acyclovir and Brain-Diseases

Viral encephalitis causes an altered level of consciousness, which may be associated with fever, seizures, focal deficits, CSF pleocytosis, and abnormal neuroimaging. Potential pathogens include HSV, VZV, enterovirus, and in some regions, arboviruses. Autoimmune (eg, anti-NMDA receptor) and paraneoplastic encephalitis are responsible for some cases where no pathogen is identified. Indications for ICU admission include coma, status epilepticus and respiratory failure. Timely initiation of anti-viral therapy is crucial while relevant molecular and serological test results are being performed. Supportive care should be directed at the prevention and treatment of cerebral edema and other physiological derangements which may contribute to secondary neurological injury.

Topics: Acyclovir; Adrenal Cortex Hormones; Anticonvulsants; Antiviral Agents; Brain Diseases; Brain Edema; Consciousness Disorders; Encephalitis; Encephalitis, Viral; Encephalomyelitis, Acute Disseminated; Glasgow Coma Scale; Guillain-Barre Syndrome; Hashimoto Disease; Humans; Intensive Care Units; Paraneoplastic Syndromes, Nervous System; Seizures; Status Epilepticus; Viremia

Encephalitis and postinfectious encephalitis represent two important conditions for the neurologist, both in terms of their presentations as neurologic emergencies and their potential to cause death or serious neurologic impairment. This article reviews the major infectious and noninfectious causes of encephalitis and discusses postinfectious encephalitis as an indirect effect of systemic illness.. Encephalitis caused by herpes simplex virus type 1 and West Nile virus are of major importance. In addition, within the past few years we have gained improved understanding of the neurologic syndromes caused by varicella-zoster virus, the recognition of enterovirus 71 as a significant human pathogen, and the realization that encephalitis may also occur by autoimmune mechanisms requiring immunosuppressive therapy. We have also learned that postinfectious encephalitis may be recurrent rather than monophasic, and that children and adults initially diagnosed with postinfectious encephalitis may later develop classic multiple sclerosis.. Encephalitis and postinfectious encephalitis present as neurologic emergencies requiring prompt diagnosis and initiation of treatment. Important concerns are to identify infectious conditions requiring antibiotic or antiviral therapy and postinfectious or other autoimmune encephalitides requiring immunosuppression.

Topics: Acyclovir; Adolescent; Antiviral Agents; Brain Diseases; Encephalitis; Encephalitis, Herpes Simplex; Encephalitis, Varicella Zoster; Encephalitis, Viral; Enterovirus Infections; Fatal Outcome; Female; Hashimoto Disease; Humans; Leukoencephalitis, Acute Hemorrhagic; Magnetic Resonance Imaging; Male; Middle Aged; West Nile Fever; Young Adult

A 31-year-old man was transferred to our emergency room (ER) with acute onset of high-grade fever and consciousness disturbance. His consciousness at ER was severely disturbed with restlessness. No apparent focal neurological signs were seen. MRI with diffusion-weighted images (DWI) showed high signal intensities at the corpus callosum, left cerebellar hemisphere, left deep white matter and right middle cerebellar peduncle. These lesions were low signals in apparent diffusion coefficient(ADC) map, indicating cytotoxic edema. EEG showed enhanced fast waves seen in predominantly frontal regions. CSF examination was normal except elevated initial pressure of 210 mmH2O. He was treated with high dose dexamethasone and acyclovir. His consciousness and high-grade fever with systemic inflammatory responses were dramatically improved after these treatments. Subsequent data showed hyperthyroidism with anti-thyroid stimulating hormone receptor antibodies. This case was thought to be a thyrotoxic encephalopathy with beneficial response to corticosteroid therapy. Abnormalities seen in DWI and EEG were normalized ten days later.

Topics: Acyclovir; Adult; Brain Diseases; Corpus Callosum; Dexamethasone; Diffusion Magnetic Resonance Imaging; Drug Therapy, Combination; Electroencephalography; Humans; Male; Thyrotoxicosis

A previously healthy 30-year-old woman was admitted to our hospital because of impaired consciousness after convulsion. A temporary diagnosis of herpes simplex encephalitis was made, and intravenous acyclovir (ACV) therapy (250 mg four times daily in normal saline over 2 hours) was started. Three days later, she became confused, and was having hallucinations, dysarthria and generalized painful seizures occurred without focal neurologic deficit. Whether the neuropsychiatric symptoms were related to herpes simplex encephalitis or acyclovir neurotoxity was initially unclear. The brain MRI and lumbar puncture findings were initially normal, but abnormal FLAIR lesions appeared later. ACV-associated encephalopathy was considered. ACV was discontinued, and she recovered from the neurological disorder within 24 hours. Although blood levels of acyclovir were not determined, it is unlikely that they were in a toxic range, in view of her normal renal function.

Topics: Acute Disease; Acyclovir; Adult; Antiviral Agents; Brain Diseases; Dysarthria; Encephalitis, Viral; Epilepsy, Generalized; Female; Hallucinations; Humans; Kidney Diseases; Magnetic Resonance Imaging

To define the clinical characteristics of acyclovir neurotoxicity and to outline how to distinguish it from viral encephalitis.. Case series of acyclovir neurotoxicity.. All cases reported in Index Medicus or in bibliographic reviews of acyclovir neurotoxicity plus two representative studies of Varicella zoster and Herpes simplex virus encephalitis.. Thirty-five patients who developed neuropsychiatric symptoms during acyclovir therapy.. Analysis of the patients' demographics, risk factors, acyclovir dosages and duration, clinical and laboratory findings and outcome.. All clinical and laboratory findings that were statistically significantly different from viral encephalitis.. The median age was 53.3 years. The most common predisposing factors were the use of other potentially neurotoxic medications (17 cases) and acute or chronic renal failure (15 cases). Acyclovir levels were frequently found above the therapeutic range. The characteristic manifestations were confusion (15 cases), hallucination or delirium (9 cases), agitation (8 cases) and lethargy (10 cases). Few patients had associated tremors (11 cases). Fever, headache, seizures and focal neurologic findings were distinctly rare. Cerebrospinal fluid and computed tomography were normal except in patients with other central nervous system disorders. Symptoms appeared within 2 days of therapy in the majority and resolved completely within several days of discontinuing acyclovir.. Acyclovir neurotoxicity is a self-limiting, dose-dependent phenomenon which is more common in the elderly, in patients with renal failure or in association with other neurotoxic medications. It is distinguished from viral encephalitis by its sudden onset, absence of fever or headache, lack of focal neurologic findings and normal cerebrospinal fluid.

Topics: Acyclovir; Aged; Brain Diseases; Diagnosis, Differential; Encephalomyelitis; Female; Humans

Although acyclovir is a key drug for the treatment of herpes infections, a consciousness disorder known as "acyclovir encephalopathy" is among its side effects. We encountered a patient with encephalopathy and measured the plasma and cerebrospinal fluid concentrations of acyclovir and its toxicologically active metabolite 9-carboxymethoxymethylguanine (CMMG). Before dialysis, cerebrospinal fluid concentrations of acyclovir and CMMG in this patient with a consciousness disorder were approximately 10% and 1%, respectively, of their plasma concentrations. After 3 days of dialysis, plasma CMMG levels decreased to detectable but below quantitative levels (<0.1 μg/mL), resulting in normal consciousness. These results suggest that decreasing plasma CMMG concentration could be one of clinical biomarkers for improving consciousness in patients with encephalopathy associated with acyclovir.

Topics: Acyclovir; Antiviral Agents; Brain Diseases; Consciousness Disorders; Humans; Renal Dialysis

To describe the clinical characteristics of anti-NMDAR encephalitis secondary to acute necrotizing encephalopathy caused by herpes simplex virus encephalitis in infants, and aid in its early recognition, diagnosis and treatment.. A total of 4 infants were included; all presented with fever, seizures, and progressive disturbances of consciousness and were diagnosed with herpes simplex virus (HSV-1) encephalitis. Cerebrospinal fluid (CSF) protein levels progressively increased, and the head MRI showed necrotizing encephalopathy. There was no significant improvement or recurrence after treatment with acyclovir, dexamethasone, or immunoglobulins. CSF reexamination at 3 weeks to 3 months showed positive anti-NMDAR IgG antibodies and gradual improvement after high-dose methylprednisolone therapy.. Infants with ANE associated with HSV can develop secondary anti-NMDAR encephalitis, recognition of which is critical to ensure the appropriate institution of immunotherapy after active CNS infection has been ruled out.

Topics: Acyclovir; Anti-N-Methyl-D-Aspartate Receptor Encephalitis; Brain Diseases; Encephalitis, Herpes Simplex; Herpes Simplex; Humans; Infant

Topics: Acyclovir; Aged, 80 and over; Antiviral Agents; Brain Diseases; Herpes Zoster; Humans; Male

We report a haemodialysis patient with end-stage renal failure whom a pharmacist aided in the management of acyclovir (ACV) encephalopathy, which may have been related to valacyclovir hydrochloride (VACV) administered without sufficient dose reduction. The patient 78 years was admitted with a tentative diagnosis of varicella zoster viral meningitis. A pharmacist suspected ACV encephalopathy related to excessive VACV administration and raised a query with the attending physician. According to the pharmacist's proposal, ACV administration was discontinued and continuous hemodiafiltration (CHDF) was performed. On day 5 of hospitalisation, the consciousness disorder was improved. In this report, we showed the detailed CHDF conditions of the present case, and the contribution of a pharmacist to treating and avoiding ACV encephalopathy was discussed.

Topics: Acyclovir; Brain Diseases; Drug-Related Side Effects and Adverse Reactions; Humans; Pharmacists; Valacyclovir

Topics: Acyclovir; Anti-Bacterial Agents; Antiviral Agents; Brain Diseases; Cefotaxime; Corpus Callosum; Diagnosis, Differential; Encephalitis; Humans; Influenza, Human; Male; Middle Aged

We report a case of acyclovir encephalopathy in a 77-year-old man who was introduced to peritoneal dialysis three years earlier. He developed herpes zoster and was treated with acyclovir (ACV) at 800 mg daily per oral. Two days later, he developed consciousness disturbance, hallucinations and asterixis. Acyclovir was stopped and continuous ambulatory peritoneal dialysis (CAPD) was switched to hemodialysis, which resulted in the resolution of his symptoms. Because the optimal dose of ACV varies among individuals depending on the bioavailability of ACV and metabolic enzyme activity, ACV encephalopathy can occur even when the acyclovir dose is modified according to the renal function of the affected patient. Because CAPD provides a poorer ACV clearance than hemodialysis, CAPD patients tend to have a higher risk of developing ACV encephalopathy and to recover more slowly. If CAPD patients develop ACV encephalopathy, a temporary change in the type of dialysis to hemodialysis should be considered.

Topics: Acyclovir; Administration, Oral; Aged; Antiviral Agents; Brain Diseases; Herpes Zoster; Humans; Male; Peritoneal Dialysis; Renal Dialysis

Herpes zoster (zoster) also commonly known as "shingles," occurs following re-activation of the varicella zoster virus. It contributes a large cost burden to the U.S. health care system, with an estimated 1 million cases costing $1 billion annually. The current gold standard treatment is acyclovir, which limits viral replication. However, acyclovir has been reported to cause neurotoxicity in patients with acute or chronic kidney disease.. This case presents an occurrence of acyclovir-induced toxic encephalopathy in a patient with normal renal function. A 63-year-old male presented to the emergency department with ataxia, tremors, fluctuating aphasia, confusion, agitation, and fatigue. Results of imaging, lumbar puncture, and laboratory studies directed clinicians toward acyclovir toxicity, despite a normal creatinine level. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Emergency physicians will likely be the first point of contact in the health care system following the onset of acyclovir toxicity. With an increasing incidence of zoster disease, such atypical toxic manifestations may increase. Early recognition is important to avoid permanent neurologic compromise.

Topics: Acyclovir; Antiviral Agents; Brain Diseases; Ceftriaxone; Emergency Service, Hospital; Exanthema; Herpes Zoster; Herpesvirus 3, Human; Humans; Male; Middle Aged; Neurotoxicity Syndromes

Topics: Acyclovir; Aged; Antiviral Agents; Brain Diseases; Herpes Zoster; Humans; Kidney Failure, Chronic; Male; Renal Dialysis

An 81-year-old woman suffering from sarcoidosis, chronic renal failure caused by hypertention was treated by valacyclovir 500 mg/day, for the diagnosis of herpes zoster of her right back. Her consciousness gradually became worse, and 3 days after taking the drug, she was sent to the emergency department of the hospital. Her conscious level was E2V2M5 (Glasgow Coma Scale) and myoclonus especially in her lower extremities occurred. Head CT and MRI show no obvious, acute abnormal findings other than chronic ischemic lesions, while an electroencephalogram (EEG) shows periodic synchronous discharges (PSDs) and disorganized background activity. Based on these findings, she was diagnosed as valacyclovir-associated acute encephalopathy. After conservative therapy of maintenance hemodialysis, her consciousness gradually improved, and PSDs disappeared accordingly and background activity of EEG became improved. In this case report, we presented valacyclovir-associated neurotoxicity with PSDs in EEG as potentially a surrogate marker. We should be cautious to use valaciclovir which may cause drug-induced encephalopathy especially in elderly or patients with renal failure even though the dose was adjusted in advance.

Topics: Acute Disease; Acyclovir; Aged, 80 and over; Antiviral Agents; Brain Diseases; Electroencephalography; Female; Herpes Zoster; Humans; Kidney Failure, Chronic; Periodicity; Valacyclovir; Valine

Topics: Acyclovir; Adult; Antiviral Agents; Brain Diseases; Central Nervous System Diseases; Cerebral Arterial Diseases; Chickenpox; Fatal Outcome; Fever; Glomerulonephritis; Herpesvirus 3, Human; Humans; Kidney Transplantation; Magnetic Resonance Imaging; Male

Post-malaria neurological syndrome (PMNS) defined by a post-infective encephalopathy occurring within 2 months after an episode of Plasmodium falciparum infection is still a debated entity. We describe 2 cases of PMNS in 2 patients of African origin, born and living in France. Both patients had severe P. falciparum infection, followed by PMNS. They recovered with no sequelae. These are the first-reported cases of PMNS in patients of African ethnicity and living in France.

Topics: Acyclovir; Adolescent; Adult; Brain Diseases; Cote d'Ivoire; Encephalitis, Herpes Simplex; France; Gambia; Humans; Malaria, Falciparum; Male; Syndrome; Treatment Outcome

Two previously healthy girls presented acute encephalopathy due to varicella, with severe alteration of the conscious level and seizures. Both patients improved progressively after 15 days, with complete clinical recovery.

Topics: Acyclovir; Brain Diseases; Chickenpox; Child, Preschool; Female; Humans; Immunocompromised Host; Spain

Acyclovir-induced neurotoxicity is a rare adverse effect, found especially in adults with pre-existing renal failure. We report a case of neurotoxicity of acyclovir in a six-month-old liver transplant recipient. Case report and review of literature are discussed.

Topics: Acyclovir; Antiviral Agents; Brain Diseases; Female; Humans; Infant; Liver Transplantation

Infants with neonatal herpes, classified as central nervous system or disseminated disease, have a high incidence of moderate and severe neurologic deficits despite standard acute therapy.. Following completion of parenteral therapy, infants with central nervous system and/or disseminated disease received 2 years of continuous oral acyclovir therapy. Target minimum peak serum acyclovir concentrations were >2 microg/ml for the first three patients, and >3 microg/ml for the subsequent 13 patients. Safety assessments were made every 3 months. We evaluated neurodevelopmental outcomes with Bayley Scales of Infant Development.. A total of 16 consecutive herpes simplex virus-infected infants born during 1990 to 2003 received the treatment plan; 13/16 infants had central nervous system disease; 3 had disseminated disease without central nervous system involvement. A total of 69% (11/16) had Bayley scores in the normal range for mental development and 79% (11/14) had motor scores in the normal range. At the final assessment, five children had developmental delays. One child had severe mental delay with normal motor development. Four children had mild mental delays, with severe motor delays in three. All children were independently mobile, without seizure disorder, had normal vision, and had speech development. During the 2-year course of treatment, five children had brief recurrences of dermal lesions, and none had evidence of neurologic deterioration. There were no serious or sustained adverse drug reactions.. This pilot study reports improved outcomes in a small cohort of infants with a prolonged course of oral acyclovir. A minority of these children exhibited mild or significant developmental delays. Further investigation of this approach to treatment is warranted.

Topics: Acyclovir; Administration, Oral; Brain; Brain Diseases; Child Development; Child, Preschool; Developmental Disabilities; Herpes Simplex; Humans; Infant; Infant, Newborn; Pilot Projects; Treatment Outcome

Topics: Acyclovir; Antiviral Agents; Brain Diseases; Female; Herpes Zoster; Humans; Kidney Failure, Chronic; Middle Aged

Topics: Acyclovir; Administration, Oral; Antiviral Agents; Brain Diseases; Confusion; Humans; Male; Middle Aged

We report the case of a 65-year-old man treated with intravenous acyclovir and amoxicilline for meningoencephalitis. Six days later, he suddenly developed acute renal failure, associated with central nervous system symptoms. The high acyclovir concentration in plasma and spinal fluid confirmed the hypothesis of acyclovir toxicity. Continuous haemofiltration resulted in a rapid amendment of neurologic and renal symptoms. Despite the high therapeutic index of acyclovir, manifestations of neurotoxicity and nephrotoxicity are not a rare event. The risk is increased in the elderly and in patients with renal insufficiency. Rapid intravenous injections are contraindicated. Continuous haemofiltration is rapidly efficient. The value of acyclovir concentration determination in plasma and spinal fluid are stressed.

Topics: Acute Kidney Injury; Acyclovir; Aged; Antiviral Agents; Brain Diseases; Humans; Male; Meningoencephalitis

To investigate the ocular complications of herpes zoster ophthalmicus in patients with human immunodeficiency virus (HIV) infection.. This was a retrospective cohort study of 48 HIV-infected patients (48 eyes) treated at San Francisco General Hospital for herpes zoster ophthalmicus from December 1985 through March 1994.. All patients were initially treated with either intravenous or oral acyclovir. The median CD4 lymphocyte count at diagnosis was 48 per mm3 (range, 2 to 490 per mm3). Fifteen patients (31%) had mild or no ocular involvement. Seventeen patients (35%) had stromal keratitis, mostly mild, and two (4)% developed chronic infectious pseudodendritic keratitis. Twenty-four study patients (50%) had iritis, but only three (6%) had elevations in intraocular pressure. Two patients (4%) developed postherpetic neuralgia, and two others (4%) had zoster-associated central nervous system disease. Only two patients (4%) developed necrotizing retinitis, both in the form of the progressive outer retinal necrosis syndrome.. Excluding the patients with retinitis and central nervous system disease, the rate of sight-threatening complications in our series was lower than expected. Almost one third of study patients had no ocular complications or only mild surface epithelial disease. Although the relatively low incidence of sight-threatening disease in our study population may have been a consequence of aggressive management with acyclovir, chronic infectious pseudodendritic keratitis, retinitis, and central nervous system disease, complications of ophthalmic zoster whose pathogenesis is largely a consequence of active viral replication, were particularly devastating and difficult to manage.

Topics: Acyclovir; Adult; Antiviral Agents; Brain Diseases; CD4 Lymphocyte Count; CD4-Positive T-Lymphocytes; Cohort Studies; Eye Diseases; Female; Herpes Zoster Ophthalmicus; HIV Infections; Humans; Iritis; Keratitis; Male; Middle Aged; Neuralgia; Retinal Necrosis Syndrome, Acute; Retrospective Studies

Topics: Acyclovir; Aged; Brain Diseases; Female; Humans; Kidney Diseases; Renal Insufficiency

Topics: Acyclovir; Adult; Antiviral Agents; Brain Diseases; Herpes Zoster; Humans; Kidney Failure, Chronic; Male; Renal Dialysis; Skin Diseases, Viral

Topics: Acyclovir; Adult; Brain Diseases; Diagnosis, Differential; Herpes Zoster; Humans; Kidney Failure, Chronic; Male; Meningoencephalitis

Early antiviral treatment is important for herpes simplex encephalitis. A reliable test for supporting empirical therapy with antiviral agents is urgently needed. Sixty-six children with fever, focal seizures, and consciousness disturbance had their sera examined for anti-herpes simplex viral immunoglobulin M (IgM) antibody with enzyme-linked immunosorbent assay. The result was positive in all seven patients confirmed to have herpes simplex encephalitis. Only two of the other 59 patients were positive on this test. The average period for the development of serologic positivity was 7.3 days from the onset of neurologic symptoms. Although most sera were not tested in the early stage, all were collected on admission day. Our data suggest that before further evidence indicates another diagnosis, this simple, but specific IgM antibody test could be used as a guide for deciding to continue the antiviral treatment for serologically positive cases or to discontinue antiviral treatment for serologically negative ones. Yet, we would not suggest diagnosing herpes simplex encephalitis with this test alone.

Topics: Acyclovir; Blood; Brain Diseases; Cerebrospinal Fluid; Electroencephalography; Female; Herpes Simplex; Humans; Immunoglobulin M; Infant; Injections, Intravenous; Male; Tomography, X-Ray Computed

Thymidine kinase (TK) of herpes simplex virus (HSV) has been identified as one of the factors responsible for its virulence. We have previously isolated acyclovir (ACV)-resistant HSV type 2 (HSV-2), strain YS-4 C-1, by simple plaque cloning from a clinical isolate. Although YS-4 C-1 had extremely low TK activity, it retained high virulence in mice. To determine the mechanism of the reduction of TK activity, a molecular analysis of the YS-4 C-1 TK gene was performed. YS-4 C-1 produced TK mRNA, which was indistinguishable both in size and amount from that of wild-type strains. However, the YS-4 C-1 TK had a single amino acid change from serine to asparagine at amino acid residue 182 of the TK polypeptide, which was caused by a single nucleotide mutation. It was situated within a highly conserved region (162-194) and close to the putative nucleoside-binding site (169-177), one of the three active centers of TK. In order to confirm the effect of this missense mutation on both the TK activity and neurovirulence, the mutation was introduced into the TK genes of wild-type strains. Although all the recombinants were altered to ACV-resistant viruses with reduced TK activity, they retained high neurovirulence for mice. Our study thus suggested that this mutant TK, in spite of low activity, might play a role in the neurovirulence of HSV-2.

Topics: Acyclovir; Adult; Animals; Base Sequence; Brain Diseases; Cloning, Molecular; DNA Mutational Analysis; DNA, Viral; Female; Genes, Viral; Humans; Infant; Mice; Mice, Inbred BALB C; Molecular Sequence Data; Restriction Mapping; Simplexvirus; Thymidine Kinase; Vero Cells; Virulence

We report a case of reversible myoclonic encephalopathy which appeared after intravenous acyclovir treatment in a patient in CAPD for which pharmacological dosages have been made in serum, peritoneal dialysate and cerebrospinal fluid (CSF). Encephalopathy appeared after two intravenous doses of 7.33 mg/kg (doses higher than recommended), administered on admission and 16 hours later. Pharmacological dosages indicated that acyclovir peritoneal clearance was negligible, and that acyclovir persisted a long time in plasma and CSF. Neurological symptoms persisted although serum concentrations returned to normal value. The diagnostic value of pharmacological dosages in serum and CSF is discussed. In addition, neurological symptoms disappeared following two consecutive hemodialysis procedures. Hence we suggest that hemodialysis could be used for drug removal in case of acyclovir overdose in CAPD patients.

Topics: Acyclovir; Brain Diseases; Humans; Middle Aged; Peritoneal Dialysis, Continuous Ambulatory

The phosphonylmethoxyalkyl derivative (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine (HPMPC) was evaluated for its in vivo efficacy in several model infections for herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) and thymidine kinase-deficient (TK-) HSV-1 in mice. In hairless mice infected intracutaneously with HSV-1 or HSV-2, HPMPC completely suppressed all manifestations of the disease (skin lesions, paralysis of the hind legs, and mortality) if it was administered topically at a concentration of as low as 0.1, 0.3, or 1%. Similarly, HPMPC completely suppressed TK- HSV-1 infection in athymic nude mice if it was administered topically at 0.1 or 0.3% or intraperitoneally at 100 or 250 mg/kg/day. HPMPC was also effective against intraperitoneal HSV infection if it was given orally at a dose of 50 mg/kg/day or higher. In mice inoculated intracerebrally with HSV-2, intraperitoneal HPMPC treatment achieved a significant and dose-dependent protection at doses ranging from 5 to 400 mg/kg/day. The protective effect of HPMPC (at 200 mg/kg/day) was accompanied by a complete inhibition of virus multiplication in the brain. In all models of infections studied, the efficacy of HPMPC proved to be superior to that of acyclovir. The most remarkable feature of HPMPC was that a single administration of the compound, even as late as 4 days after infection, conferred significant protection against HSV-1 or HSV-2 infection. Topical or systemic HPMPC treatment is efficacious in murine models of HSV-1, HSV-2, and TK- HSV infections.

Topics: Acyclovir; Animals; Antiviral Agents; Brain Diseases; Cidofovir; Cytosine; Herpes Simplex; Mice; Mice, Hairless; Mice, Nude; Organophosphonates; Organophosphorus Compounds; Peritoneal Cavity; Skin Diseases, Infectious

We have treated 113 patients with zidovudine since its licensure, 80 with acquired immunodeficiency syndrome and 33 with acquired immunodeficiency syndrome-related complex. This paper reports on the efficacy and toxicity observed in these patients. Improved well-being, reduced frequency and severity of opportunist infections were notable in the first year of follow-up. More rapid improvement in pulmonary physiological tests during recovery from Pneumocystis carinii pneumonia was also observed in treated patients. Patients with lower initial platelet counts showed early increases in platelet counts. There was a consistent fall in human immunodeficiency virus (HIV) p24 antigen during treatment, although not always to undetectable levels. CD4 cell counts showed a rise in the first months of treatment but these were not sustained, despite continuing clinical benefit. Neuropsychological and clinical evidence of benefit in HIV encephalopathy are described. We have analysed the factors influencing marrow toxicity and have found that low CD4 count and the intercurrent use of ganciclovir and dapsone increase myelotoxicity. We describe the clinical and biochemical features of the myopathy associated with long-term use of zidovudine and summarise our findings on dose-reduction associated meningo-encephalitis.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; AIDS-Related Complex; Bone Marrow; Brain Diseases; Dapsone; Ganciclovir; HIV Antigens; HIV Core Protein p24; Humans; Meningoencephalitis; Muscular Diseases; Neuropsychological Tests; Opportunistic Infections; Respiratory Function Tests; Retroviridae Proteins; T-Lymphocytes; T-Lymphocytes, Helper-Inducer; Zidovudine

9-(1,3-Dihydroxy-2-propoxymethyl)guanine (DHPG), was evaluated in cell culture and in animals for its inhibitory effect on herpes simplex viruses. Compounds run for comparison included acyclovir, 2'-fluoro-2'-deoxy-5-iodo-arabinofuranosylcytosine (FIAC), and 2'-fluoro-2'-deoxy-5-methyl-arabinofuranosyluracil (FMAU). In plaque reduction assays DHPG, acyclovir, FIAC, and FMAU were inhibitory to six herpes types 1 and 2 virus strains at concentrations of 0.2-2.4 microM. These concentrations were much lower than those required to inhibit Vero cell proliferation. In guinea pig vaginal infections, DHPG provided significantly greater inhibition of herpetic lesions than did acyclovir. In a herpes type 2 infection model in mice, DHPG, and FMAU were active at 5 mg/kg, whereas acyclovir and FIAC showed no statistically significant effect at 80 mg/kg. In a herpes type 1 encephalitis model, DHPG and FMAU were active at doses less than 10 mg/kg, with FMAU being about 4 times more potent than DHPG in that model.

Topics: Acyclovir; Animals; Antiviral Agents; Arabinofuranosyluracil; Brain Diseases; Cell Line; Chlorocebus aethiops; Cytarabine; Encephalitis; Female; Ganciclovir; Guinea Pigs; Herpes Genitalis; Herpes Simplex; Kidney; Mice; Simplexvirus; Structure-Activity Relationship

The development of antiviral therapy for neonatal herpes simplex virus infection has lead to a significant decrease in mortality and improved morbidity. Vidarabine administered at dosages of either 15 mg/kg or 30 mg/kg for ten days leads to 60% overall survival in babies with either central nervous system, CNS, or disseminated disease (n = 59). Babies with CNS disease had a survival rate of 88% compared to those with disseminated disease where survival was only 35%. The introduction of acyclovir into clinical trials has provided the opportunity to further study this disease using a drug with a higher in vitro therapeutic index. While efficacy analyses have not been performed for this ongoing, comparative study, 90% of babies with CNS infection (n = 45) survive as do 65% with disseminated infection (n = 29). Babies with skin, eye, and mouth involvement do well regardless of therapeutic modality. Factors influencing improved treatment are discussed.

Topics: Acyclovir; Antibodies, Viral; Brain Diseases; Female; Herpes Simplex; Humans; Infant, Newborn; Pregnancy; Pregnancy Complications, Infectious; Vidarabine

A case of fulminant hepatic failure, associated with infectious mononucleosis, in a previously healthy 14-year-old girl is reported. Despite intensive therapy, which included the use of acyclovir, charcoal haemoperfusion, and measures to control her raised intracranial pressure (guided by serial EEG and auditory brainstem-evoked response recordings), the outcome was fatal.

Topics: Acyclovir; Adolescent; Brain Diseases; Charcoal; Female; Hemoperfusion; Humans; Infectious Mononucleosis; Kidney Diseases