Famvir
Enhanced antiviral benefit of combination therapy with lamivudine and famciclovir against WHV replication in chronic WHV carrier woodchucks.

Korba BE, Cote P, Hornbuckle W, Schinazi R, Gerin JL, Tennant BC.

Division of Molecular Virology and Immunology, Georgetown University Medical Center, Rockville, MD, USA.

Cell culture studies in our laboratory and others have previously demonstrated synergistic antiviral activity for combinations of 3TC (lamivudine) and penciclovir against Hepatitis B Virus (HBV) replication and the Duck Hepatitis B Virus (DHBV). Based on these results, a study was designed to determine if an enhanced antiviral effect with combinations of 3TC and famciclovir (FCV, oral prodrug of penciclovir) could be demonstrated in vivo using the Woodchuck Hepatitis Virus (WHV)/woodchuck experimental model of chronic HBV infection. Both antiviral agents have been shown to be effective against WHV replication in WHV chronic carriers in previous studies by our laboratories. The antiviral effects of four different combinations of lamivudine and FCV were found to be greater than those observed for the corresponding monotherapies. All four combination treatments produced antiviral effects that were at least equal to that expected for additive activity based on estimations generated by Bliss Independence calculations. Two of the combination treatments produced antiviral effects that were significantly greater than that expected for additive effects, indicative of synergistic antiviral interactions. These studies demonstrate that combination therapy of chronic WHV infection has enhanced antiviral benefit over corresponding monotherapies and indicate that combination treatment of chronic HBV infection can be superior to therapies using a single antiviral agent.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10774587&dopt=Abstract famciclovir Famvir



Famvir
Combination treatment with famciclovir and a topical corticosteroid gel versus famciclovir alone for experimental ultraviolet radiation-induced herpes simplex labialis: a pilot study.

Spruance SL, McKeough MB.

Division of Infectious Diseases, School of Medicine, University of Utah, Salt Lake City, UT 84132, USA.

To investigate the efficacy of corticosteroids for the treatment of herpes labialis, we compared famciclovir (Famvir, 500 mg 3x/day po [per os] for 5 days) and topical fluocinonide (0.05% Lidex Gel 3x/day for 5 days) with famciclovir and topical vehicle control for experimental ultraviolet radiation-induced herpetic recurrences. We irradiated 49 volunteers, and 29 (60%) of 48 developed signs or symptoms of a recurrence. They self-initiated treatment, and we were able to evaluate them. There was a trend in the combination group toward more aborted lesions, compared with those who received antiviral therapy alone (7 [41%] of 17 vs. 1 [8%] of 12; P=.09). Combination therapy significantly reduced the median maximum lesion size (48 vs. 162 mm(2); P=.02) and the number of patients who experienced lesion pain (10 [59%] of 17 vs. 12 [100%] of 12; P=.02). Adverse events were minimal. Corticosteroids in combination with an antiviral agent may be safe and beneficial for episodic treatment of herpes labialis. Larger studies are needed to confirm these findings.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10837169&dopt=Abstract famciclovir Famvir



Famvir
Further evidence from a murine infection model that famciclovir interferes with the establishment of HSV-1 latent infections.

Thackray AM, Field HJ.

Centre for Veterinary Science, Cambridge University, Madingley Road, Cambridge CB3 0ES, UK.

Mice were infected with herpes simplex virus type 1 (HSV-1) via the ear pinna. Famciclovir therapy was commenced on days 2-7 post infection (p.i.). The ipsilateral and contralateral trigeminal (TG) and third cervical ganglia (CIII) from individual mice were tested for latency 1 and 6 months after infection by explant culture or in situ hybridization for latency-associated transcripts (LAT). There were significantly fewer LAT-positive neurons in ipsilateral and contralateral TG (but not CIII) when therapy was delayed by up to 6 days. There was a low correlation between the number of LAT-positive neurons and reactivation by explant culture. Latency data for individual ganglia, compared with those from previous studies, allow us to rationalize differences between the effects of nucleosides on the establishment of latency in different anatomical sites and when tissues are evaluated using different techniques. The implications of the findings for the use of famciclovir to counter HSV latency in humans are addressed.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10837437&dopt=Abstract famciclovir Famvir



Famvir
[Dynamic changes of hepatitis B virus during treatment with lamivudine versus lamivudine plus famciclovir]

[Article in Chinese]

Hou J, Fen X, Nie Z.

Department of Infectious Diseases, Nanfang Hospital, Guangzhou 510515, China.

OBJECTIVE: To study whether combination therapy with lamivudine (LAM) and famciclovir (FCV) is effective for treatment of Chinese chronic HBV infection. METHODS: Chronic hepatitis B-infected patients treated with either LAM (n=9, 150 mg daily for 12 weeks) or LAM plus FCV (n=12, 150 mg LAM daily plus 500 mg FCV daily for 12 weeks). Serial serum HBV DNA were determined. A mathematical model was applied to analyze the dynamics of viral clearance. RESULTS: HBV clearance from patients treated with LAM was biphasic attenuation with mean antiviral efficacy of 0.94 while a combination therapy with LAM and FCV displayed an increased mean antiviral efficacy of 0. 988. There was an increased magnitude of the first phase of clearance from 1.1 log(10) to 1.9 log(10). Mean log(10) HBV viral decline were 1.8A0.2 for LAM treated group and 2.5A0.8 for combination group. CONCLUSION: Combination therapy of LAM and FCV has higher efficacy than LAM alone in suppressing HBV replication in Chinese chronic HBeAg-positive carriers.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10861109&dopt=Abstract famciclovir Famvir



Famvir
[Therapy of recurrent hepatitis B infection after liver transplantation. A retrospective analysis of 200 liver transplantations based on hepatitis B associated liver diseases]

[Article in German]

Seehofer D, Rayes N, Bechstein WO, Naumann U, Neuhaus R, Berg T, Hopf U, Langrehr JM, Steinmuller T, Platz KP, Muller AR, Neuhaus P.

Klinik fur Allgemein-, Viszeral- und Transplantationschirurgie, Humboldt-Universitat zu Berlin. daniel.seehofer charite.de

BACKGROUND: Before introduction of passive immunoprophylaxis and new antiviral nucleoside analogues the course of hepatitis B recurrence after liver transplantation could hardly be influenced. The result was a inferior graft survival. In the present retrospective analysis of the efficacy of hepatitis B therapy after liver transplantation was analysed retrospectively. PATIENTS AND METHODS: Between 1988 and 1998 in total 179 patients were transplanted due to hepatitis B related liver failure at our centre. All patients received passive immunoprophylaxis with hepatitis B immunoglobulin. In case of reinfection after 1993 an antiviral therapy with famciclovir 1500 mg daily was initiated (n = 26), since 1996 lamivudine (100-150 mg daily) was used (n = 12). In case of viral breakthrough under famciclovir treatment or prophylaxis therapy was switched to lamivudine (n = 22). In case of ineffectiveness of lamivudine an antiviral combination therapy with lamivudine and interferon (n = 4) or lamivudine and famciclovir (n = 4) was initiated. Before availability of antiviral agents or in case of viral breakthrough in total 12 patients were retransplanted due to acute or chronic reinfection. RESULTS: With passive immunoprophylaxis reinfection rate was 33%, 43% and 44% after 1, 3 and 5 years respectively. Without antiviral treatment 52% of patients died within the first year after reinfection. Antiviral therapy with lamivudine or famciclovir improved the one year survival after reinfection to 79%. Suppression of viral replication was more effective with lamivudine. Under lamivudine 26 patients (76%) became HBV-DNA negative, 9 patients HBsAg negative (26%). In contrast no patient became HBsAg negative during famciclovir therapy. Lamivudine was effective also after famciclovir breakthrough in 94% of patients. In case of lamivudine resistant reinfection viral replication could be suppressed with an antiviral combination therapy up to negative HBV-DNA in the hybridization assay. Severe side effects were not observed during any of the antiviral therapies. The graft survival after retransplantation for hepatitis B reinfection was 42% and 25% after one and 3 years. CONCLUSION: Whereas it is generally accepted, that passive immunoprophylaxis lowers the reinfection rate it could be shown in the present study, that antiviral treatment lowers mortality of hepatitis B reinfection. The major problem of lamivudine and famciclovir is viral resistance formation. In this case an antiviral combination therapy might be useful, whereas retransplantation for hepatitis B reinfection should be considered carefully due to inferior graft survival rates.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11072673&dopt=Abstract famciclovir Famvir