Summary
Synopsis: Acyclovir (aciclovir)1 is a nucleoside analogue antiviral drug related to cytarabine, idoxuridine, trifluridine and vidarabine. In common with these earlier antivirals, acyclovir is active against some members of the herpesvirus group of DNA viruses. The efficacy of topical acyclovir has been convincingly demonstrated in ocular herpetic keratitis, and in initial and primary initial genital herpes infection, but little or no clinical benefit was seen when non-primary initial genital infections were assessed separately. Acyclovir ointment demonstrated little benefit in recurrent genital herpes but topical acyclovir cream decreased the course of the infection by 1 to 2 days. Orally and intravenously administered acyclovir were beneficial in initial genital herpes infections, and oral therapy shortened the duration of recurrent infections by 1 to 2 days but did not ameliorate pain. In non-immunocompromised patients with recurrent herpes simplex labialis, generally little clinical benefit was seen with the use of topical acyclovir ointment even when therapy was initiated during the prodromal phase, while topical acyclovir cream effected small but significant improvements in the clinical but not the symptomological course of the disease. However, in immunocompromised patients, both intravenous and topical acyclovir shortened the clinical course of herpes simplex virus infections occurring mainly on the lips, oral mucosa and face, and prophylaxis with either oral or intravenous acyclovir suppressed the appearance of recurrent lesions from latent virus for the period of drug administration, but acyclovir did not eradicate latent herpesviruses.
In non-immunocompromised patients, intravenous acyclovir was shown to decrease the acute pain of zoster, especially in the elderly, but postherpetic neuralgia was not ameliorated. When immunocompromised patients were studied, intravenous acyclovir inhibited the progression of zoster infections and shortened the healing time and duration of viral shedding in patients with cutaneous disseminated zoster. However, acute and postherpetic pain were not significantly affected.
Well designed controlled studies are underway to establish the efficacy of acyclovir in herpes simplex encephalitis and cytomegalovirus infections in immunocompromised patients, infections due to Epstein-Barr virus, and neonatal herpesvirus infections.
Despite some aspects of the drug’s use which require further clarification, acyclovir will make a major impact on the treatment of herpesviral infections. Barring unexpected findings with wider clinical use, it will become the agent of choice in several conditions.
Antiviral Activity: Acyclovir is active in vitro against herpes simplex virus types 1 and 2, varicella zoster virus, Epstein-Barr virus and, to a very limited extent, cytomegalovirus. Quantitative results show considerable variation depending on such factors as the strain of virus, the cell culture system and the assay method, but in general the spectrum of herpesvirus sensitivities in descending order is: herpes simplex type 1 (most sensitive), herpes simplex type 2, varicella zoster virus, Epstein-Barr virus, and cytomegalovirus. Against herpes simplex types 1 and 2, acyclovir is generally more active in vitro than idoxuridine, trifluridine or vidarabine, and of similar potency to cytarabine. The comparative potencies of acyclovir and other antivirals against varicella zoster virus varied between studies. Idoxuridine, trifluridine and vidarabine all demonstrate greater activity in vitro than acyclovir against cytomegalovirus. A few studies have demonstrated additive or synergistic antiviral activity against herpesviruses in vitro when 1 of the other nucleoside analogue antivirals is combined with acyclovir. Acyclovir has also demonstrated some antiviral activity in vitro against a few other viruses but is inactive against vaccinia virus, Friend leukaemic virus, adenovirus type 5, a range of RNA viruses, and hepatitis B virus.
In in vivo animal models, acyclovir given by various routes of administration was effective against ocular infections, cutaneous infections, genital infections, encephalitis, and neonatal infections due to herpes simplex viruses. As would be expected, efficacy in these models varied somewhat with dosage, route, and frequency of administration, and correlated closely with the rapidity with which therapy was initiated following viral inoculation. When comparative studies were conducted in these models, acyclovir was at least as effective as other nucleoside analogue drugs, and in some models was more effective. Of particular interest, systemic acyclovir therapy of herpes simplex keratitis in rabbits and mice, cutaneous and genital herpes simplex infections in mice, and cutaneous herpes simplex infection in hamsters markedly reduced the death rates due to secondary encephalitis. Also, oral (200 or 400 mg/kg/day), subcutaneous (80 to 100 mg/kg/day) or intraperitoneal (80 mg/kg/day) administration, usually beginning within 24 or 48 hours after viral inoculation, increased the survival time or decreased the mortality rate in mice inoculated intracerebrally with herpes simplex virus.
In animal models, acyclovir has been shown to suppress the reactivation of latent herpes simplex virus residing in neural ganglia, but the drug does not eradicate latent virus which is already established. However, early initiation of topical or systemic therapy (usually within 24 hours of inoculation) has been shown to prevent the establishment of viral latency following primary infections in some instances, but such findings have not been duplicated in clinical trials (see below).
Resistant strains of herpes simplex types 1 and 2 virus and varicella zoster virus can be isolated readily in vitro; they have been isolated in animal models and clinically, in the latter case usually associated with prolonged intravenous therapy in immunocompromised patients. The number of patients with clinically resistant strains reported to date has been small, but the overall incidence of clinical resistance needs further clarification. However, because of the frequently decreased virulence of resistant strains arising during acyclovir treatment, these strains have often not been a clinical problem.
As with other nucleoside analogue antiviral drugs, the mechanism of action of acyclovir involves its inhibition of viral DNA replication.
Acyclovir is a highly selective inhibitor of herpesvirus DNA replication due to its enhanced uptake in herpesvirus-infected cells and phosphorylation by herpesvirus thymidine kinase, and to the substrate specificity of acyclovir triphosphate for viral, rather than cellular, DNA polymerase. The high specificity of acyclovir presumably accounts for its high therapeutic index.
Pharmacokinetic Studies: Multiple intravenous doses of acyclovir 5 mg/kg every 8 hours resulted in a steady-state mean peak plasma acyclovir concentration of 9.7 μg/ml, which should be clinically useful against herpes simplex types 1 and 2, varicella zoster, and Epstein-Barr virus infections. Oral absorption of acyclovir is limited (bioavailability ranges from 15 to 30%) and may involve a saturable process, but does not appear to be altered by food. Steady-state mean peak acyclovir plasma concentrations with oral administration of the recommended dose of 200mg every 4 hours were approximately 0.5 μg/ml. Systemic absorption with topical administration appears limited, but relatively high acyclovir concentrations (1.7 μg/ml) occurred in the aqueous humour with multidose ocular application of the 3% ointment every 5 hours.
In man, following multidose intravenous therapy with doses ranging from 400 to 1200 mg/m2 every 8 hours, acyclovir was detected in the kidney, lung, nervous tissue, liver, and heart. Cerebrospinal fluid and skin vesicle concentrations following intravenous therapy, and saliva concentrations following oral therapy were approximately 50%, 100% and 13% of simultaneous plasma concentrations, respectively. In vivo plasma protein binding of acyclovir varied from 9 to 24%, and was independent of plasma acyclovir concentration over the range 0.4 to 5.1 μg/ml.
In patients with normal renal function, approximately 15% of a dose of acyclovir is metabolised to an inactive metabolite, and the remainder is excreted in the urine unchanged. The elimination half-life in patients with normal renal function is 2 to 3 hours. In patients with end-stage renal impairment, drug plasma concentrations are increased and the elimination half-life is increased 7-fold, necessitating dosage adjustments. The elimination half-life also varies in patients in varying stages of renal impairment. The disposition of acyclovir in children is similar to that in adults, but in neonates the total body clearance is decreased by two-thirds and the elimination half-life is increased slightly.
Therapeutic Trials: In masked controlled studies in patients with herpetic ocular disease and dendritic ulcers, 3% acyclovir ointment was usually effective in over 95% of patients. Acyclovir was of comparable efficacy to 3% vidarabine ointment, and at least as effective as 0.5% and 1% idoxuridine ointment and 2% trifluridine ointment. However, acyclovir has not been compared with the usual dosage form of trifluridine (1% solution). As with other antiviral agents, acyclovir does not prevent recrudescent or recurrent ocular herpetic infection, or the development of deeper herpetic disease of the stroma and/or uvea. Although initial reports of efficacy in more difficult-to-treat geographic ulcers, and in deeper herpetic disease, are encouraging, only small numbers of such patients have been studied and confirmation of these early reports in comparative studies will be awaited with interest. A few open studies and case reports indicate that acyclovir may be useful in patients with herpetic ocular disease unresponsive to idoxuridine or vidarabine.
In non-immunocompromised patients, masked placebo-controlled studies have generally shown that topical (5% in polyethylene glycol or propylene glycol cream applied 4 to 6 times daily), oral (200mg 5 times daily) and intravenous acyclovir therapy (5 mg/kg every 8 hours), initiated at a pretreatment symptom duration of 3 to 4 days, significantly decreased the duration of viral shedding and the time to lesion healing in initial and in particular, primary initial genital herpes infections. However, effects on pain were less uniformly beneficial, especially with topical therapy, and recurrence rates were unaffected by topical or systemic therapy. Where non-primary initial infections were assessed separately, acyclovir ointment was of little benefit. When administered within 48 hours of initial symptoms of a recurrent infection or during the prodromal phase, both topical and oral acyclovir shortened the duration of viral shedding. Also oral acyclovir and acyclovir cream, but not acyclovir ointment demonstrated small but significant effects on healing. However, these effects were of questionable clinical importance due to the relatively short clinical course of untreated recurrent genital herpes. More interesting, however, was the successful prophylaxis of recurrent genital herpes with oral acyclovir 200mg, 3 or 4 times daily.
Topically administered acyclovir ointment was generally ineffective in treating herpes labialis infections in non-immunocompromised patients, whereas therapy with acyclovir cream resulted in a small but significant decrease in healing times, but without any accompanying reduction in pain or itching.
In non-immunocompromised patients, intravenous acyclovir, 500 mg/m2 or 5 mg/kg 3 times daily, significantly decreased the acute pain of herpes zoster and was of particular benefit in elderly patients. However, pain often recurred in patients who had experienced acute pain relief, and the treatment had no effect on postherpetic neuralgia. Nevertheless, if orally administered acyclovir can be convincingly shown to be similarly effective, its use in elderly patients, on an outpatient basis, would appear justified.
The efficacy of acyclovir in immunocompromised patients having herpes simplex virus infections (mainly of the lips, oral mucosa and face) has been assessed in several double-blind controlled studies. Both intravenous (250 mg/m2 every 8 hours) and topical (5% in polyethylene glycol applied 4 times daily) therapy were clinically beneficial in decreasing the duration of viral shedding and pain. However, only intravenous therapy significantly shortened the time to lesion healing. Both intravenous and oral acyclovir have been used with success prophylactically, to prevent the lesions due to reactivated latent herpes simplex virus in immunocompromised patients for the duration of drug administration. However, viral latency was not eradicated by the drug.
In a controlled study in immunocompromised patients, intravenous acyclovir 500 mg/m2 3 times daily for 7 days inhibited the progression of zoster infections. Also, the healing time and duration of viral shedding were shortened in patients presenting with disseminated cutaneous infections. However, neither acute nor postherpetic pain were significantly ameliorated. A multicentre, double-blind study of primary varicella infection in immunocompromised children showed a trend towards reduced visceral complications with intravenous acyclovir therapy (500 mg/m2 every 8 hours).
In a double-blind comparative study in immunocompromised patients with cytomegalovirus infections of various degrees of severity, there was a trend to reduced mortality rates with intravenously administered acyclovir (500 mg/m2 every 8 hours) compared with placebo, but the difference did not reach statistical significance. Generally acyclovir has shown little clinical therapeutic effect in the treatment of cytomegalovirus.
Data are either not available or incomplete as to the efficacy of acyclovir in herpes simplex encephalitis or cytomegalovirus infections in immunocompromised patients, and in infections due to Epstein-Barr virus or neonatal herpesvirus infections. However, encouraging case reports or small open studies have appeared and large controlled studies are currently underway in several of these difficult therapeutic areas.
Side Effects: Acyclovir therapy by ocular, topical, oral or intravenous routes has been well tolerated by most patients. With the 3% ophthalmic ointment, mild transient burning or stinging upon instillation (in up to 27% of patients), and reversible punctate epithelial staining with rose bengal (usually reported to occur in less than 25% of patients), occur most frequently. Also, punctal stenosis or occlusion, follicular conjunctivitis, contact blepharoconjunctivitis, palpebral allergy, or other signs of hypersensitivity have occurred occasionally, but side effects have only very rarely necessitated stopping the drug.
With acyclovir 5% topical ointment, mild pain, burning and stinging (about 30%) or pruritus (about 4%) are the most frequent adverse effects, but have not necessitated discontinuation of therapy in any patients in published studies. Rash and vulvitis (0.3% each) have also been reported. Systemic absorption following topical administration is limited.
Of 109 immunocompromised patients treated with oral acyclovir, the incidence, nature and severity of coryza (2 patients), dizziness, gastrointestinal discomfort, tiredness and diarrhoea (1 patient each) were similar to those reported with placebo. One case of renal colic was reported in a patient having a history of renal stones.
Intravenous acyclovir therapy has been most frequently associated with inflammation or phlebitis at the injection site following tissue infiltration of the intravenous fluid (approximately 15% incidence), transient elevations of serum creatinine (approximately 5%), and rash or hives (approximately 5%). The transient abnormalities of renal function occur more frequently following rapid bolus injection (10%), in patients with renal disease, in dehydrated patients, and with concomitant administration of other nephrotoxic drugs. Approximately 1% of patients manifest encephalopathic changes characterised by lethargy, obtundation, tremors, confusion, hallucinations, agitation, seizures, or coma. Transient abnormal liver function tests have occurred occasionally. Various other ‘side effects’ have been reported rarely in patients receiving acyclovir, but their association with drug therapy is uncertain. Only rarely has an adverse reaction necessitated withdrawal of therapy with intravenous acyclovir.
Dosage and Administration: For herpes simplex keratitis the recommended dosage of 3% acyclovir ophthalmic ointment is a 1cm ribbon placed inside the lower conjunctival sac every 4 hours while awake (5 times daily), and continued for at least 3 days after complete healing.
Acyclovir 5% topical ointment is recommended for initial herpes genitalis and in limited non-life-threatening mucocutaneous herpes simplex virus infections in immunocompromised patients. Application with a finger cot of a ‘ribbon’ of ointment about 1cm long per 10 cm2 surface area is recommended, beginning as soon as possible following the onset of signs and symptoms.
For the treatment of herpes simplex infections of the skin and mucous membranes, including initial and recurrent genital herpes, the recommended oral dosage is 200mg 5 times daily (approximately every 4 hours) for 5 days.
The recommended dosage of intravenous acyclovir therapy is 5 mg/kg, infused over 1 hour every 8 hours for 5 days (severe initial clinical episodes of genital herpes) or 7 days (mucosal and cutaneous herpes simplex virus types 1 and 2 infections in immunocompromised patients). Therapy should be initiated as soon as possible following the onset of signs and symptoms. Infusion concentrations lower than 7 mg/ml are recommended because higher concentrations may produce phlebitis or inflammation at the injection site upon extravasation, and infusions must be accompanied by adequate hydration in order to establish sufficient urine flow to prevent precipitation of the drug in the renal tubules. In children under 12 years of age, more accurate dosing can be obtained by infusing 250 mg/m2 over 1 hour, every 8 hours. Dosage reductions are necessary in patients with moderate to severe renal function impairment.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Alenius, S.; Berg, M.; Broberg, F.; Eklind, K.; Lindborg, B. and Öberg, B.: Therapeutic effects of foscarnet sodium and acyclovir on cutaneous infections due to herpes simplex virus type 1 in guinea pigs. Journal of Infectious Diseases 145: 569–573 (1982).
Alford, C.A.: Acyclovir treatment of herpes virus infections in immunocompromised humans. Proceedings of a symposium on acyclovir sponsored by Burroughs Wellcome and The National Institute of Allergy and Infectious Diseases, King et al. (Eds). American Journal of Medicine 73: 225–228 (1982).
Alford Jr, C.A.; Dolin, R.; Hirsch, M.S.; Karchmer, A.W. and Whitley, R.J.: Herpes simplex encephalitis and clinical trial design. Lancet 1: 1013 (1982).
Alford, C.A. and Whitley, R.J.: Treatment of infections due to herpes virus in humans: A critical review of the state of the art. Journal of Infectious Diseases 133: A101–A108 (1976).
Al-Nakib, W.; Al-Kandari, S.; El-Khalik, D.M.A. and El-Shirbiny, A.M.: A randomized controlled study of intravenous acyclovir (Zovirax*) against placebo in adults with chickenpox. Journal of Infection 6(Suppl. I): 49–56 (1983).
Anderson, J.R. and Field, H.J.: Development of retinitis in mice with non-fatal herpes simplex encephalitis. Neuropathology and Applied Neurobiology 8: 277–287 (1982).
Ashley, R.L.; Fife, K. and Corey, L.: Specific humoral immunity in patients receiving acyclovir treatment for primary genital herpes simplex virus (HSV) infections (abstract). Clinical Research 30: 361A (1982).
Bader, C.; Crumpacker, C.S.; Scnipper, L.E.; Ransil, B.; Clark, J.E.; Arndt, K. and Freedberg, I.M.: Natural history of recurrent facial-oral infection with herpes simplex virus. Journal of Infectious Diseases 138: 897–905 (1978).
Balfour, H.H.: Cytomegalovirus: The troll of transplantation. Archives of Internal Medicine 139: 279–280 (1979).
Balfour, H.H.; Bean, B.; Laskin, O.L.; Ambinder, R.F.; Meyers, J.D.; Wade, J.C.; Zaia, J.A.; Aeppli, D.; Kirk, L.E.; Segreti, A.C.; Keeney, R.E. and The Burroughs Wellcome Collaborative Acyclovir Study Group: Acyclovir halts progression of herpes zoster in immunocompromised patients. New England Journal of Medicine 308: 1448–1453 (1983).
Balfour, H.H.; Bean, B.; Mitchell, C.D.; Sachs, C.W.; Boen, J.R. and Edelman, C.K.: Acyclovir in immunocompromised patients with cytomegalovirus disease. Acyclovir Symposium. American Journal of Medicine 73: 241–248 (1982).
Bauer, D.J.: Treatment of plantar warts with acyclovir. Acyclovir Symposium. American Journal of Medicine 73: 313–314 (1982).
Bauer, D.J.; Collins, P.; Tucker, Jr W.E. and Macklin, A.W.: Treatment of experimental herpes simplex keratitis with acycloguanosine. British Journal of Ophthalmology 63: 429–435 (1979).
Bean, B.; Braun, C. and Balfour, H.H.: Acyclovir therapy for acute herpes zoster. Lancet 2: 118–121 (1982).
Biron, K.K. and Elion, G.B.: In vitro susceptibility of varicella zoster to acyclovir. Antimicrobial Agents and Chemotherapy 18: 443–447 (1980).
Biron, K.K. and Elion, G.B.: Effect of acyclovir combined with other antiherpetic agents on varicella zoster virus in vitro. Acyclovir Symposium. American Journal of Medicine 73: 54–57 (1982).
Biron, K.K.; Fyfe, J.A.; Noblin, J.E. and Elion, G.B.: Selection and preliminary characterization of acyclovir-resistant mutants of varicella zoster virus. Acyclovir Symposium. American Journal of Medicine 73: 383–386 (1982a).
Biron, K.K.; Noblin, J.E.; de Miranda, P. and Elion, G.B.: Uptake, distribution, and anabolism of acyclovir in herpes simplex virus-infected mice. Antimicrobial Agents and Chemotherapy 21: 44–50 (1982b).
Blum, R.M.; Liao, S.H.T. and de Miranda, P.: Overview of acyclovir pharmacokinetic disposition in adults and children. Acyclovir Symposium. American Journal of Medicine 73: 186–192 (1982).
Blyth, W.A.; Harbour, D.A. and Hill, T.J.: Effect of acyclovir on recurrence of herpes simplex skin lesions in mice. Journal of General Virology 48: 417–419 (1980).
Boiron, M.; Devergie, A. and Gluckman, E.: Traitement par acyclovir des infections du groupe herpes chez des sujets immunosupprimes traites par greffe de moelle. Infection Herpetique Humaine et Ses Traitements, Brest, 26–28 March (1981).
Boulter, E.A.; Thornton, B.; Bauer, DJ. and Bye, A.: Successful treatment of experimental B virus (herpesvirus simiae) infection with acyclovir. British Medical Journal 280: 681–683 (1980).
Brigden, D.; Fiddian, P.; Rosling, A.E. and Ravenscroft, T.: Acyclovir — a review of the preclinical and early clinical data of a new antiherpes drug. Antiviral Research 1: 203–212 (1981).
Brigden, D.; Fowle, A. and Rosling, A.: Acyclovir, a new antih-erpetic drug: Early experience in man with systemically administered drug; in Collier, L.H. and Oxford, J. (Eds.) Developments in Antiviral Therapy, pp. 53–62 (Academic Press, London 1980).
Brigden, D.; Rosling, A.E. and Woods, N.C.: Renal function after acyclovir intravenous injection. Acyclovir Symposium. American Journal of Medicine 73: 182–185 (1982).
Bryson, Y.J.; Dillon, M.; Lovett, M.; Acuna, G.; Taylor, S.; Cherry, J.D.; Johnson, L.B.; Weismeier, E.; Growdon, W.; Creagh-Kirk, T. and Keeney, R.: Treatment of first episodes of genital herpes simplex virus infection with oral acyclovir. New England Journal of Medicine 308: 916–921 (1983).
Burns, W.H.; Saral, R.; Santos, C.W.; Laskin, O.L.; Lietman, P.S.; McLaren, C. and Barry, D.W.: Isolation and characterisation of resistant herpes simplex virus after acyclovir therapy. Lancet 1: 421–423 (1982a).
Burns, W.M.; Wingard, J.R.; Bender, W.J. and Saral, R.: Thymidine kinase not required for antiviral activity of acyclovir against mouse cytomegalovirus. Journal of Virology 39: 889–893 (1981).
Burns, W.H.; Wingard, J.R.; Sandford, G.R.; Bender, W.J. and Saral, R.: Acyclovir in mouse cytomegalovirus infections. Acyclovir Symposium. American Journal of Medicine 73: 118–124 (1982b).
Campbell, M.; Klapper, P.E. and Longson, M.: Acyclovir in herpes encephalitis. Lancet 1: 38 (1982).
Cheng, Y.; Dutschman, G.; Fox, J.J.; Watanabe, K.A. and Machida, H.: Differential activity of potential antiviral nucleoside analogs on herpes simplex virus-induced and human cellular thymidine kinases. Antimicrobial Agents and Chemotherapy 20: 420–423 (1981).
Cho, C.T. and Feng, K.K.: Combined effects of acycloguanosine and humoral antibodies in experimental encephalitis due to herpesvirus hominis. Journal of Infectious Diseases 142: 451 (1980).
Chou, S.; Gallagher, J.G. and Merigan, T.C.: Controlled clinical trial of intravenous acyclovir in heart-transplant patients with mucocutaneous herpes simplex infections. Lancet 1: 1392–1394 (1981).
Clive, D.; Turner, N.T.; Hozier, J.; Batson, A.G. and Tucker, W.E. Jr: Preclinical toxicology studies with acyclovir: Genetic toxicity tests. Fundamental and Applied Toxicology (In press, 1983).
Coen, D.M. and Gelep, P.T.: Adenine arabinoside resistant mutants of HSV-1; in Kaplan et al. (Eds) International Workshop on Herpesviruses, Bologna, 27–31 July (1981), p. 210 (Esculapio Publishing Company, Bologna 1981).
Coen, D.M. and Schaffer, P.A.: Two distinct loci confer resistance to acycloguanosine in herpes simplex virus type 1. Proceedings of the National Academy of Science USA 77: 2265–2269 (1980).
Colby, B.M.; Shaw, J.E.; Elion, G.B. and Pagano, J.S.: Effect of acyclovir [9-(2-Hydroxyethoxymethyl) guanine] on Epstein-Barr virus DNA replication. Journal of Virology 34: 560–568 (1980).
Colby, B.M.; Shaw, J.E.; Datta, A.K. and Pagano, J.S.: Replication of Epstein-Barr virus DNA in lymphoblastoid cells treated for extended periods with acyclovir. Acyclovir Symposium. American Journal of Medicine 73: 77–81 (1982).
Colin, J.; Chastel, C.; Quillien, M.C. and Renard, G.: Traitement comparé de la kératite herpétique expérimentale du lapin par l’idoxuridine et l’acyclovir: Corrélations cliniques, virologiques et histopathologiques. Journal Française Ophthalmologique. 4: 33–44 (1981a).
Colin, J.; Chastel, C.; Renard, G. and Cantell, K.: Combination therapy for dendritic keratitis with human leucocyte interferon and acyclovir. American Journal of Ophthalmology 95: 346–348 (1983).
Colin, J.; Tournoux, A.; Chastel, C. and Renard, G.: Kératite herpétique superficielle. Traitement comparatif en double insu par acyclovir et idoxuridine. Nouvelle Presse Médicale 36: 2969–2975 (1981b).
Collins, P.; Appleyard, G. and Oliver, N.M.: Sensitivity of herpes virus isolates from acyclovir clinical trials. Acyclovir Symposium. American Journal of Medicine 73: 380–382 (1982).
Collins, P. and Bauer, D.J.: Activity in vitro against herpes virus of 9-(2-hydroxyethoxymethyl) guanine (acycloguanosine), a new antiviral. Journal of Antimicrobial Chemotherapy 5: 431–436 (1979).
Collins, P. and Oliver, N.M.: Acyclovir treatment of cutaneous herpes in guinea pigs and herpes encephalitis in mice. Acyclovir Symposium. American Journal of Medicine 73: 96–99 (1982).
Collins, P.; Tisdale, S.M. and Furman, P.A.: Electron microscopic study of the effects of acyclovir on the in vitro replication on herpes simplex virus; in Nelson, J.D. and Grassi, C. (Eds) Current Chemotherapy and Infectious Disease: Proceedings of the 11th International Congress of Chemotherapy and the 19th Interscience Conference on Antimicrobial Agents and Chemotherapy, Boston, 1–5 October (1979) vol. II, pp. 1383–1385 (American Society for Microbiology, Washington DC 1980).
Collum, L.M. and Benedict-Smith, A.: Acyclovir (Zovirax) in herpes simplex keratitis. Herpetisch Augener Krankungen, p. 323 (J.F. Bergmann Verlag, Munchen 1981).
Collum, L.M.T.; Benedict-Smith, A. and Hillary, I.B.: Randomised double-blind trial of acyclovir and idoxuridine in dendritic corneal ulceration. British Journal of Ophthalmology 64: 766–769 (1980).
Collum, L.M.T. and Logan, P.: Acyclovir in complicated herpetic keratitis (abstract). Irish Journal of Medical Science 151: 291–292 (1982).
Collum, L.M.T.; Logan, P.; Hillary, I.B. and Ravenscroft, T.: Acyclovir in herpes keratitis. Acyclovir Symposium. American Journal of Medicine 73: 290–293 (1982a).
Collum, L.M.T.; Logan, P. and Ravenscroft, T.: Acyclovir (Zo-virax) in herpetic disciform keratitis. British Journal of Ophthalmology 67: 115–118 (1983).
Corey, L.; Benedetti, J.K.; Critchlow, C.W.; Remington, M.R.; Winter, C.A.; Fahnlander, A.L.; Smith, K.; Salter, D.L:; Keeney, R.E.; Davis, L.G.; Hintz, M.A.; Connor, J.D. and Holmes, K.K.: Double-blind controlled trial of topical acyclovir in genital herpes simplex virus infections. Acyclovir Symposium. American Journal of Medicine 73: 326–334 (1982a).
Corey, L.; Adams, H.G.; Brown, Z.A and Holmes, K.K.: Genital herpes simplex virus infections: Clinical manifestations, course, and complications. Annals of Internal Medicine 98: 958–972 (1983a).
Corey, L. and Holmes, K.K.: Genital herpes simplex virus infections: Current concepts in diagnosis, therapy and prevention. Annals of Internal Medicine 98: 973–983 (1983).
Corey, L.; Fife, K.H.; Benedetti, J.K.; Winter, C.A.; Fahnlander, A.; Conner, J.D.; Hintz, M.A. and Holmes, K.K.: Intravenous acyclovir for the treatment of primary genital herpes. Annals of Internal Medicine 98: 914–921 (1983b).
Corey, L.; Holmes, K.K.; Benedetti, J. and Critchlow, C: Clinical course of genital herpes: Implications for therapeutic trials; in Nahmias (Ed.) The Human Herpesvirus: An Interdisciplinary Prospective: Proceedings International Conference Human Herpesviruses, Atlanta, 17–21 March (1980), pp. 496–502 (Elsevier, New York 1981).
Corey, L.; Nahmias, A.J.; Guinan, M.E.; Benedetti, J.K.; Critchlow, C.W. and Holmes, K.K.: Trial of topical acyclovir in genital herpes simplex virus infections. New England Journal of Medicine 306: 1313–1319 (1982b).
Coster, D.J.; Wilhelmus, K.R.; Michaud, R. and Jones, B.R.: Comparison of acyclovir and idoxuridine as treatment for ulcerative herpetic keratitis. British Journal of Ophthalmology 64: 763–765 (1980).
Crumpacker, C.S.; Chartrand, P.; Subak-Sharpe, J.H. and Wilkie, N.M.: Resistance of herpes simplex virus to acycloguanosinegenetic and physical analysis. Virology 105: 171–184 (1980).
Crumpacker, C. and Kowalsky, P.: Physical mapping of mutations for resistance to (Ara-A) and (BVDU) within the HSV DNA polymerase locus; in Kaplan et al. (Eds) International Workshop on Herpesviruses, Bologna, 27–31 July (1981), p. 50 (Esculapio Publishing Company, Bologna 1981).
Crumpacker, C.S.; Schnipper, L.E.; Kowalsky, P.N. and Sherman, D.M.: Resistance of herpes simplex virus to adenine arabinoside and ∈-5-(2-bromovinyl)-2′-deoxyuridine: A physical analysis. Journal of Infectious Diseases 146: 167–172 (1982a).
Crumpacker, C.S.; Schnipper, L.E.; Zaia, J.A. and Levin, M.J.: Growth inhibition by acycloguanosine of herpesviruses isolated from human infections. Antimicrobial Agents and Chemotherapy 15: 642–645 (1979).
Crumpacker, C.S.; Schnipper, L.E.; Marlowe, S.I.; Kowalsky, P.N.; Hershey, B.J. and Levin, M.J.: Resistance to antiviral drugs of herpes simplex virus isolated from a patient treated with acyclovir. New England Journal of Medicine 306: 343–346 (1982b).
Cupps, T.R.; Strauss, S.E. and Waldmann, T.A.: Successful treatment with acyclovir of an immunodeficient patient infected simultaneously with multiple herpesviruses. American Journal of Medicine 70: 882–886 (1981).
Daniel, M.D.; Falk, L.A.; King, N.W.; Tamulevich, R.; Holland, J.S. and Bekasi, G.: Comparative studies of interferon and three antiviral agents on neurotropic and oncogenic herpesviruses. Antimicrobial Agents and Chemotherapy 18: 622–628 (1980).
Darby, G.; Field, H.J. and Salisbury, S.A.: Altered substrate specificity of herpes simplex virus thymidine kinase confers acyclovir resistance. Nature 289: 81–83 (1981).
Davidson, R.L.; Kaufman, E.R.; Crumpacker, C.S. and Schnipper, L.E.: Inhibition of herpes simplex virus transformed and nontransformed cells by acycloguanosine: Mechanisms of uptake and toxicity. Virology 113: 9–19 (1981).
Davis, L.G. and Keeney, R.E.: Genital herpes simplex virus infection: Clinical course and attempted therapy. American Journal of Hospital Pharmacists 38: 825–829 (1981).
De Clercq, E.: Selective antiherpes agents. Trends in Pharmacological Sciences 3: 492–495 (1982a).
De Clercq, E.; Descamps, J.; De Somer, P.; Barr, P.J.; Jones, A.S. and Walker, R.T.: (∈)-5-(2-Bromovinyl)-2′-deoxyuridine: A potent and selective anti-herpes agent. Proceedings of the National Academy of Sciences USA 76: 2947–2951 (1979).
De Clercq, E.; Descamps, J.; Ogata, M. and Shigeta, S.: In vitro susceptibility of varicella zoster virus to ∈-5-(2-bromovinyl)-2′-deoxyuridine and related compounds. Antimicrobial Agents and Chemotherapy 21: 33–38 (1982b).
De Clercq, E., Descamps, J.; Verfielst, G.; Walker, R.T.; Jones, A.S.; Torrence, P.F. and Shugar, D.: Comparative efficacy of antiherpes drugs against different strains of herpes simplex virus. Journal of Infectious Diseases 141: 563–674 (1980a).
De Clercq, E.; Descamps, J.; Verhelst, G.; Jones, A.S. and Walker, R.T.: Antiviral activity of 5-(2-halogenovinyl)-2′-deoxyuridines; in Nelson, J.D. and Grassi, C. (Eds) Current Chemotherapy and Infectious Disease: Proceedings of the 11th International Congress of Chemotherapy and the 19th Interscience Conference on Antimicrobial Agents and Chemotherapy, Boston, 1–5 October (1979), vol. II, pp. 1372–1374 (American Society for Microbiology, Washington DC 1980b).
De Clercq, E.; Heremans, H.; Descamps, J.; Verhelst, G.; De Ley, M. and Billiau, A.: Effects of ∈-5-(2-bromovinyl)-2′-deoxyuridine and other selective anti-herpes compounds on the induction of retrovirus particles in mouse BALB/3T3 cells. Molecular Pharmacology 19: 122–129 (1981).
de Miranda, P. and Good, S.S.: Biotransformation of acyclovir to 9-carboxymethoxy-methylguanine (abstract). Federation Proceedings 41: 1733 (1982).
de Miranda, P.; Good, S.S.; Krasny, H.C.; Connor, J.D.; Laskin, O.L. and Lietman, P.S.: Metabolic fate of radioactive acyclovir in humans. Acyclovir Symposium. American Journal of Medicine 73: 215–220 (1982a).
de Miranda, P.; Krasny, H.C.; Page, D.A. and Elion, G.B.: Disposition of acyclovir in different species. Journal of Pharmacology and Experimental Therapeutics 219: 309–315 (1981).
de Miranda, P.; Krasny, H.C.; Page, D.A. and Elion, G.B.: Species differences in the disposition of acyclovir. Acyclovir Symposium. American Journal of Medicine 73: 31–35 (1982b).
de Miranda, P.; Whitley, R.J.; Barton, N.; Page, D.; Creagh-Kirk, T.; Liao, S. and Blum, R.: Systemic absorption and pharmacokinetics of acyclovir (ACV) [Zovirax] capsules in immunocompromised patients with herpesvirus infections (abstract). 22nd Interscience Conference on Antimicrobial Agents and Chemotherapy, Florida, 4–6 October (1982c).
de Miranda, P.; Whitley, R.J.; Blum, M.R.; Keeney, R.E.; Barton, N.; Cocchetto, D.M.; Good, S.; Hemstreet, G.P.; Kirk, L.E.; Page, D.A. and Elion, G.B.: Acyclovir kinetics after intravenous infusion. Clinical Pharmacology and Therapeutics 26: 718–728 (1979).
Derse, D. and Cheng, Y.C.: 3′–5′ DNA exonuclease associated with herpes simplex virus type 1 (HSV-1) DNA polymerase: Properties and role in anti-viral chemotherapy (abstract). Federation Proceedings 40: 667 (1981).
Descamps, J.; De Clercq, E.; Barr, P.J.; Jones, A.S.; Walker, R.T.; Torrence, P.F. and Shugar, D.: Relative potencies of different anti-herpes agents in the topical treatment of cutaneous herpes simplex virus infection of athymic nude mice. Antimicrobial Agents and Chemotherapy 16: 680–682 (1979).
Devergie, A.; Gluckman, E.; Lotsberg, J-; Zhao, X.M.; Gomez-Morales, M.; Mazeron, M.C. and Perol, Y.: Oral acyclovir prophylactic treatment of herpes simplex infection after bone marrow transplantation. Preliminary results. Experimental Hematology 11(Suppl. XIII): 117–119 (1983).
Elion, G.B.: Mechanism of action and selectivity of acyclovir. Acyclovir Symposium. American Journal of Medicine 73: 7–13 (1982a).
Elion, G.B.: Advances in antiviral chemotherapy; in Yoshida et al. (Eds) Advances in Pharmacology and Therapeutics II, vol. 6, pp. 3–17 (Pergamon Press, Oxford and New York 1982b).
Epstein, M. A.: An assessment of the possible role of virus in the aetiology of Burkitt’s lymphoma. Progress in Experimental Tumour Research 21: 72 (1978).
Falcon, M.G. and Jones, B.R.: Acycloguanosine: Antiviral activity in the rabbit cornea. British Journal of Ophthalmology 63: 422–424 (1979).
Feighny, R.J.; Henry, II B.E.; Datta, A.K. and Pagano, J.S.: Induction of DNA polymerase activity after superinfection of raji cells with Epstein-Barr virus. Virology 107: 415–423 (1980).
Fiddian, A.P. and Ivanyi, L.: Topical acyclovir in the management of recurrent herpes labialis. British Journal of Dermatology 109 (In press, 1983).
Fiddian, A.P.; Kinghorn, G.R.; Goldmeier, D.; Rees, E.; Rodin, P.; Thin, R.N.T. and de Koning, G.A.J.: Topical acyclovir in the treatment of genital herpes: A comparison with systemic therapy. Journal of Antimicrobial Chemotherapy (In press, 1983a).
Fiddian, A.P.; Yeo, J.M.; Stubbings, R. and Dean, D.: Successful treatment of herpes labialis with topical acyclovir. British Medical Journal 286: 1699–1701 (1983b).
Field, H.; McMillan, A. and Darby, G.: Sensitivity of acyclovirresistant mutants of herpes simplex virus to other antiviral drugs. Journal of Infectious Diseases 143: 281–285 (1981a).
Field, H.; McMillan, A. and Darby, G.: Cross-resistance of acyclovir-resistant mutants of herpes simplex virus; in Gauri, K.K. (Ed.) Antiviral Chemotherapy: Design of Inhibitors of Viral Functions: Proceedings of the Symposium on Antiviral Chemotherapy (1980), pp. 179–183 (Academic Press, New York 1981b).
Field, H.J.: Development of clinical resistance to acyclovir in herpes simplex infected mice receiving oral therapy. Antimicrobial Agents and Chemotherapy 21: 744–752 (1982).
Field, H.J.; Anderson, J.R. and Wildy, P.: Atypical patterns of neural infection produced in mice by drug-resistant strains of herpes simplex virus. Journal of General Virology 59: 91–99 (1982a).
Field, H.J.; Bell, S.E.; Elion, G.B.; Nash, A.A. and Wildy, P.: Effect of acycloguanosine treatment on acute and latent herpes simplex infections in mice. Antimicrobial Agents and Chemotherapy 15: 554–561 (1979).
Field, H.J. and Darby, G.: Pathogenicity in mice of strains of herpes simplex virus which are resistant to acyclovir in vitro and in vivo. Antimicrobial Agents and Chemotherapy 17: 209–216 (1980).
Field, H.J.; Darby, G. and Wildy, P.: Isolation and characterization of acyclovir resistant mutants of herpes simplex virus. Journal of General Virology 49: 115–124 (1980).
Field, H.J. and De Clercq, E.: Effects of oral treatment with acyclovir and bromovinyldeoxyuridine on the establishment and maintenance of latent herpes simplex virus infection in mice. Journal of General Virology 56: 259–165 (1981).
Field, H.J.; Larder, B.A. and Darby, G.: Isolation and characterization of acyclovir-resistant strains of herpes simplex virus. Acyclovir Symposium. American Journal of Medicine 73: 369–371 (1982b).
Field, H.J. and Neden, J.: Isolation of bromovinyldeoxyuridine-resistant strains of herpes simplex virus and successful chemotherapy of mice infected with one such strain by using acyclovir. Antiviral Research 2: 243–254 (1982).
Field, H.J. and Wildy, P.: The pathogenicity of thymidine kinase deficient mutants of herpes simplex virus in mice. Journal of Hygiene 81: 267–277 (1978).
Field, H.J. and Wildy, P.: Recurrent herpes simplex: The outlook for systemic antiviral agents. British Medical Journal 282: 1821–1822 (1981).
Fife, K.H.; Corey, L.; Keeney, R.E.; Winter, C.A.; Fahnlander, A.; Davis, L.G. and Holmes, K.K.: Double blind placebo controlled trial of intravenous acyclovir for severe primary genital herpes (abstract). 21st Interscience Conference on Antimicrobial Agents and Chemotherapy, Chicago, 4–6 November (1981).
Forman, M.S.: Use of acyclovir for the recovery of CMV from specimens containing HSV (abstract). American Society of Microbiologists, Atlanta, 7–12 March (1982).
Furman, P.A.; Coen, D.M.; St Clair, M.H. and Schaffer, P.A: Acyclovir-resistant mutants of herpes simplex virus type 1 express altered DNA polymerase or reduced acyclovir phosphorylating activities. Journal of Virology 40: 936–941 (1981a).
Furman, P.A.; McGuirt, P.V.; Keller, P.M.; Fyfe, J.A. and Elion, G.B.: Inhibition by acyclovir of cell growth and DNA synthesis of cells biochemically transformed with herpes virus genetic information. Virology 102: 420–430 (1980a).
Furman, P.A.; St Clair, M.H.; Fyfe, J.A.; Rideout, J.L.; Keller, P.M. and Elion, G.B.: Inhibition of herpes simplex virus-induced DNA polymerase activity and viral DNA replication and viral DNA replication by 9-(2-hydroxyethoxymethyl) guanine and its triphosphate. Journal of Virology 32: 72–77 (1979).
Furman, P.A.; de Miranda, P.; St Clair, M.H. and Elion, G.B.: Metabolism of acyclovir in virus-infected and uninfected cells. Antimicrobial Agents and Chemotherapy 20: 518–524 (1981b).
Fyfe, J. and Biron, K.: Phosphorylation of acyclovir by a thymidine kinase induced by varicella zoster virus; in Nelson, J.D. and Grassi, C. (Eds) Current Chemotherapy and Infectious Disease: Proceedings of the 11th International Congress of Chemotherapy and the 19th Interscience Conference on Antimicrobial Agents and Chemotherapy, Boston, 1–5 October (1979) vol. II, pp. 1378–1379 (American Society for Microbiology, Washington DC 1980).
Fyfe, J.A.; Biron, K.K.; McKee, S.A.; Kelly, C.M.; Elion, G.B. and Soike, K.F.: Activation and antiviral effect of acyclovir in cells infected with a varicella-like simian virus. Acyclovir Symposium. American Journal of Medicine 73: 58–61 (1982).
Fyfe, J.A.; Keller, P.M.; Furman, P.A.; Miller, R.L. and Elion, G.B.: Thymidine kinase from herpes simplex virus phosphorylates the new antiviral compound, 9-(2-hydroxyethoxymethyl) guanine. Journal of Biological Chemistry 253: 8721–8727 (1978).
Galasso, G.J.: An assessment of antiviral drugs for the management of infectious diseases in humans. Antiviral Research 1: 73–96 (1981).
Gale, R.P.; Champlin, R.E.; Fieg, S.A. and Fitchen, J.H.: Aplastic anemia: Biology and treatment. Annals of Internal Medicine 95: 477–494 (1981).
Gibson, J.R.; Harvey, S.G.; Barth, J.; Darley, C.R.; Reshad, H. and Burke, C.A.: A comparison of acyclovir cream versus liquid nitrogen versus placebo cream in the treatment of viral plantar warts. British Journal of Dermatology 109: 46 (1983).
Glasgow, L.A.; Richards, J.T. and Kern, E.R.: Effect of acyclovir treatment on acute and chronic murine cytomegalovirus infection. Acyclovir Symposium. American Journal of Medicine 73: 132–137 (1982).
Goldman, J.M.; Chipping, P.M.; Agnarsdottir, G. and Brigden, D.: Acycloguanosine for viral pneumonia. Lancet 1: 820 (1979).
Green, M.T.; Dunkel, E.C. and Morris, B.L.: Quantitation of herpes simplex virus type 1 shed in preocular tear film of rabbits treated with acyclovir. Antimicrobial Agents and Chemotherapy 20: 580–582 (1981).
Halsos, A.M.; Gavrielsen, B.O. and Fiddian, A.P.: Suppression of recurrences of genital herpes in frequent sufferers. 2nd International Acyclovir (Zovirax) Symposium, London, 15–28 May (1983).
Hammer, S.M.; Kaplan, J.C.; Lowe, B.R. and Hirsch, M.S.: Alpha interferon and acyclovir treatment of herpes simplex virus in lymphoid cell cultures. Antimicrobial Agents and Chemotherapy 21: 634–640 (1982).
Hanto, D.W.; Frizzera, G.; Gajl-Peczalska, K.J.; Sakamoto, K.; Purtilo, D.T.; Balfour Jr, H.H.; Simmons, R.L. and Najarian, J.S.: Epstein-Barr virus-induced B-cell lymphoma after renal transplantation. Acyclovir therapy and transition from polyclonal to monoclonal β-cell proliferation. New England Journal of Medicine 306: 913–918 (1982).
Hanto, D.W.; Frizzera, G.; Purtilo, D.T.; Sakamoto, K.; Sullivan, J.L.; Saemundsen, A.K.; Klein, G.; Simmons, R.L. and Najarian, J.S.: Clinical spectrum of lymphoproliferative disorders in renal transplant recipients and evidence for the role of Epstein-Barr virus. Cancer Research 41: 4253–4261 (1981).
Harmenberg, J. and Wahren, B.: Influence of cell culture conditions on the inhibition of herpes simplex virus type 1 replication by acyclovir. Intervirology 17: 215–221 (1982).
Harmenberg, J.; Wahren, B. and Öberg, B.: Influence of cells and virus multiplicity on the inhibition of herpesvirus with acycloguanosine. Intervirology 14: 23–224 (1980).
Heaton, A.; Arze, R.S. and Ward, M.K.: Acyclovir for life-threatening herpes simplex virus infection after renal transplantation. Lancet 2: 875 (1981).
Herrmann Jr, E.C. and Herrmann, J.A.: Diagnosis of viral disease and the advent of antiviral drugs. Pharmacology and Therapeutics 7: 35–69 (1979).
Hill, J.M.; Kwon, B.S.; Burch, K.D.; Deback, J.; Whang, I.; Jones, G.T.; Luke, B.; Harp, R.; Shimomura, Y.; Hull, D.S. and Gangarosa, L.P.: Acyclovir and vidarabine monophosphate: Comparison of iontophoretic and intravenous administration for the treatment of HSV-l stromal keratitis. Acyclovir Symposium. American Journal of Medicine 73: 300–304 (1982).
Hill, T.J.; Blyth, W.A. and Harbour, D.A.: Recurrent herpes simplex in mice; topical treatment with acyclovir cream. Antiviral Research 2: 135–146 (1982).
Hintz, M.; Connor, J.D.; Spector, S.A.; Blum, M.R.; Keeney, R.E. and Yeager, A.S.: Neonatal acyclovir pharmacokinetics in patients with herpes virus infections. Acyclovir Symposium. American Journal of Medicine 73: 210–214 (1982).
Ho, M.: Cytomegalovirus; in Mandell et al. (Eds) Principles and Practice of Infectious Diseases, pp. 1307–1323 (Wiley Medical Publishing, New York 1979).
Honess, R.W.; O’Hare, P. and Young, D.: Comparison of thymidine kinase activities induced in cells productively infected with herpesvirus saimiri and herpes simplex virus. Journal of General Virology 58: 237–249 (1982).
Jensen, K.B.; Nissen, S.H. and Jessen, F.: Acyclovir in the treatment of herpetic keratitis. Acta Ophthalmologica 60: 557–563 (1982).
Jones, B.R.; Coster, D.J. and Falcon, M.G.: Topical therapy of ulcerative herpetic keratitis with human interferon. Lancet 2: 128 (1976).
Jones, B.R.; Fison, P.N.; Cobo, L.M.; Coster, D.J.; Thompson, G.M. and Falcon, M.G.: Efficacy of acycloguanosine (Wellcome 2484) against herpes-simplex corneal ulcers. Lancet 1: 243–244 (1979).
Juel-Jensen, B.E.; Khan, J.A. and Pasvol, G.: High dose acyclovir in the treatment of zoster: A double-blind placebo-controlled trial. Journal of Infection 6(Suppl. I): 31–36 (1983).
Kaufman, H.E.: Local therapy of herpes simplex virus ocular infections; in Nahmias, et al. (Eds) The Human Herpesvirus: An Interdisciplinary Prospective: Proceedings International Conference Human Herpesviruses, Atlanta, 17–21 March (1980), pp. 466–477 (Elsevier, New York 1981).
Kaufman, H.E.; Varnell, E.D.; Centifanto, Y.M. and Rheinstrom, S.D.: Effect of 9-(2-hydroxyethoxymethyl) guanine on herpesvirus induced keratitis and iritis in rabbits. Antimicrobial Agents and Chemotherapy 14: 842–845 (1978).
Kennedy, C.T.; Leigh, I.M.; Ridgway, H.A.; Wansbrough-Jones, M.H. and Brigden, D.: Treatment of erythema multiforme secondary to herpes simplex by prophylactic topical acyclovir. British Medical Journal 283: 1360–1361 (1981).
Kern, E.R.: Acyclovir treatment of experimental genital herpes simplex virus infections. Acyclovir Symposium. American Journal of Medicine 73: 100–108 (1982).
Kern, E.R., Richards, J.T.; Glascow, L.A.; Overall, J.C. and de Miranda, P.: Optimal treatment of herpes simplex virus encephalitis in mice with oral acyclovir. Acyclovir Symposium. American Journal of Medicine 73: 125–131 (1982).
Kinney, T.R.; Gutman, L.T.; Wilfert, C.M.; Keeney, R.; de Miranda, P.; Rudd, C. and Falletta, J.M.: Acyclovir: Therapy of varicella zoster infections in children with malignancies (abstract). Pediatric Research 15: 580 (1981).
Klauber, A. and Ottovay, E.: Acyclovir and idoxuridine treatment of herpes simplex keratitis — a double blind clinical study. Acta Ophthalmologica 60: 838–844 (1982).
Klein, R.J.; de Stefano, E.; Friedman-Kien, A.E. and Brady, E.: Effect of acyclovir on latent herpes simplex virus infections in trigeminal ganglia of mice. Antimicrobial Agents and Chemotherapy 19: 937–939 (1981a).
Klein, R.J. and Friedman-Kien, A.E.: Dimethylsulfoxide as a vehicle for antiviral agents in herpes simplex virus skin infections in hairless mice. Proceedings of the 11th International Congress of Chemotherapy and the 19th Interscience Conference on Antimicrobial Agents and Chemotherapy, Boston, 1–5 October (1979), vol. II, pp. 1374–1376 (American Society for Microbiology, Washington DC 1980).
Klein, R.J. and Friedman-Kien, A.E.: Pathogenesis of infection with drug-resistant herpes simplex virus (HSV) mutants in mice (abstract). Annual Meeting American Society of Microbiologists, Dallas, 1–6 March (1981).
Klein, R.J.; Friedman-Kien, A.E. and De Stefano, E.: Latent herpes simplex virus infections in sensory ganglia of hairless mice prevented by acycloguanosine. Antimicrobial Agents and Chemotherapy 15: 723–729 (1979).
Klein, R.J.; Friedman-Kien, A.E. and de Stefano, E.: Pathogenesis of experimental skin infection induced by drug-resistant herpes simplex virus mutants. Infection and Immunity 34: 693–701 (1981b).
Knopf, K.W.; Kaufman, E.R. and Crumpacker, C.: Physical mapping of drug resistance mutations defines an active center of the herpes simplex virus DNA polymerase enzyme. Journal of Virology 39: 746–757 (1981).
Krasny, H.C.; Liao, S.H.T.; Good, S.S.; Petty, B. and Lietman, P.S.: Oral pharmacokinetics and metabolism of the prodrug of acyclovir, Al34U, in humans. Clinical Pharmacology and Therapeutics 33: 256 (1983).
Laibson, P.R.; Pavan-Langston, D.; Yeakley, W.R. and Lass, J.: Acyclovir and vidarabine for the treatment of herpes simplex keratitis. Acyclovir Symposium. American Journal of Medicine 73: 281–285 (1982).
La Lau, C.; Oosterhuis, J.A.; Versteeg, J.; Van Rijk, G.; Renardel De Lavalette, J.G.C.; Craandijk, A. and Lamers, W.P.M.A.: Acyclovir and trifluorothymidine in herpetic keratitis: A multicentre trial. British Journal of Ophthalmology 66: 506–508 (1982a).
La Lau, C.L.; Oosterhuis, J.A.; Versteeg, J.; Van Rij, G.; Renardel De Lavalette, J.G.C.; Crandijk, A.; Lamers, W.R.M.J. and Mierlobensteyn, T.: Multicenter trial of acyclovir and trifluorothymidine in herpetic keratitis. Acyclovir Symposium. American Journal of Medicine 73: 305–306 (1982b).
Land, G. and Bye, A.: Simple high-performance liquid Chromatographic method for the analysis of 9-(2-hydroxyethoxymethyl) guanine (acyclovir) in human plasma and urine. Journal of Chromatography 224: 51–58 (1981).
Landry, M.L.; Lucia, H.L.; Hsiung, G.D.; Pronovost, A.D.; Dann, P.R.; August, M.J. and Mayo, D.R.: Effect of acyclovir on genital infection with herpes simplex virus types 1 and 2 in the guinea pig. Acyclovir Symposium. American Journal of Medicine 73: 143–150 (1982).
Lang, D.J. and Cheung, K.: Effectiveness of acycloguanosine and trifluorothymidine as inhibitors of cytomegalovirus infection in vitro. Acyclovir Symposium. American Journal of Medicine 73: 49–53 (1982).
Laskin, O.L.: Acyclovir kinetics. Clinical Pharmacokinetics 8: 187–201 (1983).
Laskin, O.L.; de Miranda, P.; King, D.H.; Page, D.A.; Longstreth, J.A.; Rocco, L. and Lietman, P.S.: Effects of probenecid on the pharmacokinetics and elimination of acyclovir in humans. Antimicrobial Agents and Chemotherapy 21: 804–807 (1982a).
Laskin, O.L.; Longstreth, J.A.; Saral, R.; de Miranda, P.; Keeney, R. and Lietman, P.S.: Pharmacokinetics and tolerance of acyclovir, a new anti-herpesvirus agent, in humans. Antimicrobial Agents and Chemotherapy 21: 393–398 (1982b).
Laskin, O.L.; Longstreth, J.A.; Whelton, A.; Krasny, H.C.; Keeney, R.E.; Rocco, L. and Lietman, P.S.: Effect of renal failure on the pharmacokinetics of acyclovir. Acyclovir Symposium. American Journal of Medicine 73: 197–201 (1982c).
Laskin, O.L.; Longstreth, J.A.; Whelton, A.; Rocco, L.; Lietman, P.S.; Krasny, H.C. and Keeney, R.E.: Acyclovir kinetics in end-stage renal disease. Clinical Pharmacology and Therapeutics 31: 594–601 (1982d).
Laskin, O.L.; Saral, R.; Burns, W.H.; Angelopulas, C.M.; Lietman, P.S.: Acyclovir concentrations and tolerance during repetitive administration for 18 days. Acyclovir Symposium. American Journal of Medicine 73: 221–224 (1982e).
Lass, J.H.; Pavan-Langston, D. and Park, N.: Acyclovir and corneal wound healing. American Journal of Ophthalmology 88: 102–108 (1979).
Lerner, A.M.: Acyclovir reaches clinical trial. Annals of Internal Medicine 96: 370–372 (1982).
Levin, M.J. and Leary, P.L.: Inhibition of human herpesviruses by combinations of acyclovir and human leukocyte interferon. Infection and Immunity 32: 995–999 (1981).
Levin, M.J.; Leary, P.L. and Arbeit, R.D.: Effect of acyclovir on the proliferation of human fibroblasts and peripheral blood mononuclear cells. Antimicrobial Agents and Chemotherapy 17: 947–953 (1980).
Lutwick, L.I.; Herbert, M.B. and Sklamberg, T.: In vitro activity of various DNA polymerase inhibitors against hepatitis B virus (HBV) DNA polymerase activity (DPA) [abstract]. 21st Interscience Conference on Antimicrobial Agents and Chemotherapy, Chicago, 4–6 November (1981).
Malewicz, B.; Momsen, M. and Jenkin, H.M.: Combined effect of acyclovir and amphotericin B on the replication of pseudorabies in BHK-21 cells. Antimicrobial Agents and Chemotherapy 23: 119–124 (1983).
Mar, E.; Patel, P.C.; Huang, E.: Effect of 9-(2-hydroxyethoxymethyl) guanine on viral-specific polypeptide synthesis in human cytomegalovirus-infected cells. Acyclovir Symposium.American Journal of Medicine 73: 82–85 (1982).
McCulley, J.P.; Binder, P.S.; Kaufman, H.E.; O’Day, D.M. and Poirier, R.H.: Double-blind, multicenter clinical trial of acyclovir vs idoxuridine for treatment of epithelial herpes simplex keratitis. Ophthalmology 89: 1195–1200 (1982).
McGill, J.: Topical acyclovir in herpes zoster ocular involvement. British Journal of Ophthalmology 65: 542–545 (1981).
McGill, J.; McDonald, D.R.; Fall, C.; McKendrick, G.D.W. and Copplestone, A.: Intravenous acyclovir in acute herpes zoster infection. Journal of Infection 6: 157–161 (1983).
McGill, J. and Tormey, P.: Use of acyclovir in herpetic ocular infection. Acyclovir Symposium. American Journal of Medicine 73: 286–289 (1982).
McGill, J.; Tormey, P. and Walker, C.B.: Comparative trials of acyclovir and adenine arabinoside in the treatment of herpes simplex corneal ulcers. British Journal of Ophthalmology 65: 610–613 (1981).
McGuirt, P.V. and Furman, P.A.: Acyclovir inhibition of viral DNA chain elongation in herpes simplex virus-infected cells. Acyclovir Symposium. American Journal of Medicine 73: 67–71 (1982).
McLaren, C.; Corey, L.; Sibrack, C.D. and Barry, D.W.: In vitro sensitivity of genital herpes simplex viruses isolated during acyclovir (ACV) therapy; in Kaplan et al. (Eds) International Workshop on Herpesviruses, Bologna, 27–31 July (1981), pp. 211–212 (Esculapio Publishing Company, Bologna 1981a).
McLaren, C.; Sibrack, C.D. and Barry, D.W.: Spectrum of sensitivity to acyclovir of herpes simplex virus clinical isolates. Acyclovir Symposium. American Journal of Medicine 73: 376–379 (1982).
McLaren, C.; Sibrack, C.D.; Corey, L; Meyers, J.; Saral, R.; Burns, W.H. and Barry, D.W.: Sensitivity of HSV isolates after clinical treatment with acyclovir (abstract). 21st Interscience Conference on Antimicrobial Agents and Chemotherapy, Chicago, 4–6 November (1981b).
Merigan, T.C.: Immunosuppression and herpesviruses; in Nahmias et al. (Eds) The Human Herpesvirus: An Interdisciplinary Prospective. Proceedings International Conference on Human Herpesviruses, Atlanta, 17–21 March (1980), pp. 308–316 (Elsevier, New York, 1981).
Mertz, G.J.; Reichman, R.; Dolin, R.; Richman, D.D.; Oxman, M.; Large, K.; Tyrrell, D.; Portnoy, J. and Corey, L.: Double blind placebo controlled trial of oral acyclovir for first episode genital herpes. 22nd Interscience Conference on Antimicrobial Agents and Chemotherapy, Florida, 4–6 October (1982).
Meyers, J.D.; Wade, J.C.; Mitchell, C.D.; Saral, R.; Lietman, P.S.; Durack, D.T.; Levin, M.J.; Segreti, A.C. and Balfour Jr, H.H.: Multicenter collaborative trial of intravenous acyclovir for treatment of mucocutaneous herpes simplex virus infection in the immunocompromised. Acyclovir Symposium. American Journal of Medicine 73: 229–235 (1982).
Miller, W.H. and Miller, R.L.: Phosphorylation of acyclovir (acycloguanosine) monophosphate by GMP kinase. Journal of Biological Chemistry 255: 7204–7207 (1980).
Mindel, A., Adler, M.W.; Sutherland, S. and Fiddian, A.P.: Intravenous acyclovir treatment for primary genital herpes. Lancet 1: 697–700 (1982a).
Mindel, A.; Adler, M.W.; Sutherland, S. and Fiddian, A.P.: Intravenous acyclovir in genital herpes. Acyclovir Symposium. American Journal of Medicine 73: 347–350 (1982b).
Mitchell, C.D.; Bean, B.; Gentry, S.R.; Groth, K.E.; Boen, J.R. and Balfour Jr, H.H.: Acyclovir therapy for mucocutaneous herpes simplex infections in immunocompromised patients. Lancet 1: 1389–1392 (1981).
Morgan, K.S.; Wander, A.H.; Kaufman, H.E.; Varnell, E.D. and Creagh-Kirk, T.: Toxicity and tolerance of 9-(2-hydroxyethoxymethyl) guanine. Chemotherapy 26: 405–408 (1980).
Moore, H.L.; Szczech, G.M.; Rodwell, D.E.; Kapp, R.W. Jr.; de Miranda, P. and Tucker, W.E. Jr: Lack of effect of acyclovir on reproduction and development of laboratory animals. Fundamental and Applied Toxicology (In press, 1983).
Moore, D.F.; Taylor, S.C and Bryson, Y.J.: Virus inhibition assay for measurement of acyclovir levels in human plasma and urine. Antimicrobial Agents and Chemotherapy 20: 787–792 (1981).
Myerson, D. and Hsiung, D.: Discordant sensitivity of herpes simplex virus strains to acyclovir in vitro and in vivo (abstract). American Society of Microbiologists, Atlanta, 7–12 March (1982).
Nahmias, A.; Kerrick, G.; Keyserling, H.L.; Davis, G.; Alexander, J.; Corey, L.; Hatcher, V.; Luby, J.; Mills, J. and Sacks, S.: Patient initiated therapy for recurrent genital herpes infections. Acyclovir Symposium. American Journal of Medicine 73: 342–346 (1982).
Nesburn, A.B.; Wiley, D.E. and Trousdale, M.D.: Effect of intensive acyclovir therapy during artificial reactivation of latent herpes simplex virus. Proceedings of the Society for Experimental Biology and Medicine 172: 316–323 (1983).
Nilsen, A.E.; Assen, T.; Halsos, A.M.; Kinge, B.R.; Tjøtta, E.A.L.; Wikström, K. and Fiddian, A.P.: Efficacy of oral acyclovir in the treatment of initial and recurrent genital herpes. Lancet 2: 571–573 (1982).
O’Brien, W.J.; Clough, D.W.; Geroski, D.H. and Edelhauser, H.F.: Effects of nucleoside antivirals and their metabolites on the corneal endothelium. Current Eye Research 1: 243–248 (1981).
O’Brien, W.J. and Taylor, J.L.: Chemotherapy of herpetic keratitis induced by acyclovir-resistant strains of herpes simplex virus type 1. Acyclovir Symposium. American Journal of Medicine 73: 294–299 (1982).
Offit, P.A.; Starr, S.E.; Zolnick, P. and Plotkin, S.A.: Acyclovir therapy in neonatal herpes simplex virus infection. Pediatric Infectious Disease 1: 253–255 (1982).
O’Meara, A. and Hillary, I.B.: Acyclovir in the management of herpes virus infections in immunosuppressed children. Irish Journal of Medical Science 150: 73–77 (1981).
Oosterhuis, J.A.; Versteeg, J.; Kruit, P.J. and Postma, B.H.: Acyclovir treatment in experimental herpetic keratitis in rabbits. Ophthalmic Research 12: 38–44 (1980).
Overall Jr, J.C.: Persistent problems with persistent herpes viruses. New England Journal of Medicine 305: 95–97 (1981a).
Overall Jr, J.C.: Antiviral chemotherapy of oral and genital herpes simplex infections; in Nahmias, A.J.; Dowdle, W.R. and Schinazi, R.I. (Eds) The Human Herpesvirus: an Interdisciplinary Prospective: Proceedings International Conference Human Herpesviruses, Atlanta, 17–21 March (1980), pp. 447–465 (Elsevier, New York 1981b).
Pagano, J.S. and Datta, A.K.: Perspectives on interactions of acyclovir with Epstein-Barr and other herpes viruses. Acyclovir Symposium. American Journal of Medicine 73: 18–26 (1982).
Pancic, F.; Steinberg, B.A.; Diana, G.D.; Carabateas, P.M.; Gorman, W.G. and Came, P.E.: Antiviral activity of Win 41258-3, a pyrazole compound against herpes simplex virus in mouse genital infection and in guinea pig skin infection. Antimicrobial Agents and Chemotherapy 19: 470–476 (1981).
Park, N.; Pavan-Langston, D. and De Clercq, E.: Effect of acyclovir, bromovinyldeoxyuridine, vidarabine, and L-lysine on latent herpes simplex virus in vitro. Acyclovir Symposium, American Journal of Medicine 73: 151–154 (1982b).
Park, N.; Pavan-Langston, D. and Hettinger, M.E.: Acyclovir therapy for the orofacial and ganglionic HSV infection in hairless mice. Journal of Dental Research 59: 2080–2086 (1980a).
Park, N.; Pavan-Langston, D.; Hettinger, M.E.; McLean, S.L.; Albert, D.M.; Lin, T. and Prusoff, W.H.: Topical therapeutic efficacy of 9-(2-hydroxyethoxymethyl) guanine and 5-iodo-5′-amino-2′,5′-dideoxyuridine on oral infection with herpes simplex virus in mice. Journal of Infectious Diseases 141: 575–579 (1980b).
Park, N.; Pavan-Langston, D. and McLean, S.L.: Acyclovir in oral and ganglionic herpes simplex virus infections. Journal of Infectious Diseases 140: 802–806 (1979a).
Park, N.; Pavan-Langston, D.; McLean, S.L. and Albert, D.M.: Therapy of experimental herpes simplex encephalitis with acyclovir in mice. Antimicrobial Agents and Chemotherapy 15: 775–779 (1979b).
Park, N.; Pavan-Langston, D.; McLean, S.L. and Lass, J.H.: Acyclovir topical therapy of cutaneous herpes simplex virus infection in guinea pigs. Archives of Dermatology 116: 672–675 (1980c).
Park, N.H.; Pavan-Langston, D.; Boisjoly, H.M. and De Clercq, E.: Chemotherapeutic efficacy of E-5-(2-bromovinyl)-2’-deoxyuridine for orofacial infection with herpes simplex virus type 1 in mice. Journal of Infectious Disease 145: 909–913 (1982a).
Parker, L.M.; Lipton, J.M.; Binder, N.; Crawford, E.L.; Kudisch, M. and Levin, M.J.: Effect of acyclovir and interferon on human hematopoietic progenitor cells. Antimicrobial Agents and Chemotherapy 21: 146–150 (1982).
Parris, D.S. and Harrington, J.E.: Herpes simplex virus variants resistant to high concentrations of acyclovir exist in clinical isolates. Antimicrobial Agents and Chemotherapy 22: 71–77 (1982).
Pavan-Langston, D.; Campbell, R. and Lass, J.: Acyclic antimetabolite therapy of experimental herpes simplex keratitis. American Journal of Ophthalmology 86: 618–623 (1978).
Pavan-Langston, D.; Lass, J.; Hettinger, M. and Udell, I.: Acyclovir and vidarabine in the treatment of ulcerative herpes simplex keratitis. American Journal of Ophthalmology 92: 829–835 (1981a).
Pavan-Langston, D.; Park, N. and Hettinger, M.: Ganglionic herpes simplex and systemic acyclovir. Archives of Ophthalmology 99: 1417–1419 (1981b).
Pavan-Langston, D.; Park, N. and Lass, J.H.: Herpetic ganglionic latency. Archives of Ophthalmology 97: 1508–1510 (1979).
Peterslund, N.A.; Seyer-Hansen, K.; Ipsen, J.; Esmann, V.; Schønheyder, H. and Juhl, H.: Acyclovir in herpes zoster. Lancet 2: 827–830 (1981).
Peyramond, D.; Denoyel, G.A.; Phillip, T.; Soillet, G.; Philippe, N.; Bertrand, J.L. and Bertoye, A.: Les infections à virus varicelle-zoster chez l’infant immunodéprimé. Archives Françaises de Pediatrie 40: 95–99 (1983).
Phillips, CF.: Cytomegalovirus vaccine: A realistic appraisal. Hospital Practice 14: 75–80 (1979).
Pizzo, P.A.: Infectious complications in the child with cancer. II. Management of specific infectious organisms. Journal of Pediatrics 98: 513–523 (1981).
Platt, M.P.W, and Eden, O.B.: Vasculitis in association with chickenpox treatment in childhood acute lymphoblastic leukemia. Lancet 2: 763–764 (1982).
Plotkin, S.A.; Starr, S.E. and Bryan, C.K.: In vitro and in vivo responses of cytomegalovirus to acyclovir. Acyclovir Symposium. American Journal of Medicine 73: 257–261 (1982).
Poirier, R.H.; Kingham, J.D.; Hutcherson, J.D.: Human aqueous penetration of topically applied acyclovir ophthalmic ointment, 3% (abstract). Acyclovir Symposium. American Journal of Medicine 73: 393 (1982).
Prentice, H.G. and Hann, I.M.: Prophylactic studies against herpes infections in severely immunocompromised patients with acyclovir. Journal of Infection 6(Suppl. I): 17–21 (1983).
Price, R.W.: Herpes zoster. An approach to systemic therapy. Medical Clinics of North America 66: 1105–1117 (1982).
Prober, C.G.; Kirk, L.E. and Keeney, R.E.: Acyclovir therapy of chickenpox in immunosuppressed children — A collaborative study. Journal of Pediatrics 101: 622–625 (1982).
Quinn, R.P.; de Miranda, P.; Gerald, L. and Good, S.S.: A sensitive radioimmunoassay for the antiviral BW2484 9-(2-hydroxyethoxymethyl)-guanine. Analytical Biochemistry 98: 319–328 (1979).
Quinn, R.P.; Wolberg, G.; Medzihradsky, J. and Elion, G.B.: Effect of acyclovir on various murine in vivo and in vitro immunologic assay systems. Acyclovir Symposium. American Journal of Medicine 73: 62–66 (1982).
Raimer, S.S. and Pursley, T.V.: Office management of viral skin infections in the elderly. Geriatrics 36: 53–63 (1981).
Reichman, R.C.; Badger, G.J.; Guinan, M.E.; Nahmias, A.J.; Keeney, R.E.; Davis, L.G.; Ashikaga, T. and Dolin, R.: Topically administered acyclovir in the treatment of recurrent herpes simplex genitalis: A controlled trial. Journal of Infectious Diseases 147: 336–340 (1983a).
Reichman, R.C.; Badger, G.J.; Mertz, G.J.; Corey, L.; Richman, D.; Oxman, M.; Connor, J.; Bryson, Y.; Tyrrell, D.; Portnoy, J. and Dolin, R.: Patient-initiated therapy of recurrent herpes simplex genitalis with orally administered acyclovir. Clinical Research 31: 373A (1983b).
Reichman, R.C.; Badger, G.J.; Richman, D.D.; Oxman, M.; Connor, J.; Mertz, G.J.; Corey, L.; Larson, T.; Bryson, Y.; Tyrrell, D.; Portnoy, J. and Dolin, J.: Treatment of recurrent herpes simplex genitalis with orally administered acyclovir. 22nd Interscience Conference on Antimicrobial Agents and Chemotherapy, Florida, 4–6 October (1982a).
Reichman, R.C.; Ginsberg, M.; Barrett-Connor, E.; Wyborny, C.; Connor, J.D.; Redfield, D.; Savoia, M.C.; Richman, D.D.; Oxman, M.N.; Dandliker, P.S.; Badger, G.J.; Ashikaga, T. and Dolin, R.: Controlled trial of acyclovir in the therapy of recurrent herpes simplex genitalis. Acyclovir Symposium. American Journal of Medicine 73: 338–341 (1982b).
Rollinson, E.A.: Acyclovir and equine rhinopneumonitis virus (EHV-1): Activity in vitro and efficacy against viral hepatitis in hamsters; in Kaplan et al. (Eds) International Workshop on Herpesviruses, Bologna, 27–31 July (1981), p. 206 (Esculapio Publishing Company, Bologna 1981).
Rose, R.M.; Crumpacker, C.S.; Waner, J. and Brain, J.D.: Treatment of murine cytomegalovirus pneumonia with acyclovir and interferon (abstract). American Review of Respiratory Disease 127: 198–202 (1983).
Salo, O.P.; Lassus, A.; Hovi, T. and Fiddian, A.P.: Double-blind, placebo-controlled, trial of oral acyclovir in recurrent genital herpes. European Journal of Sexually Transmitted Diseases (In press, 1983).
Saral, R.; Burns, W.H.; Laskin, O.L.; Santos, G.W. and Lietman, P.S.: Acyclovir prophylaxis of herpes-simplex-virus infections. A randomized, double-blind, controlled trial in bonemarrow-transplant recipients. New England Journal of Medicine 305: 63–67 (1981).
Schaeffer, H.J.: Acyclovir chemistry and spectrum of activity. Acyclovir Symposium. American Journal of Medicine 73: 4–6 (1982).
Schaeffer, H.J.; Beauchamp, L; de Miranda, P.; Elion, G.B.; Bauer, D.J. and Collins, P.: 9-(2-hydroxyethoxymethyl)-guanine activity against viruses of the herpes group. Nature 272: 583–585 (1978b).
Schinazi, R.F. and Nahmias, A.J.: Different in vitro effects of dual combinations of anti-herpes simplex virus compounds. Acyclovir Symposium. American Journal of Medicine 73: 40–48 (1982).
Schinazi, R.F.; Peters, J.; Chance, D.; Wickliffe, C.L. and Nahmias, A.J.: Treatment of herpes simplex virus encephalitis in mice with different antiviral and anti-inflammatory agents in combination; in Kaplan et al. (Eds) International Workshop on Herpesviruses, Bologna, 27–31 July (1981), p. 185 (Esculapio Publishing Company, Bologna 1981).
Schinazi, R.F.; Peters, J.; Williams, C.C.; Chance, D. and Nahmias, A.J.: Effects of combinations of acyclovir with vidarabine or its 5′-monophosphate on herpes simplex viruses in cell culture and in mice. Antimicrobial Agents and Chemotherapy 22: 499–507 (1982).
Schnipper, L.E. and Crumpacker, C.S.: Resistance of herpes simplex virus to acycloguanosine: Role of viral thymidine kinase and DNA polymerase loci. Proceedings of the National Academy of Science 77: 2270–2273 (1980).
Schnipper, L.E.; Crumpacker, C.S.; Marlowe, S.I.; Kowalsky, P.; Hershey, B.J. and Levin, M.J.: Drug-resistant herpes simplex virus in vitro and after acyclovir treatment in an immunocompromised patient. Acyclovir Symposium. American Journal of Medicine 73: 387–392 (1982).
Selby, P.J.; Powles, R.L.; Jameson, B.; Kay, H.E.M.; Watson, J.G.; Thornton, R.; Morgenstern, G.; Clink, H.M.; McElwain, T.J.; Prentice, H.G.; Corringham, R.; Ross, M.G.; Hoffbrand, A.V. and Brigden, D.: Parenteral acyclovir therapy for herpes Virus infections in man. Lancet 2: 1267–1270 (1979).
Serota, F.T.; Starr, S.E.; Bryan, C.K.; Koch, P.A.; Plotkin, S.A. and August, C.S.: Acyclovir treatment of herpes zoster infections. Use in children undergoing bone marrow transplant. Journal of the American Medical Association 247: 2132–2135 (1982).
Shigeta, S.; Yokota, T.; Iwabuchi, T.; Baba, M.; Konno, K.; Ogata, M. and De Clercq, E.: Comparative efficacy of antiherpes drugs against various strains of varicella zoster virus. Journal of Infectious Diseases 147: 576–584 (1983).
Shiota, H.: Clinical evaluation of acyclovir in the treatment of ulcerative herpetic keratitis. Acyclovir Symposium. American Journal of Medicine 73: 307–310 (1982).
Shiota, H.; Ogawa, T.; Yamane, S. and Tokushima: Studies of acyclovir and ara-AMP against herpetic keratitis in rabbits; in Sundmache, R. (Ed.) Herpetische Augenerkrankungen, pp. 315–318 (J.F. Bergmann Verlag, München 1981).
Shiota, H.; Sumiko, I. and Yamane, S.: Efficacy of acycloguanosine against herpetic ulcers in rabbit cornea. British Journal of Ophthalmology 63: 425–428 (1979).
Sibrack, C.D.; Gutman, L.T.; Wilbert, C.M.; McLaren, C. and Barry, D.W.: Altered pathogenicity of acyclovir (ACV) resistant HSV from an immunodeficient child (abstract). Pediatric Research 15: 621 (1981).
Sibrack, C.D.; McLaren, C. and Barry, D.W.: Disease and latency characteristics of clinical herpes simplex virus isolates after acyclovir therapy. Acyclovir Symposium. American Journal of Medicine 73: 372–375 (1982).
Sicher, S.E. and Oh, J.O.: Acyclovir therapy of neonatal herpes simplex virus type 2 infections in rabbits. Antimicrobial Agents and Chemotherapy 20: 503–507 (1981).
Skubitz, K.M.; Quinn, R.P. and Lietman, P.S.: Rapid acyclovir radioimmunoassay, using charcoal adsorption. Antimicrobial Agents and Chemotherapy 21: 352–354 (1982).
Smith, C.I.; Scullard, G.H.; Gregory, P.B.; Robinson, W.S. and Merigan, T.C: Preliminary studies of acyclovir in chronic hepatitis B. Acyclovir Symposium. American Journal of Medicine 73: 267–269 (1982).
Smith, K.O.; Kennell, W.L.; Poirier, R.H. and Lynd, F.T.: in vitro and in vivo resistance of herpes simplex virus to 9-(2-hydroxyethoxymethyl) guanine (acycloguanosine). Antimicrobial Agents and Chemotherapy 17: 144–150 (1980).
Soike, K.F. and Gerone, P.J.: Acyclovir in the treatment of simian varicella virus infection of the African green monkey. Acyclovir Symposium. American Journal of Medicine 73: 112–117 (1982).
Soike, K.F.; Felsenfeld, A.D. and Gerone, P.J.: Acyclovir treatment of experimental simian varicella infection of monkeys. Antimicrobial Agents and Chemotherapy 20: 291–297 (1981).
Spector, S.A.; Connor, J.D.; Hintz, M.; Quinn, R.P.; Blum, M.R. and Keeney, R.E.: Single dose pharmacokinetics of acyclovir. Antimicrobial Agents and Chemotherapy 19: 608–612 (1981).
Spector, S.A.; Hintz, M.; Wyborny, C.; Connor, J.D.; Keeney, R.E. and Liao, S.: Treatment of herpes virus infections in immunocompromised patients with acyclovir by continuous intravenous infusion. Acyclovir Symposium. American Journal of Medicine 73: 275–280 (1982a).
Spector, S.A.; Tyndall, M. and Kelley, E.: Effects of acyclovir combined with other antiviral agents on human cytomegalovirus. Acyclovir Symposium. American Journal of Medicine 73: 36–39 (1982b).
Spruance, S.L. and Crumpacker, C.S.: Topical 5 percent acyclovir in polyethylene glycol for herpes simplex labialis. Antiviral effect without clinical benefit. Acyclovir Symposium. American Journal of Medicine 73: 315–318 (1982).
Spruance, S.L.; Crumpacker, C.S.; Schnipper, L.E.; Kern, E.R.; Marlow, S.; Arndt, K.A. and Overall, Jr J.C.: Topical 10% acyclovir (ACV) in polyethylene glycol (PEG) for herpes simplex labialis: Results of treatment begun in the prodrome or erythema stages (abstract). 22nd Interscience Conference on Antimicrobial Agents and Chemotherapy, Florida 4–6 October (1982).
Spruance, S.L. and Krueger, G.G.: Effect of topical acyclovir on epidermal wound healing in pigs (abstract). Clinical Research 29: 82A (1981).
Stanwick, T.L.; Schinazi, R.F.; Campbell, D.E. and Nahmias, A.: Combined antiviral effect of interferon and acyclovir on herpes simplex virus types 1 and 2. Antimicrobial Agents and Chemotherapy 19: 672–674 (1981).
St Clair, M.H.; Furman, P.A.; Biron, K.K. and Elion, G.B.: Inhibition of several virally induced DNA polymerases by the triphosphate of 9-(2-hydroxyethoxymethyl) guanine; in Nelson, J.D. and Grassi, C. (Eds) Current Chemotherapy and Infectious Disease: Proceedings of the 11th International Congress of Chemotherapy and the 19th Interscience Conference on Antimicrobial Agents and Chemotherapy, Boston, 1–5 October (1979), Vol. II, pp. 1380–1381 (American Society for Microbiology, Washington DC 1980a).
St Clair, M.H.; Furman, P.A.; Lubbers, CM. and Elion, G.B.: Inhibition of cellular α and virally induced deoxyribonucleic acid polymerases by the triphosphate of acyclovir. Antimicrobial Agents and Chemotherapy 18: 741–745 (1980b).
Steele, R.W.; Marmer, D.J. and Keeney, R.E.: Comparative in vitro immunotoxicity of acyclovir and other antiviral agents. Infection and Immunity 28: 957–962 (1980).
Steele, R.W.; Keeney, R.E.; Bradsher, R.W.; Moses, E.B. and Soloff, B.L.: Treatment of varicella zoster meningoencephalitis with acyclovir-demonstration of virus in cerebrospinal fluid by electron microscopy. American Journal of Clinical Pathology 80: 57–60 (1983).
Straus, S.; Seidlin, M.; Takiff, H.; Bachrach, S.; DiGiovanna, J.; Western, K.; Creagh-Kirk, T.; Lininger, L. and Ailing, D.: Suppression of recurrent genital herpes with oral acyclovir. Clinical Research 31: 543A (1983).
Straus, S.E.; Smith, H.A.; Brickman, C.; de Miranda, P.; McLaren, C. and Keeney, R.E.: Acyclovir for chronic mucocutaneous herpes simplex virus infection in immunosuppressed patients. Annals of Internal Medicine 96: 270–277 (1982).
Sullivan, J.L.; Baker, S.M.; Byron, K.S.; Brewster, F.E. and Sairenji, T.: Failure of acyclovir to inhibit polyclonal Epstein-Barr virus induced lymphoproliferation in the immunocompromised host. Clinical Research 30: 698A (1982b).
Sullivan, J.L.; Byron, K.S.; Brewster, F.E.; Sakamoto, K.; Shaw, J.E. and Pagano, J.S.: Treatment of life-threatening EpsteinBarr virus infections with acyclovir. Acyclovir Symposium, American Journal of Medicine 73: 262–266 (1982a).
Swart, R.N.J.; Vermeer, B.J.; van der Meer, J.W.M.; Enschedé, A.J. and Versteeg, J.: Treatment of eczema herpeticum with acyclovir. Archives of Dermatology 119: 13–16 (1983).
Teare, E.L. and Clements, M.R.: Acyclovir for suspected systemic herpes infections. Lancet 1: 42 (1980).
Thin, R.N.; Nabarro, J.M.; Parker, J.D. and Fiddian, A.P.: Topical acyclovir in the treatment of initial genital herpes. British Journal of Venereal Diseases 59: 116–119 (1983).
Tormey, P.; McGill, J. and Walker, C.: Use of acyclovir in herpes simplex corneal ulcers. Transactions of the Ophthalmological Societies of the United Kingdom 101: 6–8 (1981).
Trousdale, M.D.; Dunkel, E.C. and Nesburn, A.B.: Effect of acyclovir on acute and latent herpes simplex virus infections in the rabbit. Investigative Ophthalmology and Visual Science 19: 1336–1341 (1980).
Trousdale, M.D. and Nesburn, A.B.: Evaluation of the antiherpetic activity of acyclovir in rabbits. Acyclovir Symposium. American Journal of Medicine 73: 155–160 (1982).
Trousdale, M.D.; Nesburn, A.B. and Miller, C.A.: Assessment of acyclovir on acute ocular infection induced by drug-resistant strains of HSV-1. Investigative Ophthalmology and Visual Science 20: 230–235 (1981).
Trousdale, M.D.; Nesburn, A.B.; Su, T.; Lopez, C.; Watanabe, K.A. and Fox, J.J.: Activity of l-(2’-flouro-2’-deoxy-β-d-ara-binofuranosyl) thymine against herpes simplex virus in cell cultures and rabbit eyes. Antimicrobial Agents and Chemotherapy 23: 808–813 (1983).
Tucker, W.E.: Preclinical toxicity profile of acyclovir: An overview. Acyclovir Symposium. American Journal of Medicine 73: 27–30 (1982).
Tucker, W.E. Jr; Macklin, A.W.; Szot, R.J.; Johnson, R.E.; Elion, G.B.; de Miranda, P. and Szczech, G.M.: Preclinical toxicology studies with acyclovir: Acute and subchronic studies. Fundamental and Applied Toxicology (In press, 1983b).
Tucker, W.E. Jr; Krasney, H.C., de Miranda, P.; Goldenthal, E.I., Elion, G.B.; Hajian, G. and Szczech, G.M.: Preclinical toxicology studies with acyclovir: Carcinogenicity bioassays and chronic toxicity tests. Fundamental and Applied Toxicology (In press 1983a).
Tyms, A.S.; Seamans, E.M. and Naims, H.M.: in vitro activity of acyclovir and related compounds against cytomegalovirus infections. Journal of Antimicrobial Chemotherapy 8: 65–72 (1981).
Van der Meer, J.W.M. and Versteeg, J.: Acyclovir in severe herpes virus infections. Acyclovir Symposium. American Journal of Medicine 73: 271–275 (1982).
Van Dyke, R.B.; Connor, J.B.; Wyborny, C.; Hintz, C. and Keeney, R.E.: Pharmacokinetics of orally administered acyclovir in patients with herpes progenitalis. Acyclovir Symposium. American Journal of Medicine 73: 172–175 (1982a).
Van Dyke, R.; Straube, R.; Large, K.; Hintz, M.; Spector, S. and Connor, J.D.: Pharmacokinetics of increased dose oral acyclovir (abstract). 22nd Interscience Conference on Antimicrobial Agents and Chemotherapy, Florida, 4–6 October (1982b).
Van Ekdom, L.T.S. and Versteeg, J.: Preventive and curative effects of acyclovir on central nervous system infections in hamster inoculated with herpes simplex virus. Acyclovir Symposium. American Journal of Medicine 73: 161–164 (1982).
Van Ganswijk, R.; Oosterhuis, J.A.; Swart-Van den Berg, M. and Versteeg, J.: Acyclovir treatment in stromal herpetic keratitis. Documenta Ophthalmologica 55: 57–61 (1983).
Van Vloten, W.A.; Swart, R.N.J. and Pot, F.: Topical acyclovir therapy in patients with recurrent orofacial herpes simplex infections (Unpublished data on file, Burroughs Wellcome Co.).
Van Weel-Sipman, M.H.; Van der Meer, J.W.M.; de Koning, J. and Versteeg, J.: Severe atypical recurrent varicella in childhood leukaemia. Lancet 1: 147–148 (1981).
Von Schulthess, G.K. and Sauter, C.: Acyclovir and herpes zoster. New England Journal of Medicine 305: 1349 (1981).
Wade, J.C.; Day, L.; Crowley, J. and Meyers, J.D.: Suppression of the lymphocyte transformation response (LTR) to herpes simplex virus (HSV) by acyclovir (ACV) treatment after marrow transplant (abstract). Clinical Research 30: 425A (1982c).
Wade, J.C.; Hintz, M.; McGuffin, R.W.; Springmeyer, S.C.; Connor, J.D. and Meyers, J.D.: Treatment of cytomegalovirus pneumonia with high-dose acyclovir. Acyclovir Symposium. American Journal of Medicine 73: 249–255 (1982a).
Wade, J.C. and Meyers, J.D.: Neurological symptoms associated with parenteral acyclovir treatment after marrow transplantation. Annals of Internal Medicine 98: 921–925 (1983).
Wade, J.C.; Newton, B.; McLaren, C.; Flournoy, N.; Keeney, R.E. and Meyers, J.D.: Intravenous acyclovir to treat mucocutaneous herpes simplex virus infection after marrow transplantation. Annals of Internal Medicine 96: 265–269 (1982b).
Weinmaster, G.A.; Misra, V.; McGuire, R.; Babiuk, L.A. and De Clercq, E.: Bovid herpesvirus type-1 (infectious bovine rhinotracheitis virus)-induced thymidine kinase. Virology 118: 191–201 (1982).
Weller, I.V.D.; Carreno, V.; Fowler, V.; Monjardino, M.J.F.; Makinen, D.; Thomas, H.C. and Sherlock, S.: Acyclovir inhibits hepatitis B virus replication in man. Lancet 1: 273 (1982).
Weller, I.V.D.; Carreno, V.; Fowler, M.J.F.; Monjardino, J.; Makinen, D.; Varghese, Z.; Sweny, P.; Thomas, H.C. and Sherlock, S.: Acyclovir in hepatitis B antigen-positive chronic liver disease: Inhibition of viral replication and transient renal impairment with IV bolus administration. Journal of Antimicrobial Chemotherapy 11: 223–231 (1983).
Whitley, R.; Barton, N.; Collins, E.; Whelchel, J. and Diethelm, A.G.: Mucocutaneous herpes simplex virus infections in immunocompromised patients. A model for evaluation of topical antiviral agents. Acyclovir Symposium. American Journal of Medicine 73: 236–240 (1982a).
Whitley, R.J.; Blum, M.R.; Barton, N. and de Miranda, P.: Pharmacokinetics of acyclovir in humans following intravenous administration. Acyclovir Symposium. American Journal of Medicine 73: 165–170 (1982b).
Wildenhoff, K.E.; Esmann, V.; Ipsen, J.; Harving, H.; Peterslund, N.A. and Schønheyder, H.: Treatment of trigeminal and thoracic zoster with idoxuridine. Scandinavian Journal of Infectious Diseases 13: 257–262 (1981).
Wildenhoff, K.E.; Ipsen, J.; Esmann, V.; Ingemann-Jensen, H. and Poulsen, J.H.: Treatment of herpes zoster with idoxuridine ointment, including a multivariate analysis of symptoms and signs. Scand. J. Infect. Dis. 11: 1–9 (1979).
Wilhelmus, K.R.; Coster, DJ. and Jones, B.R.: Acyclovir and debridement in the treatment of ulcerative herpetic keratitis. American Journal of Ophthalmology 91: 323–327 (1981).
Wingard, J.R.; Stuart, R.K.; Saral, R. and Burns, W.H.: Activity of trifluorothymidine against cytomegalovirus. Antimicrobial Agents and Chemotherapy 20: 286–290 (1981).
Yeager, A.S.: Use of acyclovir in premature and term neonates. Acyclovir Symposium. American Journal of Medicine 73: 205–209 (1982).
Young, B.; Patterson, A. and Ravenscroft, T.: Double-blind clinical trial of acyclovir and adenine arabinoside in herpetic corneal ulceration. Acyclovir Symposium. American Journal of Medicine 73: 311–312 (1982a).
Young, B.J.; Patterson, A. and Ravenscroft, T.: Randomized double-blind clinical trial of acyclovir (Zovirax) and adenine arabinoside in herpes simplex corneal ulceration. British Journal of Ophthalmology 66: 361–363 (1982b).
Young, L.S.: Infection in the compromised host. Hospital Practice 16: 73–84 (1981).
Author information
Authors and Affiliations
Additional information
Various sections of the manuscript reviewed by: T. Chang, Faculty of Medicine, Tufts University School of Medicine, Boston, Massachusetts, USA; L.M.T. Collum, Corneal Clinic, Royal Victoria Eye and Ear Hospital, Dublin, Ireland; C. Crumpacker, Infectious Disease Division, Beth Israel Hospital, Boston, Massachusetts, USA; E. DeClercq, Rega Institute for Medical Research, Katholieke Universiteit Leuven, Leuven, Belgium; H.J. Field, Division of Virology, Addenbrooke’s Hospital, Cambridge, England; G.J. Galasso, Microbiology and Infectious Disease Program, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland, USA; O.L. Laskin, Faculty of Medicine and Pharmacology, New York Hospital-Cornell Medical Center, New York, USA; A.J. Nahmias, Department of Pediatrics and Division of Infectious Diseases and Immunology, Emory University School of Medicine, Atlanta, Georgia, USA; D. Pavan-Langston, Faculty of Ophthalmology, Harvard Medical School, Boston, Massachusetts, USA; N.A. Peterslund, Department of Internal Medicine and Infectious Diseases, Marselisborg Hospital, Denmark; J.J. Sanitato, Department of Ophthalmology, Louisiana State University Medical Center, New Orleans, Louisiana, USA; R.J. Schinazi, Department of Pediatrics and Division of Infectious Diseases and Immunology, Emory University School of Medicine, Atlanta, Georgia, USA; S.A. Spector, Division of Infectious Diseases and Department of Pediatrics, University of California Medical Center, San Diego, California, USA; R.J. Whitley, Department of Pediatrics, School of Medicine, University of Alabama in Birmingham, Birmingham, Alabama, USA.
‘Zovirax’ (Burroughs Wellcome).
Rights and permissions
About this article
Cite this article
Richards, D.M., Carmine, A.A., Brogden, R.N. et al. Acyclovir. Drugs 26, 378–438 (1983). https://doi.org/10.2165/00003495-198326050-00002
Published:
Issue Date:
DOI: https://doi.org/10.2165/00003495-198326050-00002