngitis; Laryngoscopy; Respiration, Artificial; Treatment Outcome; Virus Diseases

We describe two young immunocompetent women presenting with bilateral retinitis with outer retinal necrosis involving posterior pole with centrifugal spread and multifocal lesions simulating progressive outer retinal necrosis (PORN) like retinitis. Serology was negative for HIV and CD4 counts were normal; however, both women were on oral steroids at presentation for suspected autoimmune chorioretinitis. The retinitis in both eyes responded well to oral valaciclovir therapy. However, the eye with the more fulminant involvement developed retinal detachment with a loss of vision. Retinal atrophy was seen in the less involved eye with preservation of vision. Through these cases, we aim to describe a unique evolution of PORN-like retinitis in immunocompetent women, which was probably aggravated by a short-term immunosuppression secondary to oral steroids.

Topics: Acyclovir; Adolescent; Antiviral Agents; Chorioretinitis; Female; Humans; Immunocompetence; Retinal Necrosis Syndrome, Acute; Steroids; Tomography, Optical Coherence; Valacyclovir; Valine; Virus Diseases; Vision Disorders; Young Adult

Bloodstream infections (BSIs) and central line infections remain among the major causes of morbidity and mortality in transplant recipients because of prolonged neutropenia and mucosal damage. The objective of this study was to determine the frequency and outcome of bacterial and fungal isolates from patients undergoing allogeneic hematopoietic stem cell transplant.. This study was conducted at the Aga Khan University and Hospital's bone marrow transplant unit. All patients who underwent an allogeneic stem cell transplant with matched sibling/parent donor were included. The study period ranged from April 2004 to December 2012. Transplantation was performed according to institutional protocols. All patients were admitted in single rooms with positive pressure and high-efficiency particulate air filters. Ciprofloxacin, fluconazole, and valaciclovir were used for standard prophylaxis, which was started at the time of conditioning. All blood cultures were obtained at clinical suspicion of systemic infection, mainly documented as fever (temperature of >38.5°C). BSIs and line infections were defined as isolation of bacterial or fungal pathogen from at least one blood/central line culture.. In total, 101 of 108 patients developed febrile neutropenia. In the 101 patients, 245 documented febrile episodes occurred. There were 40 culture-positive episodes and 205 culture-negative episodes. Of these 40 culture-positive episodes, 22 patients had bloodstream isolates and 18 had central line isolates. The median ± standard deviation time of febrile neutropenia was day 7 ± 2 days (range: day -3 to day +13). The most common bloodstream isolate was Escherichia coli (n = 9) followed by Staphylococcus epidermidis (n = 5). One patient developed Fusarium infection. In central line infections, S. epidermidis was the most common organism (n = 8). In 2 patients with central venous catheters, Candida albicans was the isolate. Transplant-related mortality from sepsis occurred in 9.2%.. E.coli was mainly responsible for BSI, while gram-positive organisms dominated catheter-related febrile episodes. Transplant-related mortality due to sepsis was 9%.

Topics: Acyclovir; Adolescent; Adult; Anti-Infective Agents; Bacteremia; Candida albicans; Candidiasis; Catheterization, Central Venous; Catheters, Indwelling; Child; Child, Preschool; Ciprofloxacin; Developing Countries; Escherichia coli; Escherichia coli Infections; Febrile Neutropenia; Female; Fluconazole; Fungemia; Fusariosis; Fusarium; Hematopoietic Stem Cell Transplantation; Humans; Male; Middle Aged; Pakistan; Retrospective Studies; Staphylococcal Infections; Staphylococcus epidermidis; Valacyclovir; Valine; Virus Diseases; Young Adult

Biotinylated lipid prodrugs of acyclovir (ACV) were designed to target the sodium dependent multivitamin transporter (SMVT) on the cornea to facilitate enhanced cellular absorption of ACV.. All the prodrugs were screened for in vitro cellular uptake, interaction with SMVT, docking analysis, cytotoxicity, enzymatic stability and antiviral activity.. Uptake of biotinylated lipid prodrugs of ACV (B-R-ACV and B-12HS-ACV) was significantly higher than biotinylated prodrug (B-ACV), lipid prodrugs (R-ACV and 12HS-ACV) and ACV in corneal cells. Transepithelial transport across rabbit corneas indicated the recognition of the prodrugs by SMVT. Average Vina scores obtained from docking studies further confirmed that biotinylated lipid prodrugs possess enhanced affinity towards SMVT. All the prodrugs studied did not cause any cytotoxicity and were found to be safe and non-toxic. B-R-ACV and B-12HS-ACV were found to be relatively more stable in ocular tissue homogenates and exhibited excellent antiviral activity.. Biotinylated lipid prodrugs demonstrated synergistic improvement in cellular uptake due to recognition of the prodrugs by SMVT on the cornea and lipid mediated transcellular diffusion. These biotinylated lipid prodrugs appear to be promising drug candidates for the treatment of herpetic keratitis (HK) and may lower ACV resistance in patients with poor clinical response.

Topics: Acyclovir; Animals; Antiviral Agents; Biotinylation; Cell Line; Cells, Cultured; Cornea; Humans; Molecular Docking Simulation; Prodrugs; Rabbits; Symporters; Virus Diseases; Viruses

Acyclovir (ACV) as a model antiviral microbicide, was incorporated in controlled-release polycaprolactone (PCL) matrices designed for application as intra-vaginal ring inserts (IVRs). Microporous materials incorporating acyclovir up to a level of ~10 % w/w were produced by rapidly cooling suspensions of drug powder in PCL solution followed by solvent extraction from the hardened matrices. Around 21, 50 and 78 % of the drug content was gradually released from matrices over 30 days in simulated vaginal fluid at 37 °C, corresponding to drug loadings of 5.9, 7.0 and 9.6 % w/w. The release behaviour of matrices having the lowest drug loading followed a zero order model, whereas, the release kinetics of 7.0 and 9.6 % ACV-loaded PCL matrices could be described effectively by the Higuchi model, suggesting that Fickian diffusion is controlling drug release. Corresponding values of the diffusion co-efficient for ACV in the PCL matrices of 3.16 × 10(-9) and 1.07 × 10(-8) cm(2)/s were calculated. Plaque reduction assays provided an IC50 value of 1.09 μg/mL for acyclovir against HSV-2 and confirmed the antiviral activity of released acyclovir against HSV-2 replication in primate kidney cells (Vero) at levels ~70 % that of non-formulated acyclovir at day 30. Estimated minimum in vivo acyclovir concentrations produced by a PCL IVR (19 μg/mL) exceeded by a factor of 20 the IC50 value against HSV-2 and the reported ACV vaginal concentrations in women (0.5-1.0 μg/mL) following oral administration. These findings recommend further investigations of PCL matrices for vaginal delivery of antiviral agents in the treatment and prevention of sexually transmitted infections such as AIDS.

Topics: Acyclovir; Administration, Intravaginal; Antiviral Agents; Delayed-Action Preparations; Drug Delivery Systems; Female; Hardness; Herpesvirus 2, Human; Humans; Inhibitory Concentration 50; Materials Testing; Polyesters; Solvents; Vagina; Virus Diseases

We describe the case of a 19-year-old male diagnosed with Reye syndrome within the context of viral pericarditis and salicylate ingestion. He presented a fatal brain oedema without liver failure. Brain biopsies obtained during a decompressive craniectomy led to the diagnosis.

Topics: Acyclovir; Anti-Inflammatory Agents, Non-Steroidal; Antiviral Agents; Aspirin; Brain Edema; Coma; Decompressive Craniectomy; Fatal Outcome; Glasgow Coma Scale; Humans; Magnetic Resonance Imaging; Male; Pericarditis; Resuscitation; Reye Syndrome; Seizures; Virus Diseases; Young Adult

Series of novel acyclic nucleoside phosphonates (ANPs) with various nucleobases and 2-(2-phosphonoethoxy)ethyl (PEE) chain bearing various substituents in β-position to the phosphonate moiety were prepared. The influence of structural alternations on antiviral activity was studied. Several derivatives exhibit antiviral activity against HIV and vaccinia virus (middle micromolar range), HSV-1 and HSV-2 (lower micromolar range) and VZV and CMV (nanomolar range), although the parent unbranched PEE-ANPs are inactive. Adenine as a nucleobase and the methyl group attached to the PEE chain proved to be a prerequisite to afford pronounced antiviral activity.

Topics: Animals; Antiviral Agents; Cell Line; Cell Survival; Herpes Simplex; HIV; HIV Infections; Humans; Mice; Nucleosides; Organophosphonates; Simplexvirus; Structure-Activity Relationship; Vaccinia; Vaccinia virus; Virus Diseases; Viruses

Lymphoma after heart transplantation (HT) has been associated with induction therapy and herpesvirus infection. It is not known whether anti-viral agents administered immediately after HT can reduce the incidence of lymphoma.. This study was a retrospective review of 3,393 patients who underwent HT in Spain between 1984 and December 2003. Variables examined included development of lymphoma and, as possible risk factors, recipient gender and age, induction therapies (anti-thymocyte globulin, OKT3 and anti-interleukin-2 receptor antibodies) and anti-viral prophylaxis (acyclovir or ganciclovir). To study the effect of evolving treatment strategy, three HT eras were considered: 1984 to 1995; 1996 to 2000; and 2001 to 2003.. Induction therapy was employed in >60% of HTs, and anti-viral prophylaxis in >50%. There were 62 cases of lymphoma (3.1 per 1,000 person-years, 95% confidence interval: 2.4 to 4.0). Univariate analyses showed no influence of gender, age at transplant, HT era, pre-HT smoking or the immunosuppressive maintenance drugs used in the first 3 months post-HT. The induction agent anti-thymocyte globulin (ATG) was associated with increased risk of lymphoma, and prophylaxis with acyclovir with decreased risk of lymphoma. Multivariate analyses (controlling for age group, gender, pre-HT smoking and immunosuppression in the first 3 months with mycophenolate mofetil and/or tacrolimus) showed that induction increased the risk of lymphoma if anti-viral prophylaxis was not used (regardless of induction agent and anti-viral agent), but did not increase the risk if anti-viral prophylaxis was used.. Induction therapies with ATG or OKT3 do or do not increase the risk of lymphoma depending on whether anti-viral prophylaxis with acyclovir or ganciclovir is or is not employed, respectively.

Topics: Acyclovir; Adult; Antilymphocyte Serum; Antiviral Agents; Female; Ganciclovir; Heart Transplantation; Humans; Immunosuppressive Agents; Lymphoma; Male; Middle Aged; Multivariate Analysis; Muromonab-CD3; Registries; Retrospective Studies; Risk Factors; Spain; Virus Diseases

Topics: Acyclovir; Adult; Antiviral Agents; Humans; Immunocompromised Host; Valacyclovir; Valine; Virus Diseases

Topics: 2-Aminopurine; Acyclovir; Antiviral Agents; Cytomegalovirus Infections; Drug Resistance, Viral; Famciclovir; Guanine; Hepatitis B; Hepatitis C; Herpes Simplex; Herpes Zoster; Humans; Influenza, Human; Valacyclovir; Valine; Virus Diseases

We report here a patient who suffered from PCR- confirmed human herpesvirus type 6 (HHV-6) meningoencephalitis after allogeneic purified CD34+ cell transplantation from his HLA-mismatched sibling donor, even though he had been on intense prophylaxis with i.v. ganciclovir (GCV), acyclovir (ACV) and gamma-globulin containing a specific antibody against HHV-6. Serological evaluation disclosed that both the donor and recipient had IgG antibody against HHV-6 before transplantation. His blood WBC count started to transiently increase on day 10, and all blood components had decreased by day 20. He then developed a severe headache and high blood pressure, and sporadic abnormal neurological findings including nystagmus and delirium. An analysis of cerebrospinal fluid (CSF) revealed 8 cells/microl, a glucose level of 130 mg/dl and a protein level of 201 mg/dl (normal, 50 mg/dl) on day 26. At the time, HHV-6 was detected only in CSF by a PCR-based method and he was diagnosed as having meningoencephalitis due to the local reactivation of HHV-6. Although he failed to respond to high-dose therapy with ACV (60 mg/kg/day) and gamma-globulin, the DNA of this virus disappeared from the CNS upon treatment with GCV (30 mg/kg/day) combined with the intraventricular infusion of alpha-interferon. His clinical course was further complicated with meningoencephalitis due to staphylococcus epidermidis, and he died of tentorial herniation on day 79 without the recovery of blood components. This experience may indicate that intense prophylaxis to prevent reactivation of HHV-6 in the CNS is essential for the management of such profoundly immunosuppressed patients.

Topics: Acyclovir; Adolescent; Anemia, Aplastic; Antigens, CD; Antigens, CD34; Antiviral Agents; Drug Therapy, Combination; gamma-Globulins; Ganciclovir; Hematopoietic Stem Cell Transplantation; Herpesviridae Infections; Herpesvirus 6, Human; Histocompatibility Testing; Humans; Magnetic Resonance Imaging; Male; Meningoencephalitis; Polymerase Chain Reaction; Virus Diseases

Synthesis and preliminary biological evaluation of 9-(4-[18F]-fluoro-3-hydroxymethylbutyl)-guanine ([18F]FHBG) is reported. 9-(4-Hydroxy-3-hydroxymethylbutyl)-guanine (penciclovir) 4 was converted to 9-[N2, O-bis-(methoxytrityl)-3-(tosylmethybutyl)]guanine 7 by treatment with methoxytrityl chloride followed by tosylation. The tosylate 7 was reacted with either tetrabutylammonium fluoride or KF in the presence of kryptofix 2.2.2. to produce the 4-fluoro-N2-O-bis-(methoxytrityl) derivative 8. Removal of the methoxytrityl groups by acidic hydrolysis produced FHBG 5. Radiolabeled product [18F]FHBG was prepared by fluorination of the tosylate 7 with [18F]KF and kryptofix 2.2.2. The labeled product was isolated by HPLC purification on a reverse-phase C18 column, and eluted at 12 min with 15% acetonitrile in water at a flow rate of 2.25 mL/min. Radiochemical yield was 8.0-22.3% with an average of 12% in 7 runs (corrected for decay). Synthesis time was 90 to 100 min including HPLC purification with radiochemical purity >99%, and average specific activity of 320 mCi/micromol. In vitro studies of the compound in HT-29 colon cancer cells revealed 18.2-fold higher uptake into transduced cells compared to control in 3 h. The agent may be useful for imaging viral infection or transfected cells in gene therapy.

Topics: Acyclovir; Antiviral Agents; Biological Transport; Colonic Neoplasms; Fluorine Radioisotopes; Genetic Therapy; Guanine; Humans; Indicators and Reagents; Molecular Structure; Radionuclide Imaging; Tumor Cells, Cultured; Virus Diseases

EEG has been used widely in diagnosing encephalitis, as it demonstrates rather typical abnormalities, especially in herpes simplex virus encephalitis (HSVE). We analysed 204 EEG recordings from 98 consecutive acyclovir-treated patients with acute encephalitis between 1984 and 1994. Periodic complexes (PC) in the acute phase predicted poor outcome (Kendall tau 0.40, P < 0.001). However, unlike in many other diseases, e.g. stroke and intracerebral haemorrhage, the diffuse slowing of the background activity at acute phase did not predict outcome (Kendall tau -0.6, P = 0.35). At follow-up, the emergence of diffuse slow background activity was significantly associated with a less favourable outcome (Kendall tau 0.33, P = 0.0016). Among clinical variables, only epileptic seizures early during the course of the disease correlated significantly with outcome. EEG does have value as a prognostic indicator in acute encephalitides, but it seems that diffuse slowing of background activity or irritative features acutely are not as important as previously thought, based on the experiences of the pre-acyclovir era.

Topics: Acute Disease; Acyclovir; Adult; Antiviral Agents; Electroencephalography; Encephalitis; Female; Herpes Simplex; Humans; Male; Middle Aged; Regression Analysis; Treatment Outcome; Virus Diseases

Topics: 2-Aminopurine; Abnormalities, Drug-Induced; Acyclovir; Amantadine; Antiviral Agents; Cidofovir; Contraindications; Cytosine; Drug Resistance, Microbial; Eye Infections, Viral; Famciclovir; Foscarnet; Ganciclovir; Guanine; Humans; Interferon-alpha; Kidney Diseases; Lamivudine; Organophosphonates; Organophosphorus Compounds; Prodrugs; Ribavirin; Rimantadine; Trifluridine; Valacyclovir; Valine; Virus Diseases

Topics: Acyclovir; Antiviral Agents; Drug Resistance, Microbial; Humans; Virus Diseases

Acute neurotoxicity following the administration of the recommended oral dose of acyclovir (800 mg twice daily) to dialysis-dependent patients is increasingly recognised. This suggests that the recommended dose is too high. Little is known of the pharmacokinetics of oral acyclovir in dialysis patients. We studied 7 patients with oliguric end stage renal failure receiving haemodialysis. Following haemodialysis, each patient received a single 800-mg tablet of acyclovir. Plasma acyclovir levels were monitored over the next 48 h as well as before and after the next routine dialysis. Peak plasma levels were achieved at 3 h (12.54 +/- 1.76 microM, range 8.5-17.5 microM) with the half-life calculated to be 20.2 +/- 4.6 h. Mean plasma level of 6.29 +/- 0.94 microM were within the quoted range to inhibit herpes zoster virus (4-8 microM) at 18 h. Haemodialysis (4-5 h) eliminated 51 +/- 11.5% of the acyclovir which remained at 48 h. Computer modelling of various dose modifications suggests that a loading dose of 400 mg and a maintenance dose of 200 mg twice daily is sufficient to maintain a mean plasma acyclovir level of 6.4 +/- 0.8 microM. A further loading dose (400 mg) after dialysis would raise the residual acyclovir concentration by 6.1 +/- 1.0 microM. Such a dose modification should prevent neurotoxicity, whilst the rapid elimination of acyclovir by a single haemodialysis treatment provides both a diagnostic and therapeutic tool when toxicity is suspected.

Topics: Acyclovir; Administration, Oral; Adult; Aged; Computer Simulation; Female; Half-Life; Humans; Kidney Failure, Chronic; Male; Middle Aged; Nervous System; Renal Dialysis; Virus Diseases

Topics: Acyclovir; Adolescent; Anti-Bacterial Agents; Bacterial Infections; Child; Child, Preschool; Cytomegalovirus Infections; Drug Therapy, Combination; Follow-Up Studies; Humans; Infant; Intestine, Small; Liver Transplantation; Male; Pneumonia, Pneumocystis; Postoperative Complications; Sulfamethoxazole; Surgical Wound Infection; Time Factors; Trimethoprim; Virus Diseases

Topics: Acyclovir; Amantadine; Antiviral Agents; Drug Resistance, Microbial; Foscarnet; Ganciclovir; Humans; Interferon-alpha; Ribavirin; Rimantadine; Virus Diseases

Topics: Acyclovir; Female; Fetus; Humans; Infant, Newborn; Pregnancy; Pregnancy Complications, Infectious; Virus Diseases

Topics: Acyclovir; Herpesviridae Infections; Humans; Virus Diseases; Virus Replication

Topics: Acyclovir; Antiviral Agents; Drug Resistance; Foscarnet; Humans; Immunocompromised Host; Phosphonoacetic Acid; Rimantadine; Virus Diseases; Zidovudine

Topics: Acyclovir; Encephalitis; Humans; Virus Diseases

This investigation examines whether cytokines, as exemplified by leukoregulin, with their immense potential for biorecognition and target cell modulation as a result of their complex three-dimensional structure, have the potential to provide new directions for biotherapy of infectious disease. Leukoregulin is a naturally occurring immunologic cytokine, secreted by stimulated lymphocytes, which increases membrane permeability and drug uptake in tumor but not in normal cells. This study demonstrates that leukoregulin also increases the plasma membrane permeability of cells acutely infected with herpes simplex type 1 virus and that the increase in membrane permeability is accompanied by a 10- to 100-fold increase in the ability of acyclovir to inhibit the release of infectious virus when the cells are treated with leukoregulin 3 hours after infection with the virus. This is the first demonstration that a cytokine, alone or in combination with anti-viral chemotherapy, can effectively inhibit virus replication in human cells following acute virus infection, which indicates that combination immunotherapy and chemotherapy have the potential to completely inhibit the production of infectious virus by acutely infected human cells.

Topics: Acyclovir; Adolescent; Animals; Antineoplastic Agents; Antiviral Agents; Cell Membrane Permeability; Cytokines; Drug Synergism; Drug Therapy, Combination; Female; Guinea Pigs; Humans; Lymphokines; Simplexvirus; Tumor Cells, Cultured; Virus Diseases; Virus Replication

Three observations of typical patients with persistent and recurrent nummuli after epidemic keratoconjunctivitis serve--pars pro toto--to demonstrate that longterm therapy with high-dosed topical steroid offers no therapeutic solution. This experience and other disadvantages of steroids in KCE (dry eyes) lead us to recommend not to apply topical steroids in KCE unless an adenovirus specific antiviral agent has become available for basic antiviral therapy.

Topics: Acyclovir; Adult; Cornea; Dose-Response Relationship, Drug; Female; Humans; Keratoconjunctivitis; Male; Ophthalmic Solutions; Prednisolone; Virus Diseases; Visual Acuity

A series of aryl bis(3'-O-acetylthymidin-5'-yl) phosphate derivatives have been synthesized in order to find a suitable aryl derivative which would hydrolyze to the bis(nucleosid-5'-yl) phosphate under physiological conditions. The 4-(methylsulfonyl)phenyl derivative was selected and 4-(methylsulfonyl)phenyl bis[(E)-5-(2-bromovinyl)-2'-deoxyuridin-5'-yl] phosphate (6d) and bis[2-(guanin-9-ylmethoxy)ethoxy]-4-(methylsulfonyl)phenyl phosphate (7b) were prepared. The former compound (6d) was stable in human serum and only following hydrolysis to the 5'-5'-linked diester (half-life of 17 h at pH 7.7) was it enzymatically degraded very rapidly by phosphodiesterases. Compounds 6d and 7b were evaluated for antiherpesvirus effects, both in vitro and in vivo. Their antiviral spectrum and potency was remarkably similar to that of (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVDU) and 9-[(2-hydroxyethoxy)-methyl]guanine (ACV), suggesting that they only act as prodrugs of BVDU and ACV, respectively. However, compound 6d did show unexpected toxicity, which could be explained by the liberation of BVDUMP following penetration of the triester into the cell.

Topics: Acyclovir; Animals; Antiviral Agents; Cells, Cultured; Chemical Phenomena; Chemistry; Deoxyuracil Nucleotides; HIV Infections; Mice; Prodrugs; Rabbits; Structure-Activity Relationship; Virus Diseases

Topics: Acyclovir; Amantadine; Antiviral Agents; Ganciclovir; Humans; Interferon Type I; Recombinant Proteins; Virus Diseases; Zidovudine

Over three years 81 consecutive bone marrow transplant recipients (32 allogeneic and 49 autologous) who received prophylaxis with acyclovir, were studied for symptomatic virus infection. Thirty nine infections were documented in a total of 28 patients. Thirty two infections were mild, five were moderately severe, and two were severe. Cytomegalovirus infection occurred in only six allogeneic recipients. Herpes simplex virus and varicella zoster virus infections occurred infrequently. Seven patients who were considered at the time of death to have died due to an infectious cause were studied virologically at necropsy. In only one patient was a virus infection thought to have been the cause of death. Prophylaxis with acyclovir may have influenced the rate and clinical prominence of herpes virus infections. In this study viruses were considered to have had a relatively minor role in causing morbidity and mortality.

Topics: Acyclovir; Adolescent; Adult; Bone Marrow Transplantation; Child; Child, Preschool; Graft vs Host Disease; Humans; Middle Aged; Postoperative Complications; Prospective Studies; Virus Diseases

From November 1985 to August 1987, 22 children underwent orthotopic liver transplantation (OLT). Primary cytomegalovirus (CMV) infection was observed in 3 of 10 seronegative recipients (30%). It was severe in 2 cases, which were treated successfully by a combination of DHPG and CMV hyperimmune globulin. From September 1987 to August 1988, a virologic survey was undertaken. It enabled us to take prophylactic measures and to make an early diagnosis of CMV infection, permitting early antiviral treatment. During this period, 26 children received liver grafts. Nine of 13 seronegative recipients (69, 2%) developed primary CMV infection. Seven had received immunoprophylaxis and 8 were treated by DHPG. None had severe disease and all improved rapidly.

Topics: Acyclovir; Antibodies, Viral; Child; Child, Preschool; Cytomegalovirus Infections; Humans; Immunization, Passive; Liver Transplantation; Prospective Studies; Virus Diseases

Pathologic changes in the skin of elderly individuals increase their susceptibility to skin infections. These changes include thinning, decreased secretions, and reduced immune function. This paper will discuss the most important viral, fungal, bacteriologic, and parasitic infections of the skin in the elderly and the appropriate treatment of these infections.

Topics: Acyclovir; Aged; Anti-Bacterial Agents; Antifungal Agents; Antiparasitic Agents; Dermatomycoses; Diagnosis, Differential; Humans; Middle Aged; Skin Diseases, Infectious; Skin Diseases, Parasitic; Virus Diseases

Topics: Acyclovir; Adult; Child; Drug Therapy, Combination; Encephalitis; Female; Humans; Interferons; Male; Middle Aged; Vidarabine; Virus Diseases

Of 33 patients with viral encephalitis, four (three women, one man) succumbed to the disease. Of the surviving patients, 23 were followed for a median interval of 4 years after discharge. A considerable residual syndrome could be detected in two cases only. The outcome was determined by identification of causative organism (especially herpes simplex virus), initial consciousness disturbances and pleocytosis in the cerebrospinal fluid. On the other hand, the age of the patients, electroencephalographic findings and a symptomatic epilepsy played no major role. Without confirmed virus findings, immunoglobulins were as effective as the virostatic therapy regimens; with identification of causative organism, combined treatment with acyclovir and immunoglobulins was most effective.

Topics: Acyclovir; Adult; Aged; Antibodies, Viral; Encephalitis; Female; Humans; Male; Mental Disorders; Middle Aged; Prognosis; Retrospective Studies; Time Factors; Tomography, X-Ray Computed; Virus Diseases

Topics: Acyclovir; Humans; Virus Diseases

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Antiviral Agents; Cytomegalovirus; DNA, Viral; Drug Resistance, Microbial; Herpesvirus 3, Human; Herpesvirus 4, Human; HIV; Humans; Interferons; Nucleosides; Reverse Transcriptase Inhibitors; Ribavirin; RNA, Messenger; RNA, Viral; Simplexvirus; Thymidine; Virus Diseases; Virus Physiological Phenomena; Virus Replication; Zidovudine

Viral infections, predominantly those of the herpes virus family, account for up to 16% of all clinically significant infections in AIDS patients. Acyclovir has provided successful treatment in AIDS patients suffering from severe herpes simplex and herpes zoster virus infections. Preliminary results are presented on newly developed acyclovir analogues. Desciclovir, an oral prodrug of acyclovir which is metabolized to acyclovir in vivo, allows treatment of virus infections per os, where high serum levels are needed, e.g. in Epstein-Barr virus infections. BW B759U, another analogue of acyclovir, has been used for the treatment of life-threatening or sight-threatening cytomegalovirus infections in AIDS patients. More than 80% of the patients treated for retinitis experienced stabilization or clinical improvement. Antiviral efficacy was demonstrated in 73% of the patients. Azidothymidine, a nucleoside analogue of thymidine, has been developed specifically to treat the HIV infection. Its antiviral activity is based on inhibition of reverse transcriptase. Phase I studies have demonstrated that azidothymidine is well tolerated. Its ability to cross the blood brain barrier makes it an attractive candidate for treatment of HIV. Trials to determine efficacy are in progress.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Antiviral Agents; Cytomegalovirus Infections; Herpes Simplex; Herpes Zoster; Herpesvirus 4, Human; Humans; Leukoplakia, Oral; Opportunistic Infections; Thymidine; Tumor Virus Infections; Virus Diseases; Zidovudine

Topics: Acute Disease; Acyclovir; Adult; Esophagitis; Esophagoscopy; Female; Humans; Immune Tolerance; Male; Virus Diseases

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Amantadine; Antiviral Agents; Chickenpox; Common Cold; Cytomegalovirus Infections; Herpes Simplex; Herpes Zoster; Herpesviridae Infections; Herpesvirus 4, Human; Humans; Influenza, Human; Interferons; Ribavirin; Rimantadine; Thymidine; Vidarabine; Virus Diseases; Zidovudine

Topics: Acyclovir; Amantadine; Antiviral Agents; Common Cold; Herpesviridae Infections; Humans; Interferons; Respiratory Tract Infections; Respirovirus Infections; Ribavirin; Virus Diseases

Considerable progress has been made in the supportive care of patients undergoing cancer therapy. This progress has been associated with the improved survival of some patients. However, infection continues to be the major fatal complication in cancer. patients. The response of granulocytopenic patients with infections to some of the current available antibiotics is suboptimal. Since neutropenia is common during cancer treatment, there is a continual risk of infection in cancer patients; thus it is important for medical oncologists to become aware of these complications and their management. The most frequent types of acute infections, their clinical manifestations, and available antibiotic therapies were reviewed.

Topics: Acyclovir; Anti-Bacterial Agents; Bacterial Infections; Fever; Humans; Leukemia, Lymphoid; Leukemia, Myeloid; Neoplasms; Neutropenia; Vidarabine; Virus Diseases

It has been postulated that Behçet's disease may be a viral induced vasculitis. In the present study plasma exchanges were applied in an attempt to remove circulating immune complexes and restore cellular immunity. High doses of acyclovir were administered in association with plasma exchanges since it has been shown that herpes simplex virus type 1 might be involved in Behçet's vasculitis. Seven patients with severe ocular manifestations of Behçet's disease were selected for the study. Plasma exchanges were carried out at the rate of 3 per week during 3 weeks and then once every two weeks during 3 months followed by 1 per month during 3 months. 45 mg/day/kg acyclovir were administered intravenously for 21 days. At the end of the follow-up period comparative analysis of panretinal fluorescein angiographies before and after treatment showed no change of the fundus lesions in 3 patients, improvement in only 2 patients and significant worsening in 2 patients. The rather negative results of the present trial lead to assume that HSV-1 is not the virus involved, if any, in Behçet's disease. On the other hand, in the present study, the efficiency of plasma exchanges was transient.

Topics: Acyclovir; Adult; Antigen-Antibody Complex; Behcet Syndrome; Combined Modality Therapy; Female; Fluorescein Angiography; Humans; Male; Middle Aged; Plasma Exchange; Prospective Studies; Vasculitis; Virus Diseases; Visual Acuity

Opportunistic viral infections were investigated in 156 adult patients admitted over one year to a medical oncology service: 35% of the total group and 65% of those with acute leukaemia experienced viral infections, 79% of which were with viruses of the herpes group. Surprisingly few enteric viruses were recovered. Reactivation of herpes simplex virus in the brains of these immunosuppressed patients was suggested by the demonstration by nucleic acid hybridization of herpes simplex virus DNA sequences in neurones and endothelial cells in patients with evidence of past infection with virus. Acyclovir was effective in therapy and prophylaxis. Twenty-three strains from 7 patients were tested for sensitivity to this antiviral: in 3 instances clinical resistance was observed but the strains were fully sensitive in vitro, as were all other strains tested.

Topics: Acyclovir; Adult; Brain; Breast Neoplasms; Bronchial Neoplasms; DNA, Viral; Herpes Simplex; Humans; Immunosuppression Therapy; Leukemia, Lymphoid; Leukemia, Myeloid; Lymphoma; Nucleic Acid Hybridization; Simplexvirus; Virus Diseases

Topics: Acyclovir; Bacterial Infections; Cryptococcosis; Cytomegalovirus Infections; Drug Combinations; Humans; Infection Control; Infections; Kidney Transplantation; Pneumonia, Pneumocystis; Postoperative Complications; Prognosis; Sulfamethoxazole; Toxoplasmosis; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination; Virus Diseases

For immunocompromised patients virus infections represent a definite risk, particularly infections with measles virus and viruses of the herpes group (primary infections or reactivations). Vidarabine, acyclovir and bromovinyldeoxyuridine are therapeutically active against varicella, zoster, and herpes simplex, provided they are administered early in the course of disease. For zoster at least, the efficacy of interferon has been documented in controlled studies. No convincing therapy is so far available for the severe cytomegalovirus infections. Interferons obtained with DNA recombinant techniques are of significant promise in the near future.

Topics: Acyclovir; Antiviral Agents; Bromodeoxyuridine; Chickenpox; Cytomegalovirus Infections; Herpes Simplex; Herpes Zoster; Humans; Immune System Diseases; Vidarabine; Virus Diseases

Topics: Acyclovir; Antiviral Agents; Drug Resistance, Microbial; Female; Herpes Simplex; Humans; Mutation; Premedication; Simplexvirus; Thymidine Kinase; Virus Diseases; Viruses

Topics: Acyclovir; Humans; Virus Diseases

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; Humans; Infusions, Parenteral; Male; Retinitis; Virus Diseases

Topics: Acute Kidney Injury; Acyclovir; Adult; Female; Herpes Simplex; Herpes Zoster; Humans; Immunosuppressive Agents; Leukemia, Myeloid, Acute; Male; Neoplasms; Pregnancy; Pregnancy Complications; Virus Diseases

Topics: Acyclovir; Antifungal Agents; Antiviral Agents; Candidiasis; Dermatomycoses; Herpesviridae Infections; Humans; Imidazoles; Mycoses; Virus Diseases

In tissue culture, herpes simplex readily acquires resistance to nucleoside analogue inhibitors such as acyclovir. The two possible sites where resistance may develop are in the thymidine kinase (TK) and in the DNA polymerase genes; the commonest in vitro mutant is TK negative (TK-), although some strains may induce low levels of enzyme activity. The characteristics and modes of selection of these mutants are discussed, together with a preliminary consideration of the possible situation in man when antiviral drugs come to be more widely used.

Topics: Acyclovir; Drug Resistance, Microbial; Mutation; Simplexvirus; Thymidine Kinase; Virus Diseases

Topics: Acyclovir; Herpes Simplex; Herpes Zoster; Humans; Mouth Diseases; Stomatitis, Herpetic; Virus Diseases; Warts

Topics: Acyclovir; Antiviral Agents; Bromodeoxycytidine; Deoxycytidine; Deoxyuracil Nucleotides; Eye Diseases; Humans; Idoxuridine; Ophthalmic Solutions; Trifluridine; Vidarabine; Virus Diseases

Topics: Acyclovir; Animals; Antiviral Agents; Creutzfeldt-Jakob Syndrome; Demyelinating Diseases; Encephalitis; Encephalomyelitis; Guanine; Herpes Simplex; Humans; Nervous System Diseases; Polyradiculoneuropathy; Reye Syndrome; Vidarabine; Virus Diseases

Topics: Acyclovir; Amantadine; Amides; Antiviral Agents; Guanidine; Guanidines; Guanine; Interferons; Methisazone; Phosphonoacetic Acid; Pyrazoles; Pyrimidines; Ribonucleosides; Ribose; Thymidine; Vidarabine; Virus Diseases

Infectious viral diseases are an important worldwide problem and as a result of more efficient epidemiological studies and improved techniques of viral diagnosis "new" diseases are periodically identified. More importantly, as we learn to control cancer and perform tissue and organ transplants, the immunosuppressed patient is at greater risk of viral infection. There are currently very few generally accepted antiviral agents, but recent research efforts are encouraging. The status of the approved agents and of those showing the greatest promise is discussed in this article.

Topics: Acyclovir; Amantadine; Antiviral Agents; Evaluation Studies as Topic; Guanine; Humans; Interferons; Ointments; Ribavirin; Vidarabine; Virus Diseases; World Health Organization