Acyclovir
brand name: Zovirax

Acyclovir is a viral medication used to treat herpes genitalis, herpes simplex, and herpes zoster, as well as in some cases chickenpox. Acyclovir does not in fact cure the herpes infection; it decreases the symptoms and its appearance, as well as the annoying itching. In this way it helps anti-infection drugs to heal it faster. It can be administered orally or applied topically, though the latter is preferred because it has fewer side effects. Oral administration can cause nausea, headaches, fatigue, diarrhea and sore throat in the short term and insomnia, depression, menstrual complications and acne in the long term. A very important benefit of acyclovir is that it seems to prevent any future outbreaks of herpes, the incidence of which is high. It is sold under the brand names Acyclostad™ and Zovirax™.

Int J Pediatr Otorhinolaryngol. 2005 Apr 30;
Comparisons of steroid, acyclovir, lipoprostoglandin E1 and steroid+acyclovir treatments in facial paralysis: A rat study.
Gok U, Alpay HC, Akpolat N, Yoldas T, Kilic A, Yilmaz B, Kabakus N.
Firat University, Medical Faculty, Otorhinolaryngology Department, Elazig, Turkey.

OBJECTIVE:: To induce experimental peripheral facial paralysis by inoculation of HSV1 and to compare the effects of steroid, acyclovir, lipoprostoglandin E2 and steroid+acyclovir treatments in terms of clinical recovery, electrophysiologically and histopathologically. MATERIALS AND METHODS:: A total of 132 adult female rats were used in this study. HSV type 1 strain was inoculated at the back of the left ear by using 27 gauge needle. Of all animals, 70 (53%) rats which developed facial paralysis were divided into five groups (n=14 for each group) as control, steroid+acyclovir, lipoprostaglandin E1, steroid only and acyclovir only. At the end of the 21 days period, the rats were clinically examined and electrophysiological tests were performed, then decapitated and the nerve specimens were obtained. RESULTS:: A modified electroneurography (ENoG) test was performed and the latencies and the amplitudes were compared. The findings of the intact side were better, but with no significant difference. Histopathologicaly edema was significantly smaller in all groups compared to the controls (p<0.05). Similarly, no difference was seen in terms of vacuolar degeneration and Schwann cell hyperchromatisation among the groups and no significant difference in recovery period and rate of facial paralysis when all groups were compared. CONCLUSION:: Facial paralysis induced by HSV1 recovered spontaneously within a week. In the treatment of facial paralysis, steroid alone, acyclovir alone, steroid+acyclovir, or lipoprostaglandin E1 all reduced edema in the infected facial nerve but there was no statistical difference in of the rate or degree of recovery.

Skinmed. 2005 May-Jun;4(3):186-7.
Case study: inoculation herpes barbae.
Parlette EC, Polo JM.
Naval Hospital, Okinawa, Japan ecparlette@hotmail.com.

A 21-year-old white man in otherwise excellent general health was referred for a painful, progressive, facial eruption with associated fever, malaise, and cervicofacial lymphadenopathy. The patient reported that a vesicular eruption progressed from the left side of his face to also involve the right side of his face over the 48 hours preceding his clinic visit. He also reported some lesions in his throat and the back of his mouth causing pain and difficulty swallowing. Four to 7 days before presentation to us, the patient noted exposure to his girlfriend's cold sore. Additionally, he complained of a personal history of cold sores, but had no recent outbreaks. Physical examination revealed a somewhat ill man with numerous vesicles and donut-shaped, 2-4 mm, crusted erosions predominantly on the left side of the bearded facial skin. There were fewer, but similar-appearing lesions, on the right-bearded skin. The lesions appeared folliculocentric (Figure). Cervical and submandibular lymphadenopathy was present. Oral exam showed shallow erosions on the tonsillar pillars and soft palate. Genital examination was normal. The remainder of the physical exam was unremarkable. A Tzanck smear of vesicular lesions was positive for balloon cells and many multinucleated giant cells with nuclear molding. A viral culture was performed which, in several days, came back positive for herpes simplex virus. The complete blood cell count documented a white blood cell count of 8000/mm3 with 82.6% neutrophils and 9.0% lymphocytes. Based on the clinical presentation and the positive Tzanck smear, the patient was diagnosed with herpes simplex barbae, most likely spread by shaving. The patient was started on acyclovir 200 mg p.o. five times daily for 10 days. Oxycodone 5 mg in addition to acetaminophen 325 mg (Percocet; Endo Pharmaceuticals, Chadds Ford, PA) was prescribed for pain relief. A 1:1:1 suspension of viscous lidocaine (Xylocaine; AstraZeneca Pharmaceuticals LP, Wilmington, DE), diphenhydramine (Benadryl; Pfizer Inc., New York, NY), and attapulgite (Kaopectate; Pfizer Inc., New York, NY) was given as a swish and spit to relieve the oral discomfort. Good hygiene, no skin-to-skin contact with others, and no further shaving to prevent autoinoculation were stressed. He was advised to discard his old razor.

Primary cutaneous T- and B-cell lymphomas are a heterogeneous group of diseases with varied clinical presentations and prognosis. The use of new molecular, histological, and clinical criteria has improved their recognition. Cutaneous B-cell and T-cell lymphomas are seldom found together in the same patient. Here we report a rare case of mycosis fungoides variant of a cutaneous T-cell lymphoma (CTCL) which later developed Epstein-Barr virus (EBV) associated cutaneous B-cell lymphoproliferative disorder. The patient initially presented with generalized erythroderma, extensive plaques, and axillary lymphadenopathy. Histopathology and immunophenotyping of her tumor from the right breast nodule revealed a T-cell lymphoma consistent with mycosis fungoides. She was initially treated with pentostatin, followed by topical mechlorethamine and topical steroids. After progression of her mycosis fungoides with worsening diffuse skin lesions on this regimen, her treatments were changed to oral bexarotene with an initial partial response followed by stable disease. Three years from her initial presentation, she developed ulcerated cauliflower-like nodules on her forehead. Biopsy of these lesions revealed EBV-positive large- and medium-sized pleomorphic B-cells consistent with EBV-driven B-cell lymphoproliferative disorder. She was treated with topical acyclovir cream on the involved skin areas while continuing with oral bexarotene for mycosis fungoides. Skin lesions gradually diminished and totally disappeared after four weeks of topical acyclovir treatment. Bexarotene treatment was continued for another year until the mycosis fungoides progressed and became wide spread causing her death four and a half years after the initial diagnosis. The coexistence of two cutaneous non-Hodgkin lymphomas of different lineage in the same patient and the complete clinical response of EBV-related B-cell cutaneous component to topical acyclovir makes this rare case particularly interesting.

Semin Pediatr Infect Dis. 2005 Jan;16(1):7-16.
Neonatal herpes: What have we learned.
Kimberlin DW, Whitley RJ.

Neonatal herpes simplex virus (HSV) infection usually is acquired during the birth process, as the neonate comes in contact with the virus during passage through an infected birth canal. After an incubation period which can last as long as 2 to 4 weeks, neonatal HSV disease then manifests in 1 of 3 ways: (1) disseminated disease, with visceral organ involvement (including infection of the brain in two-thirds to three-quarters of patients); (2) central nervous system disease (with no other visceral organ involvement, but with skin lesions in two-thirds of patients); or (3) disease limited to the skin, eyes, and/or mouth (ie, SEM disease). Diagnostic advances in recent years have focused primarily on applying polymerase chain reaction technology to babies suspected of having neonatal HSV disease. Treatment of neonatal HSV disease with intravenous acyclovir has improved the likelihood of survival substantially, although neurologic morbidity remains a common sequelae, especially among survivors of central nervous system disease. Despite these advances, the duration of time from onset of symptoms and initiation of antiviral therapy has remained unchanged for the past 20 years. The surest way to improve outcomes rapidly at this point is to raise awareness of neonatal HSV disease, resulting in the establishment of earlier diagnoses and more rapid institution of antiviral therapy. In the longer term, development of a bedside nucleic acid detection kit for real-time detection of HSV DNA in the maternal genital tract at the time of delivery could identify which babies are at risk of developing neonatal HSV disease.

J Viral Hepat. 2005 Jan;12(1):2-9.
Treatment of hepatitis D.
Niro GA, Rosina F, Rizzetto M.
Division of Gastroenterology, Hospital 'Casa Sollievo Della Sofferenza', IRCCS, San Giovanni Rotondo (FG), Italy.

Summary. Delta virus related chronic hepatitis is difficult to treat. The response to alpha-interferon (IFN), which still represents the only therapy for chronic hepatitis D, varies widely and occurs at different times from the beginning of treatment. The rate of response is proportional to the dose of IFN, with 9 million units (MU) three times a week being more effective than 3 MU thrice weekly. Sustained responses are unusual and are accompanied by the clearance of serum hepatitis B virus surface antigen (HBsAg), seroconversion to anti-HBs and improvement of liver histology. Although disease of a short-standing may respond better to therapy, clear predictors of response are still unidentified. Besides IFN, other therapeutic approaches such as immunosuppressive drugs, acyclovir, ribavirin and thymosin, have been unhelpful. Available evidence does not support the use of deoxynucleotide analogues. Famciclovir has no effect on disease activity and hepatitis D virus (HDV)-RNA levels. Twelve- or 24-month lamivudine treatment does not significantly affect biochemical, virological or histological parameters. Pegylated-IFN could represent a reasonable therapeutic option in the long-term treatment required for chronic hepatitis D. Antisense oligonucleotides and prenylation inhibitors hold promise as therapeutic agents of the future. Liver transplantation provides a valid option for end-stage HDV liver disease; the risk of re-infection is lower for HDV than for HBV under long-term administration of hyperimmune serum against HBsAg. Molecularly tailored drugs capable of interfering with crucial viral replicative processes of HDV appear to be the best prospect in the treatment of hepatitis D.

J Neurol Sci. 2004 Jan 15;217(1):111-3.
Acyclovir responsive brain stem disease after the Ramsay Hunt syndrome.
Hu S, Walker M, Czartoski T, Cheng A, Forghani B, Gilden DH, Garden GA.
Department of Neurology, University of Washington, Box 356465, 98195, Seattle, WA, USA

We report an immunocompetent patient with the Ramsay Hunt syndrome (RHS) followed days later by brainstem disease. Extensive virological studies proved that varicella zoster virus (VZV) was the causative agent. Treatment with intravenous acyclovir resulted in prompt resolution of all neurological deficits except peripheral facial palsy. This case demonstrates that after geniculate zoster, brainstem disease may develop even in an immunocompetent individual and effective antiviral therapy can be curative.

J Med Virol. 2004 Jan;72(1):112-20.
Okuda T, Kurokawa M, Matsuo K, Honda M, Niimura M, Shiraki K.
Suppression of generation and replication of acyclovir-resistant herpes simplex virus by a sensitive virus.
Department of Virology, Toyama Medical and Pharmaceutical University, Toyama, Japan.

The role of acyclovir-sensitive herpes simplex virus (HSV) was analyzed in the process of its replacement by a resistant virus in vitro and in vivo in the aspect of acyclovir therapy. The mode of replacement of acyclovir-sensitive HSV with acyclovir-resistant HSV was examined by the passages of acyclovir-sensitive wild type HSV in Vero cells under acyclovir-treatment. The development of resistance was monitored more adequately by counting the number of acyclovir-resistant viruses in 10,000 plaque forming units than by the conventional susceptibility assay. The resistance increased with the proportion of thymidine kinase-deficient (TK(-)) viruses, when the susceptibilities of acyclovir-treated HSV population to 5'-iodo-2'deoxyuridine and phosphonoacetic acid were examined. The increased resistance was due to the increased proportion of acyclovir-resistant virus but not intermediately resistant virus. Infection with mixtures of TK(-) and acyclovir-sensitive strains rendered TK(-) sensitive to acyclovir, and virus yields were reduced to the levels of acyclovir-sensitive virus in Vero cells. Their yield reduction depended on the proportion of acyclovir-sensitive viruses and induction of TK activity. This reduction in virus yields of the mixture of TK(-) and acyclovir-sensitive strains was confirmed by acyclovir treatment in the skin of mice with cutaneous infection. Acyclovir treatment combined with superinfection of acyclovir-sensitive virus delayed the development of herpetic skin lesions due to acyclovir-resistant virus and reduced virus yields in the infected skin. Acyclovir-sensitive virus plays an important role in suppressing the generation and replication of acyclovir-resistant virus during acyclovir therapy.

Ann Pharmacother. 2003 Dec;37(12):1814-1817.
Possible Valacyclovir-Related Neurotoxicity and Aseptic Meningitis.
Olin JL, Gugliotta JL.
Jacqueline L Olin MS PharmD BCPS, Clinical Assistant Professor, Department of Pharmacy Practice and Administration, Ernest Mario School of Pharmacy at Rutgers, The State University of New Jersey, Piscataway, NJ; Clinical Coordinator, Department of Pharmacy, Hunterdon Medical Center, Flemington, NJ.

To report a case of neurotoxicity and aseptic meningitis in a patient receiving valacyclovir. An 86-year-old white man had started valacyclovir 1 g 3 times a day for a herpetic rash along the left side of his face. He subsequently presented with balance difficulties, constant frontal headaches, and a seizure 1 day prior to admission. Cerebral spinal fluid (CSF) analysis revealed 162 white cells/mm(3), 1 red blood cell/mm(3), glucose 56 mg/dL, and protein 144 mg/dL, with a negative Gram stain. Further laboratory examination failed to demonstrate other causes for the patient's clinical picture. After discontinuation of valacyclovir and supportive care, the patient symptomatically improved. As of the third week of September 2003, only 1 other case of valacyclovir-related aseptic meningitis was published describing a patient with characteristics similar to those of our patient. Our patient's neurologic symptoms may have been due to acyclovir toxicity, but acyclovir-toxic patients present with normal CSF findings. Several drug classes, including nonsteroidal antiinflammatory drugs, antibiotics, and intravenous immunoglobulins, can induce aseptic meningitis. Other reasons for the patient's symptoms or causes of meningitis were excluded, although viral meningitis remains a possibility. Valacyclovir-induced aseptic meningitis was considered to be possible according to the Naranjo probability scale. Healthcare providers should be aware of valacyclovir as a possible cause of drug-induced aseptic meningitis.

Eye. 2003 Nov;17(8):919-22.
Pathogenesis and management of herpes simplex virus keratitis.
Tullo A.
Department of Ophthalmology, Manchester Royal Eye Hospital, Manchester, UK.

Herpes simplex keratitis (HSK) remains a common cause of unilateral corneal disease. Despite intense research over three decades, the mainstay of therapy continues to be topical and, more recently, systemic acyclovir plus topical corticosteroid in some cases. There is increasing recognition that HSK after keratoplasty can occur not only as a result of recurrence in patients with HSK, but also in patients with other primary diagnoses as a result of activation of HSV in the host, or by transmission of virus in the donor tissue.

J Gastroenterol. 2003;38(10):1005-8.
Herpes simplex virus hepatitis 4 years after liver transplantation.
Bissig KD, Zimmermann A, Bernasch D, Furrer H, Dufour JF.
Division of Internal Medicine, Bern, Inselspital, Switzerland.

If not promptly recognized and treated, herpes simplex virus (HSV) hepatitis is associated with a high mortality. A patient transplanted for primary sclerosing cholangitis required, 4 years later, a colectomy for a steroid-resistant flare of ulcerative colitis. He subsequently developed fever, with genital and oral ulcerations. He was hospitalized for diabetic decompensation with massive elevation of serum aminotransferases. Examination revealed vesicles on the hands. Liver biopsy showed Cowdry type B inclusions. Therapy with acyclovir was immediately initiated and the patient recovered. This case illustrates the diagnostic importance of mucocutaneous lesions in the assessment of complications after liver transplantation.

Scand J Infect Dis. 2003;35(10):770-2.
A case of chronic renal dysfunction following treatment with oral acyclovir.
Sodhi PK, Ratan SK.
Department of Ophthalmology, Safdarjung Hospital, New Delhi, India.

Nephrotoxicity is a well-known side effect of intravenous acyclovir treatment but occurs rarely by oral treatment. A 76-y-old healthy male, with normal baseline renal functions (blood creatinine 0.6 mg%), received oral acyclovir at a dose of 800 mg five times daily for 10 days for treatment of herpes zoster ophthalmicus. He developed renal failure with blood creatinine levels of 3 mg% and his renal function failed to improve within eight months of end of treatment. Affection of renal function has to be considered also in relation to oral acyclovir treatment, especially in elderly subjects.