welchlink.welch.jhu.edu

The aim of this study was to evaluate the association between acyclovir use and survival in HIV-infected patients. To achieve this, we used survival analysis in an observational cohort of HIV-infected patients enrolled in primary care at an urban HIV clinic. We measured survival in a cohort of HIV-infected patients who had CD4 cell counts < or = 500/mm3 and who enrolled for care at a single urban HIV clinic between December 1988 and April 1995. We compared survival in users of acyclovir alone, zidovudine alone, and acyclovir and zidovudine in combination with the survival of those using neither drug. Factors associated with improved survival were identified using Cox proportional hazards analysis. Among the 1408 patients enrolled, there were no significant differences in overall survival between acyclovir users and non-users. After adjustment for CD4 cell count, the use of other antiretroviral agents, race, transmission risk and a history of herpesvirus infection, acyclovir use alone was independently associated with a relative hazard (RH) of death of 1.008 (P = 0.969); zidovudine use alone with a RH of 0.559 (P < 0.001); and combination use of acyclovir and zidovudine associated with a RH of 1.062 (P = 0.788). Therefore we conclude that the use of acyclovir is not associated with prolonged survival in this cohort of HIV-infected patients.

Online pharmacy ref source - acyclovir: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11322278&dopt=Abstract acyclovir Zovirax

chem.sinica.edu.tw

A novel strategy was developed for the synthesis of N(7)-purine acyclic nucleosides 9 and 14. The key step involved the reaction between [2-(p-methoxyphenyloxy)ethoxy]methyl chloride and N(9)-tritylated nucleobases 6 or 11 followed by concomitant self-detritylation. N(7)-Guanine acyclic nucleoside 9 exhibited antiviral activity, but was phosphorylated by both HSV and Vero cell thymidine kinases. Thus, it showed more potent cellular toxicity than acyclovir (2). N(7)-Adenine acyclic nucleoside 14 was found to be an excellent antiviral agent as well as a good inhibitor of calf mucosal adenosine deaminase. This inhibitory property allows for a greater expression of antiviral activity of antiviral agents, such as N(9)-adenine acyclic nucleoside 1 and ara-A (3). Compound 14 was phosphorylated neither by herpes simplex virus (HSV) thymidine kinase nor by Vero cell thymidine kinase, yet it enhanced the rate constant for the monophosphorylation of acyclovir (2) by HSV thymidine kinase. Consequently, the combination of acyclovir (2) and 14 exhibited greater antiviral activity than acyclovir alone. 7-[2-(Phosphonomethoxy)ethyl]adenine (20) was also synthesized. The key step involved the reaction of 9-(2-cyanoethyl)adenine (15) with methyl iodoacetate in the presence of lithium 2,2,6,6-tetramethylpiperidine in THF. Unlike 9-[2-(phosphonomethoxy)ethyl]adenine (PMEA, 4), the N(7)-isomer 20 was not phosphorylated effectively by 5-phosphoribosyl 1-pyrophosphate synthetase (PRPP synthetase). Thus, it did not exhibit pronounced antiviral activity. Dinucleotide 5'-monophosphate 24 and its butenolide ester 25 were also synthesized. Compound 24 showed substrate activity toward PRPP synthetase and exhibited notable activity against DNA viruses. The antiviral activity of the ester derivative 25 was found to be higher than that of the parent molecule 24. Dinucleotide 5'-monophosphate 24 is susceptible to degradation by snake venom and spleen phosphodiesterases. However, its respective butenolide ester derivative 25 was completely resistant to snake venom and spleen enzymes. Butenolide ester derivatives 28 and 29 were also synthesized and exhibited notable anti-DNA virus and anti-retrovirus activity in vitro. Compounds 2, 4, 9, 14, 20, 24, 25, and 28 were also evaluated for their inhibitory effect on HSV-1-induced mortality in NMRI mice. N(7)-adenine acyclic nucleoside 14 [LD(50) (intraperitoneal, ip) 950 mg/kg], nucleotide-containing butenolide 25 [LD(50) (ip) 675 mg/kg], and butenolide 28 [LD(50) (ip) 710 mg/kg] were found to be potent anti-HSV-1 agents in vivo. In addition, butenolide 28 efficiently decreased tumor formation induced by Moloney murine sarcoma virus (MSV) in NMRI mice while significantly increasing the survival time of MSV-infected mice.

Online pharmacy ref source - acyclovir: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11606136&dopt=Abstract acyclovir Zovirax




Antiviral Res. 2001 Oct;52(1):19-24.
Lack of effect of treatment with penciclovir or acyclovir on the establishment of latent HSV-1 in primary sensory neurons in culture.

Smith RL, Morroni J, Wilcox CL.

Department of Neurology and Pediatrics, University of Colorado Health Sciences Center, Denver, CO, USA.

Recent studies suggest reductions in establishment of herpes simplex virus, type 1 (HSV-1) latency using the nucleoside analog penciclovir compared with acyclovir in the murine model. These observations raise the possibility that the new analogs may have novel activities that directly interfere with the establishment of the latent infection, suggesting a mechanism other than simply blocking the productive infection. To determine if penciclovir has a direct action on the establishment of latency, we compared the effects of penciclovir versus acyclovir in an in vitro model of HSV-1 latency in rat dorsal root ganglia neurons in culture. In neurons in culture, both penciclovir and acyclovir were highly effective in blocking the productive infection. However, neither penciclovir nor acyclovir blocked establishment of latency as demonstrated by similar percentages of neurons expressing the latency-associated transcript (LAT). Following removal of the respective nucleoside analog, latency was maintained until reactivation was induced by nerve growth factor deprivation. Similar virus titers were recovered after induction of reactivation of latent infections, which were established in the presence of either penciclovir or acyclovir. These results indicate that neither penciclovir nor acyclovir treatment directly prevents the establishment of latent HSV-1 infections in primary sensory neurons in culture.

Online pharmacy ref source - acyclovir: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11530184&dopt=Abstract acyclovir Zovirax




Clin Infect Dis. 1998 Dec;27(6):1525-7.
Acyclovir-resistant herpes zoster in human immunodeficiency virus-infected patients: results of foscarnet therapy.

Breton G, Fillet AM, Katlama C, Bricaire F, Caumes E.

Department of Infectious and Tropical Diseases, Hopital Pitie Salpetriere, Paris, France.

We retrospectively studied 18 consecutive cases of acyclovir-resistant zoster. All the patients had chronic skin lesions that failed to heal despite treatment with intravenous acyclovir (30 mg/[kg.d]) in 15 cases and oral acyclovir (4 g/d) in three cases for > 10 days. The mean CD4+ cell count was 20 x 10(6)/L. The mean number of previous zoster episodes was 1.53. Fifteen of the 16 patients evaluable for previous acyclovir treatment had received the drug. Thirteen patients were treated with intravenous foscarnet (200 mg/[kg.d]) for a mean of 17.8 days. Complete healing was observed in 10 (77%) of the 13 treated patients. Zoster relapsed after cessation of foscarnet therapy in five of the 10 responding patients. The median time to relapse was 110 days. Four patients died of varicella-zoster virus-associated visceral complications. These results show that acyclovir-resistant zoster has a poor prognosis but responds well to foscarnet therapy.

Online pharmacy ref source - acyclovir: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9868672&dopt=Abstract acyclovir Zovirax

hbham.ac.uk

The efficacy of early versus late treatment with acyclovir and valaciclovir on zoster-associated pain was assessed from two databases (1076 patients) that were compiled from randomized trials. Early treatment was started < 48 h and late treatment was started 48-72 h after the onset of cutaneous herpes zoster. Median times to complete resolution of zoster-associated pain were 28 and 62 days, respectively, for patients (> or = 18 years of age) treated with acyclovir and placebo within 48 h (hazard ratio [HR], 1.68; 95% confidence limit [95% CL], 1.19, 2.38) and 28 and 58 days, respectively, for those treated later (HR, 2.20; 95% CL, 1.03, 4.71). In the valaciclovir versus acyclovir study (in patients > or = 50 years of age), the corresponding figures were 44 and 51 days for patients treated early (HR, 1.28; 95% CL, 1.03, 1.60) and 36 and 48 days for those treated later (HR, 1.40; 95% CL, 1.04, 1.87). Acyclovir significantly shortened the time to complete resolution of zoster-associated pain compared with placebo (and valaciclovir was superior to acyclovir in this regard) even when therapy was delayed up to 72 h after rash onset.

Online pharmacy ref source - acyclovir: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9852981&dopt=Abstract acyclovir Zovirax