J Infect Dis. 1998 Aug;178(2):297-303.
Phenotypic and genotypic characterization of acyclovir-resistant herpes simplex viruses from immunocompromised patients.

Gaudreau A, Hill E, Balfour HH Jr, Erice A, Boivin G.

Division of Microbiology, Centre Hospitalier Universitaire de Quebec and Laval University, Quebec City, Canada.

Phenotypic and genotypic analyses were done on 30 acyclovir-resistant and 5 acyclovir-susceptible herpes simplex virus (HSV) isolates (22 HSV type 1 and 13 HSV type 2) recovered from 24 subjects. All isolates were susceptible to foscarnet. The phenotypes of the acyclovir-resistant HSV isolates were as follows: 17 were thymidine kinase (TK) deficient, 12 had decreased TK activity (produced low amounts of viral TK) or TK with altered substrate specificity, and 1 was undetermined. Sequencing analysis of the HSV TK gene revealed that 14 (46.7%) of 30 acyclovir-resistant isolates had an insertion or deletion of 1 or 2 nucleotides, especially in homopolymer runs of Gs, Cs, and rarely in As. On the other hand, 16 (53.3%) of 30 acyclovir-resistant isolates had point mutations in conserved or nonconserved regions of the TK gene. In conclusion, HSV can develop multiple strategies to exhibit acyclovir resistance, including, in about half of the cases, frameshift mutations in homopolymer nucleotide stretches of the TK gene.

Online pharmacy ref source - acyclovir: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9697707&dopt=Abstract acyclovir Zovirax




Int J Infect Dis. 1998 Jan-Mar;2(3):147-51.
Varicella pneumonitis: clinical presentation and experience with acyclovir treatment in immunocompetent adults.

El-Daher N, Magnussen R, Betts RF.

Department of Medicine, Infectious Diseases Unit, St. Mary's Hospital, Rochester, New York 14611, USA.

OBJECTIVE: Cases of varicella pneumonitis were reviewed to examine the effects of acyclovir therapy on outcome. METHODS: A retrospective chart review was done of all admissions of adults to two hospitals, between 1985 and 1995, because of complications of chickenpox. RESULTS: Fifteen patients were hospitalized for varicella pneumonitis during this period. No patient had a history of chickenpox as a child; all had a recent history (within 2-4 weeks prior to admission) of exposure to chickenpox in their family or neighborhood and developed respiratory symptoms 1 to 4 days after the appearance of the rash. Twelve patients (80%) had a history of cigarette smoking, and seven patients had a platelet count below the normal range. All patients were treated with intravenous acyclovir within 24 hours of admission, and all but one survived and were discharged from the hospital without comorbid conditions. The one mortality was attributed to bacterial superinfection. CONCLUSIONS: Acyclovir treatment may be of benefit for varicella pneumonitis, but no controlled trial has been performed to definitively answer this question.

Online pharmacy ref source - acyclovir: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9531661&dopt=Abstract acyclovir Zovirax




Enferm Infecc Microbiol Clin. 1999 Oct;17(8):390-3.
[Acyclovir may modulate clonal expansion of cd8+ lymphocytes induced by the Cytomegalovirus antigen]

[Article in Spanish]

Gavilan F, Caballero J, Cardenas M, Moreno J, Martinez L, Gallego C, Sanchez-Guijo P, Torre-Cisneros J.

Seccion de Enfermedades Infecciosas, Hospital Universitario Reina Sofia, Cordoba.

BACKGROUND: Although the potent antiviral effect of acyclovir on the Herpes-simplex (HSV) and Varicela-zoster (VZV) virus and the scarce effectiveness versus Cytomegalovirus (CMV) is known, some data suggest that it may have an immunodulator implicated in the control of these viral disease. The aim of this study was to characterize this possible effect of acyclovir versus the CMV antigen. METHODS: We stimulated cultures of mononuclear cells obtained in 7 healthy patients who were seropositive for CMV and HSV with CMV antigen, HSV and with phitohemaglutinine (PHA). The proliferation index and culture cell phenotype were later determined in the absence and presence of acyclovir (2 micrograms/ml). In another group the proliferation index and cell phenotype following stimulation with the CMV antigen were studied prior to and after treating the same volunteers with acyclovir for one week (800 mg/6h). RESULTS: The CMV antigen and HSV induced T cell proliferation predominantly involving the CD8+ subpopulation leading to an inversion of the CD4/CD8 quotient. On addition of acyclovir to the cell culture a moderate reduction was produced in lymphoproliferative response versus the CMV antigen and HVS, characteristically modulating CD8+ cell proliferation, thereby leading to reestablishment of the CD4/CD8 quotient. However, the proliferation induced by PHA was not inhibited. These results were produced on oral administration of acyclovir. CONCLUSIONS: Acyclovir modulates the lymphoproliferative response induced by CMV antigen. Based on this observation, the authors hypothesize that this immunomodulation may be related to its preventive effect on CMV disease in transplanted patients.

Online pharmacy ref source - acyclovir: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10563086&dopt=Abstract acyclovir Zovirax




Eur J Pharm Biopharm. 1998 Nov;46(3):285-91.
Acyclovir serum concentrations following peroral administration of magnetic depot tablets and the influence of extracorporal magnets to control gastrointestinal transit.

Groning R, Berntgen M, Georgarakis M.

Institute for Pharmaceutical Technology, University of Munster, M unster, Germany.

In the present investigations peroral acyclovir depot tablets with internal magnets were developed. An extracorporal magnet was used to prolong the gastric residence times of the dosage forms and to influence the duration of absorption of acyclovir. The magnetic depot tablets contained 200 mg acyclovir. In a three-way cross-over in vivo study with five healthy male subjects, the plasma concentration-time profiles of acyclovir were determined. The acyclovir plasma concentrations following peroral administration of magnetic depot tablets in the presence and absence of an extracorporal magnet were determined. A commercially available immediate release preparation was used as a reference preparation. In the presence of an extracorporal magnet which was placed in the stomach region, the plasma concentrations of acyclovir were significantly higher after 7, 8, 10 and 12 h (P<0.05, U-test, Wilcoxon, Mann-Whitney). The mean area under the plasma concentration-time-curve (AUC0-24h), in the presence of the extracorporal magnet was 2802.7 ngh/ml. Without the extracorporal magnet a mean AUC0-24h of 1598.8 ngh/ml was achieved. Computer simulations were carried out to show the influence of the gastric residence time of acyclovir depot preparations on the plasma concentration-time profiles of acyclovir. Copyright 1998 Elsevier Science B.V.

Online pharmacy ref source - acyclovir: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9885300&dopt=Abstract acyclovir Zovirax




J Dermatol Sci. 1996 Dec;13(3):237-41.
Efficacy of Cafon gel on cutaneous infection with herpes simplex virus (HSV)-2 and acyclovir-resistant HSV in mice.

Yoshida Y, Yamamura J, Sato H, Koyasu M, Obara Y, Sekiguchi H, Kawana T, Shiraki K.

Department of Virology, Toyama Medical and Pharmaceutical University, Japan.

Caffeine is known to inhibit replication of herpes simplex virus (HSV)-1 and the therapeutic efficacy of caffeine (Cafon) gel has been shown in a mouse model cutaneously infected with HSV-1. In this study we examined the inhibitory effect of caffeine on infection with HSV-2 and acyclovir-resistant HSV-1 strains, thymidine kinase (TK)-deficient and phosphonoacetic acid (PAA)-resistant HSV-1 in vitro and in vivo. Caffeine inhibited plaque formation of HSV-2 and acyclovir-resistant HSV-1 strains and their EC50 values ranged from 0.42 to 1.11 mg/ml. Topical treatment with Cafon gel was significantly effective in retarding the development of skin lesions caused by cutaneous infection with HSV-2 and PAA-resistant HSV-1 and in reducing the virus yield of the skin infected with TK-deficient HSV-1. The results suggested that Cafon gel would be useful for the topical treatment of cutaneous infection with HSV-2 and acyclovir-resistant HSV strains.

Online pharmacy ref source - acyclovir: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9023706&dopt=Abstract acyclovir Zovirax