J Infect Dis. 2000 Jun;181(6):2055-8. Epub 2000 Jun 05.
Resistance to antiviral drugs in herpes simplex virus infections among allogeneic stem cell transplant recipients: risk factors and prognostic significance.

Chakrabarti S, Pillay D, Ratcliffe D, Cane PA, Collingham KE, Milligan DW.

Department of Haematology, Birmingham Heartlands Hospital, Birmingham, United Kingdom.

Herpes simplex virus (HSV) infections in 75 allogeneic stem cell transplant recipients were analyzed. Sixteen patients developed HSV disease following transplantation. The risk factors were age, sex (females), unrelated donor graft, and graft-versus-host disease (GVHD) grade >/=2. Seven patients did not respond to acyclovir, and 3 patients failed to respond to foscarnet. Isolates from 4 patients developed resistance to acyclovir/penciclovir, and 3 patients had foscarnet-resistant isolates. The remaining 3 patients failed to respond to acyclovir, despite having sensitive isolates. All the isolates were sensitive to cidofovir, for which the IC(50) values correlated inversely with those for acyclovir (P=.01). The risk factors for clinical resistance to antiviral drugs were a GVHD grade >/=2 (P=.001) and the lack of ganciclovir prophylaxis (P=.01), with a higher nonrelapse mortality in the latter group (P<.0001). Clinical as well as in vitro resistance to antiviral drugs is common in patients with severe GVHD and is associated with a poor outcome.

Online pharmacy ref source - acyclovir: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10837192&dopt=Abstract acyclovir Zovirax




Antiviral Res. 1995 Jun;27(3):271-9.
Inhibitory action of acyclovir (ACV) and penciclovir (PCV) on plaque formation and partial cross-resistance of ACV-resistant varicella-zoster virus to PCV.

Hasegawa T, Kurokawa M, Yukawa TA, Horii M, Shiraki K.

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

Penciclovir has potent antiviral activity against varicella-zoster virus (VZV). We have characterized the inhibitory effects of penciclovir and acyclovir on the plaque formation of cell-free VZV and cross-resistance of acyclovir-resistant VZV to penciclovir. The apparent effective concentration for 50% plaque reduction (EC50) of penciclovir determined on the third day was significantly lower than that determined on the fourth or fifth day. The size of plaques was smaller in the presence of penciclovir than in the presence of acyclovir. The effective concentrations for 50% reduction of the number of infected cells per plaque were 1.40 and 5.00 micrograms/ml for penciclovir and acyclovir, respectively. Thus penciclovir suppressed spread of infection within developing plaques more efficiently than acyclovir. Five acyclovir-resistant VZV strains with altered DNA polymerase selected by acyclovir were examined for cross-resistance to penciclovir. They were 11- to 18-fold more resistant to ACV than the parent strain, but only 4- to 5-fold more resistant to PCV. Penciclovir-triphosphate carrying the 3'-hydroxyl group of 2'-deoxyribose might have better affinity to the altered viral DNA polymerase than acyclovir-triphosphate without the 3'-hydroxyl group.

Online pharmacy ref source - acyclovir: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8540749&dopt=Abstract acyclovir Zovirax




Invest Ophthalmol Vis Sci. 1993 Nov;34(12):3459-65.
Prophylactic acyclovir effectively reduces herpes simplex virus type 1 reactivation after exposure of latently infected mice to ultraviolet B.

Blatt AN, Laycock KA, Brady RH, Traynor P, Krogstad DJ, Pepose JS.

Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, MO 63110.

PURPOSE. To determine the potential efficacy and anatomic sites of action of prophylactic oral acyclovir using a murine model of ultraviolet-B-induced reactivation of herpes simplex 1 keratitis. METHODS. Latent infection with herpes simplex 1 (McKrae) was established in 80 National Institutes of Health inbred strain of mice. Forty of the mice were given acyclovir orally and the other 40 latently infected mice served as controls. Mice were exposed to 250 mJ/cm2 of ultraviolet-B radiation and killed on days 1, 2, 3, and 4 after ultraviolet-B radiation. Trigeminal ganglia and eyes from these mice were homogenized and incubated on Vero cell monolayers for recovery of reactivated virus. RESULTS. Based on the recovery of infectious virus after ultraviolet-B in treated versus control groups, acyclovir effectively reduced detectable viral reactivation at both the ocular level (P = 0.003) and the ganglionic level (P = 0.025). The numbers of viral culture-positive eye and trigeminal ganglia homogenates in the control group were 11 and 6 out of 40, respectively, compared to 1 and 0 out of 40 culture-positive eye and trigeminal ganglia homogenates in the acyclovir treated mice. Therapeutic serum levels of acyclovir were confirmed by high performance liquid chromatography. In the acyclovir-tested group, the single case of viral break-through at the ocular surface was not an acyclovir-resistant mutant. CONCLUSION. Prophylactic acyclovir effectively reduces the incidence of herpes simplex virus-1 reactivation after ultraviolet-B-induced reactivation in National Institutes of Health inbred strain of mice.

Online pharmacy ref source - acyclovir: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8225880&dopt=Abstract acyclovir Zovirax




Invest Ophthalmol Vis Sci. 1999 Feb;40(2):378-84.
Comparative antiviral efficacies of cidofovir, trifluridine, and acyclovir in the HSV-1 rabbit keratitis model.

Romanowski EG, Bartels SP, Gordon YJ.

Department of Ophthalmology, University of Pittsburgh School of Medicine, Pennsylvania, USA.

PURPOSE: To determine the relative antiviral inhibitory activity of topical 1% and 0.5% cidofovir, topical trifluridine (Viroptic; Burroughs-Wellcome, Research Triangle Park, NC), and topical acyclovir (Zovirax; The Wellcome Foundation, London, UK) during a 7-day period for the treatment of herpes simplex virus type 1 (HSV-1) keratitis and HSV-1 replication in the New Zealand rabbit ocular model. METHODS: In a series of four experiments using a two-eye design, a total of 80 New Zealand rabbits were inoculated in both eyes with HSV-1 McKrae after epithelial scarification. Forty-eight hours after inoculation, the rabbits were randomly assigned to a treatment group. Five treatment groups (16 rabbits/group) were evaluated: I, 1% cidofovir, twice daily for 7 days; II, 0.5% cidofovir, twice daily for 7 days; III, 3% acyclovir ointment, five times daily for 7 days; IV, 1% trifluridine, nine times daily for 3 days, then 4 times daily for 4 days; and V, control vehicle twice daily for 7 days. HSV-1 dendritic keratitis was graded in a masked fashion by slit-lamp examination on days 2, 3, 5, 7, 9, 11, and 14. Ocular viral cultures were obtained after slit-lamp examination on days 1, 3, 5, 7, 9, 11, and 14. RESULTS: Compared with the control group, all four treatment groups demonstrated significantly lower viral titers, fewer HSV-1-positive eyes/total during the treatment period, lower keratitis scores, fewer eyes with keratitis/total, and a shorter time to resolution of keratitis. Within the treatment groups, the 1% and 0.5% cidofovir treatments were significantly more effective than acyclovir and trifluridine as measured by the previous viral and keratitis parameters. CONCLUSIONS: Topical 1% and 0.5% cidofovir both appeared to be significantly more efficacious than topical trifluridine and acyclovir, during a 7-day course, in the treatment of experimental HSV-1 ocular disease in the New Zealand rabbit keratitis model.

Online pharmacy ref source - acyclovir: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9950596&dopt=Abstract acyclovir Zovirax




Int J Dermatol. 1997 Jun;36(6):457-9.
Cost-benefit of oral acyclovir in the treatment of herpes zoster.

Kubeyinje EP.

Skin Clinic, Arar Central Hospital, Saudi Arabia.

BACKGROUND: Oral acyclovir is a costly antiviral agent shown to be effective in the treatment of herpes zoster. Herpes zoster runs a relatively benign course in young, healthy individuals, as compared with elderly and immunologically compromised patients, in whom complications are common. This study attempts to assess the cost-benefit of treatment with oral acyclovir in young healthy adults with herpes zoster. PATIENTS AND METHODS: The records of 42 healthy young adults suffering from herpes zoster and treated with oral acyclovir (800 mg five times daily for 7 days) were compared with those of 40 healthy young adults with herpes zoster seen during the same period but treated without oral acyclovir. The duration of zoster-associated pain and the presence of complications were noted. RESULTS: There was no statistically significant difference in the duration of zoster-associated pain between the two groups of patients (P = 0.11). Other complications of herpes zoster were few and similar in the two groups. CONCLUSIONS: At a cost of $250 to $300 for a 7-day course of oral acyclovir, the use of this antiviral agent in healthy young individuals with herpes zoster is not justified, especially in developing countries with limited resources.

Online pharmacy ref source - acyclovir: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9248895&dopt=Abstract acyclovir Zovirax