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PubMed2001

Comparative study of the efficacy and safety of valaciclovir versus acyclovir in the treatment of herpes zoster.

Acyclovir, a specific and selective inhibitor of the replication of Herpesviridae family, has well-documented efficacy and tolerability in the treatment of herpes zoster. Its limited oral bioavailability and short half-life, however, necessitates frequent dosing. Valaciclovir, the l-valyl ester of acyclovir, could be rapidly converted to acyclovir after oral administration, resulting in a three- to five-fold increase in acyclovir bioavailability compared with oral acyclovir in humans. Valaciclovir allows less frequent dosing and maintains the safety profiles of the parent drug. During the period from October 1996 through May 1998, a randomized, prospective study was performed in the Kaohsiung Veterans General Hospital to compare the safety and efficacy of valaciclovir with acyclovir in the treatment of herpes zoster in Taiwanese patients. Patients presenting with herpes zoster within 72 h after the onset of rash were enrolled and randomized to receive one of the following treatments: 1000 mg valaciclovir three times daily for 7 days or acyclovir 800 mg five times daily for 7 days. Patients were followed up for 29 days beginning with the start of therapy. A total of 57 patients were enrolled and randomized to receive valaciclovir (n = 32) or acyclovir (n = 25). Five patients in the valaciclovir group and three in the acyclovir group did not complete the study. The intent-to-treat analysis (57 patients) showed that valaciclovir significantly accelerated the resolution of herpes zoster-associated pain compared with acyclovir; on day 29, the valaciclovir group was 23% superior to the acyclovir group. There was no clinically significant difference in the nature, frequency or severity of adverse events between these two groups, although one and three adverse events were reported in the acyclovir and valaciclovir group, respectively. Thus, we conclude that in the management of herpes zoster, valaciclovir accelerates the resolution of pain and offers a simpler dosing, and maintains the favorable safety profile of acyclovir.

Acyclovir↗
PubMed2001

Recent developments in herpesvirus therapy.

The antiherpes drugs, aciclovir and ganciclovir, are considered the standard treatments and prophylactic agents for infections caused by herpes simplex virus (HSV), varicella zoster virus (VZV) and cytomegalovirus (CMV). Until a decade ago, the impact of aciclovir on the control of severe and life-threatening herpesvirus infections was unprecedented. During the past few years, we have witnessed approval of new therapeutic drugs for infections caused by HSV and VZV (i.e. penciclovir and the oral prodrugs, valaciclovir and famciclovir), CMV (i.e. ganciclovir, cidofovir and fomivirsen) or HSV, VZV and CMV (i.e. foscarnet). A few agents, such as brivudin and benzimidavir, are in ongoing clinical development; others have been suspended because of safety concerns. New antiherpes agents are needed to face clinical issues such as drug resistance, increased use of antiherpes prophylaxis in transplantation and safety concerns in small children or pregnant women.

2-Aminopurine↗
PubMed1998

[Study on liver targeted valaciclovir polybutylcyanoacrylate nanoparticles].

The valaciclovir polybutylcyanoacrylate nanoparticles (VACA-PBCA-NP) were prepared by emulsion polymerization method. The morphology, size and size distribution, release characteristics in vitro, drug loading, stability and distribution of VACV-PBCA-NP in mice were studied. The results showed that the dav = 104.77 +/- 11.78 nm, drug loading was 11.20%. The release characteristics in vitro was in accord with two-phase kinetics. 74.49% of the VACV were concentrated in liver at 15 min after i.v. VACA-PBCA-NP. The amount of VACV entering hepatocytes was also increased greatly. This research seems to have important value for increasing the anti-hepatitis B virus effect and decreasing toxicity of VACV.

Acyclovir↗
PubMed2002

[Genital herpes: epidemiology, transmission, clinic, asymptomatic viral excretion, impact on other sexually transmitted diseases, prevention, and treatment].

Genital herpes is one of the most widespread sexually transmitted diseases in the world. HSV2 predominates (60-80 p. 100), but the prevalence of HSV1 genital herpes is rising (20-40 p. 100). Erosive lesions of the genital organs due to HSV infection are a factor favoring HIV contamination and other sexually transmitted diseases. The main factor of transmission is asymptomatic viral excretion. Aciclovir, valaciclovir and famciclovir are effective treatment for genital herpes (primary infection, curative and preventive treatment of recurrence), but none of these compounds alters the natural history of the infection. Aciclovir given as a preventive measure reduces the load of asymptomatic viral excretion. Information and education of patients with genital herpes are key elements for prevention. Use of preservatives appears to be effective. New vaccine strategies favoring humoral and cellular response should be studied.

2-Aminopurine↗
PubMed2002

[National survey of dermatologists].

OBJECTIVE: The purpose of this survey was to ascertain current management practices of French dermatologists treating immunocompetent patients with cutaneomucosal herpes (ocular herpes excluded) as a prelude to the French consensus conference on this topic. METHOD: A random sample of French dermatologists were invited to respond to a telephone interview: 928 dermatologists were contacted. RESULTS: The 216 dermatologists who responded to the telephone interview provided care for five persons per month (pregnancy excluded) who consulted for orofacial or genital herpes. Nearly half of the dermatologists stated they do not talk about herpes spontaneously with their patients. When a suspect lesion is seen for the first time, 48 p. 100 of the dermatologists order one or two complementary exams. Their advice on prevention between partners basically concerns use of preservatives. Therapeutic attitudes vary depending on the type of herpes or the number of recurrences per year: 84 p. 100 of the dermatologists prescribe a specific antiviral treatment for patients with solar herpes. Virological proof of infection is not acquired in 84 p. 100 of the cases before initiating a long-term treatment for recurrence. The most widely used agents are valaciclovir 500 and aciclovir 200. CONCLUSION: This survey demonstrates a certain degree of divergence from the recommendations of the consensus conference. The participation rate appears to be satisfactory, but herpes serology is ordered too often and antiviral agents are not used in compliance with current guidelines. This survey will be redone after diffusion of the guidelines in order to evaluate their impact.

Acyclovir↗
PubMed2002

[National survey of gynecologists-obstetricians and general practitioners].

OBJECTIVE: The purpose of this survey was to ascertain current practices of French gynecologists-obstetricians (GO) and general practitioners (GP) treating immunocompetent patients with cutaneomucosal herpes (ocular lesions excluded) as a prelude to the French consensus conference on this topic. METHODS: A random sample of French GOs and GPs were invited to respond to a telephone interview: 330 GOs and 331 GPs were contacted. RESULTS: Response rate was 24 p. 100 among the GOs who could be contacted (49 responses) and 14 p. 100 among the GPs (45 responses). More than half the GPs cared for 1 to 5 cases of orofacial or genital herpes monthly. When a suspect lesion is seen for the first time, 51 p. 100 of the GOs order one or two tests to achieve virology proof: 65 p. 100 order herpes serology and 47 p. 100 PCR. For the GPs, 56 p. 100 do not order a complementary exam. Advice on prevention between partners basically concerns use of preservatives. The therapeutic attitude varies depending on the type of herpes and the number of recurrences per year. The most widely used agent is valaciclovir. A specific antiviral agent is prescribed for non-ocular herpes by 92 p. 100 of the GOs and 98 p. 100 of the GPs. Virological proof of herpes infection is not obtained by 65 p. 100 of the GOs and 78 p. 100 of the GPs before initiating long-term treatment for recurrence. Genital herpes during pregnancy appears to be rare; 57 p. 100 of the GOs had less than one case over the last five years. Only 33 p. 100 of them discuss herpes spontaneously with their consultants. When a suspect genital lesion is observed during pregnancy, 82 p. 100 seek virological proof. When there is a risk of neonatal herpes, the type of delivery depends on the type of herpes infection and the date of occurrence during the pregnancy. Cesarean section is performed systematically by 63 p. 100 of the GOs when there is a primary herpes infection after 34 weeks gestation. Most practitioners did not respond concerning their attitude for exams and surveillance for the infant. DISCUSSION: The number of responding practitioners was too small in this study to provide a representative sample. This study will be renewed with a larger sample of GOs in order to obtain reliable data. For general practitioners, there is a need for education concerning management of cutaneomucosal herpes which should be provided at the same time as the consensus conference guidelines are distributed.

Acyclovir↗
PubMed2002

[Antiviral and non-antiviral general treatments for oro-facial and genital herpes (pregnancy and neonates excluded)].

General treatments for immunocompetent individuals with herpes simplex infections are based on the use of antiviral agents which constitute the only treatment with proven efficacy. Antivirals were developed in the 1980s with aciclovir (ACV) as the leading compound and have greatly changed management. However, once the virus has penetrated the organism, it cannot be eradicated, neither by the immune system nor by antiviral agents. This viral resistance is basically related to its capacity to maintain itself in a latent form in the sensorial ganglions. ACV is the first line treatment, used since the 1980s; other antiviral agents are also available.

Acyclovir↗
PubMed2002

[Valaciclovir].

Valaciclovir is an aciclovir pro-drug considerably improving its oral availability. Its antiviral activity in vivo is related to that of aciclovir, the principle target of which is the herpes virus. Following digestive absorption, valaciclovir is rapidly transformed into aciclovir. The mean absolute bioavailability of aciclovir is of 54.2% after a single oral dose of 1,000 mg of valaciclovir, i.e., a bioavailability 3 to 5-fold greater than after oral ingestion of aciclovir. The plasma pharmacokinetic profile of valaciclovir and aciclovir observed in volunteers infected by HIV is superimposable on that of healthy subjects. In elderly patients, exposure to aciclovir is enhanced, probably because of the alteration in glomerular filtration. In patients exhibiting agranulocytosis following poly-chemotherapy, the pharmacokinetic parameters are superimposable on those observed in healthy patients. In patients with hepatic failure, there appears no need to adapt the dose, since exposure to aciclovir does not appear altered. However, the dose of valaciclovir must be adapted to renal function. During the first-episode of herpes genitalis, valaciclovir, at the dose of 500 or 1,000 mg twice daily, is as effective as 200 mg of aciclovir five times per day. In recurrent herpes genitalis, 500 mg twice daily of valaciclovir is as effective as 1,000 mg twice daily or 200 mg five times a day of aciclovir. Valaciclovir prevents recurrence herpes genitalis with a dose-dependent effect, and doses of 500 and 1,000 mg/day are as effective as 400 mg twice daily of aciclovir. There are few studies on the efficacy of valaciclovir in the treatment of oro-facial herpes. In the treatment of herpes zoster in patients aged over 50, the principle benefit provided by valaciclovir at the dose of 1,000 mg twice daily, is the decrease in the percentage of patients presenting post-zoster pain and its duration. High doses of valaciclovir (8 capsules/day) provide efficient prevention of infections related to the cyto-megalo-virus (CMV) in immunodepressed patients due to HIV infection or following renal transplantation. Tolerance to valaciclovir, like its active metabolite aciclovir, is generally good. Central neurological toxicity is frequently observed with high doses, but regresses on withdrawal. The official indications in France are the curative and preventive treatment of herpes genitalis infections, the prevention of post-zoster pain and the ocular complications of ophthalmologic herpes in immunocompetent adults, and the prevention of CMV infections after organ grafting.

Acyclovir↗
PubMed2002

Recurrent herpes simplex virus type 2 meningitis: a case report of Mollaret's meningitis.

It is well known that herpes simplex virus (HSV) type 2 produces acute meningitis, while HSV type 2 rarely causes recurrent meningitis (Mollaret's meningitis). We report the history of a 40-year-old patient with recurrent HSV type 2 meningitis (Mollaret's meningitis). The patient had seven episodes of meningeal symptoms within a 7-year period. In the seventh episode, HSV type 2 DNA was confirmed by nested polymerase chain reaction (PCR) with the cerebrospinal fluid (CSF). A real-time quantitative PCR study of the first CSF sample detected 2,000 copies of the HSV genome, which rapidly disappeared following treatment with acyclovir. The present case may be the first case of HSV type 2 Mollaret's meningitis to be documented in Japan. In our case, HSV serum antibody titers were at low levels during the whole course of the disease. The possible pathophysiology of this case is discussed.

Acyclovir↗