penciclovir and HIV-Infections

Most viral diseases, with the exception of those caused by human immunodeficiency virus, are self-limited illnesses that do not require specific antiviral therapy. The currently available antiviral drugs target 3 main groups of viruses: herpes, hepatitis, and influenza viruses. With the exception of the antisense molecule fomivirsen, all antiherpes drugs inhibit viral replication by serving as competitive substrates for viral DNA polymerase. Drugs for the treatment of influenza inhibit the ion channel M(2) protein or the enzyme neuraminidase. Combination therapy with Interferon-α and ribavirin remains the backbone treatment for chronic hepatitis C; the addition of serine protease inhibitors improves the treatment outcome of patients infected with hepatitis C virus genotype 1. Chronic hepatitis B can be treated with interferon or a combination of nucleos(t)ide analogues. Notably, almost all the nucleos(t) ide analogues for the treatment of chronic hepatitis B possess anti-human immunodeficiency virus properties, and they inhibit replication of hepatitis B virus by serving as competitive substrates for its DNA polymerase. Some antiviral drugs possess multiple potential clinical applications, such as ribavirin for the treatment of chronic hepatitis C and respiratory syncytial virus and cidofovir for the treatment of cytomegalovirus and other DNA viruses. Drug resistance is an emerging threat to the clinical utility of antiviral drugs. The major mechanisms for drug resistance are mutations in the viral DNA polymerase gene or in genes that encode for the viral kinases required for the activation of certain drugs such as acyclovir and ganciclovir. Widespread antiviral resistance has limited the clinical utility of M(2) inhibitors for the prevention and treatment of influenza infections. This article provides an overview of clinically available antiviral drugs for the primary care physician, with a special focus on pharmacology, clinical uses, and adverse effects.

Topics: Acyclovir; Adenine; Amantadine; Antiviral Agents; Comorbidity; Drug Therapy, Combination; Foscarnet; Ganciclovir; Guanine; Hepatitis; Hepatitis B, Chronic; Hepatitis C; Herpesviridae Infections; HIV Infections; Humans; Influenza, Human; Interferons; Lamivudine; Nucleosides; Oligopeptides; Organophosphonates; Oseltamivir; Proline; Protease Inhibitors; Pyrimidinones; Ribavirin; Telbivudine; Thymidine; Valacyclovir; Valganciclovir; Valine; Virus Replication; Zanamivir

The aim of this study was to present a new topical treatment protocol for oral hairy leukoplakia (OHL), consisting of a 25% podophyllin resin with a 1% penciclovir cream (PP), and to compare this topical treatment protocol's efficacy with that of 2 other topical treatment protocols: a 25% podophyllin resin (P) and a 25% podophyllin resin with a 5% acyclovir cream (PA).. Forty-two human immunodeficiency virus-positive patients with 69 OHL lesions were randomly treated using P, PA, or PP (14 patients in each topical treatment protocol). Clinical healing was determined when the white plaque could no longer be seen in the primary location of the lesion. Topical treatment performance was evaluated by clinical healing within each week of topical treatment protocol as well as by the recurrence of the lesion. Statistical survival analysis was performed using a Cox proportional hazards model.. Approximately 55% of the patients presented with clinical healing of OHL within 7-8 weeks of each topical treatment protocol. After the sixth week, the PA treatment protocol presented a faster clinical healing rate of OHL. Recurrence was observed in 3 and 7 OHL lesions treated with P and PP treatment protocols, respectively.. The PP treatment protocol proved to be effective; however, the PA treatment protocol was more effective in the clinical healing rate for OHL than P and PP after the sixth week of treatment, and no recurrent OHL was observed in the PA treatment group.

Topics: Acyclovir; Administration, Topical; Adult; Antifungal Agents; Antineoplastic Agents, Phytogenic; Antiviral Agents; Candidiasis, Oral; Double-Blind Method; Female; Follow-Up Studies; Guanine; Heterosexuality; HIV Infections; HIV Seropositivity; Humans; Leukoplakia, Hairy; Male; Middle Aged; Neoplasm Recurrence, Local; Podophyllin; Proportional Hazards Models; Remission Induction; Time Factors; Tongue Neoplasms; Treatment Outcome; Young Adult

Following our findings on the anti-human immunodeficiency virus (HIV) activity of acyclovir (ACV) phosphate prodrugs, we herein report the ProTide approach applied to a series of acyclic nucleosides aimed at the identification of novel and selective antiviral, in particular anti-HIV agents. Acyclic nucleoside analogues used in this study were identified through a virtual screening using HIV-reverse transcriptase (RT), adenylate/guanylate kinase, and human DNA polymerase γ. A total of 39 new phosphate prodrugs were synthesized and evaluated against HIV-1 (in vitro and ex vivo human tonsillar tissue system) and human herpes viruses. Several ProTide compounds showed substantial potency against HIV-1 at low micromolar range while the parent nucleosides were not effective. Also, pronounced inhibition of herpesvirus replication was observed. A carboxypeptidase-mediated hydrolysis study was performed for a selection of compounds to assess the formation of putative metabolites and support the biological activity observed.

Topics: Acyclovir; Anti-HIV Agents; Cell Line; Drug Design; Herpes Simplex; HIV Infections; HIV Reverse Transcriptase; HIV-1; Humans; Molecular Docking Simulation; Nucleosides; Simplexvirus; Virus Replication

Topics: 2-Aminopurine; Acetamides; Acyclovir; Aged; Amantadine; Animals; Anti-HIV Agents; Antiviral Agents; Child; Child, Preschool; Dose-Response Relationship, Drug; Drug Resistance, Microbial; Enzyme Inhibitors; Famciclovir; Ganciclovir; Guanidines; Guanine; Herpes Simplex; Herpes Zoster; History, 18th Century; HIV Infections; Humans; Injections, Intravenous; Interferon-alpha; Lamivudine; Neuraminidase; Oseltamivir; Pyrans; Rats; Ribavirin; Sialic Acids; Teratogens; Valacyclovir; Valine; Zanamivir