Background: Acyclovir (ACV), a synthetic purine nucleoside analogue derived from guanosine, is known to be toxic to gonads and the aim of this study was to evaluate the effect of ACV on the sperm parameters and testosterone production in rat.Materials and Methods: In this experimental study, forty adult male Wistar rats (220±20 g) were randomly divided into five groups (n=8 for each group). One group served as control and one group served as sham control [distilled water was intraperitoneally (i.p.) injected]. ACV was administered intraperitoneally in the drug treatment groups (4, 16 and 48 mg/kg/day) for 15 days. Eighteen days after the last injection, rats were sacrificed by CO2 inhalation. After that, cauda epididymides were removed surgically. At the end, sperm concentrations in the cauda epididymis, sperm motility, morphology, viability, chromatin quality and DNA integrity were analyzed. Serum testosterone concentrations were determined. Results: The results showed that ACV did not affect sperm count, but decreased sperm motility and sperm viability at 16 and 48 mg/kg dose-levels. Sperm abnormalities increased at 48 mg/kg dose-level of ACV. Further, ACV significantly increases DNA damage at 16 and 48 mg/kg dose-levels and chromatin abnormality at all doses. Besides, a significant decrease in serum testosterone concentrations was observed at 16 and 48 mg/ kg doses.Conclusion: The present results highly support the idea that ACV induces testicular toxicity by adverse effects on the sperm parameters and serum level of testosterone in male rats.

Background: Tenofovir disoproxil fumarate (TDF) is a new effective treatment option for patients with chronic hepatitis B (CHB).Objectives: To evaluate TDF efficacy in nucleos (t)ide analogues (NAs)-naive Iranian patients with CHB.Patients and Methods: The NA-naive patients received TDF for at least six months. The primary endpoint was the proportion of patients achieving a complete virological response (CVR) during the treatment. Multivariate Cox regression analysis determined predictive factors independently associated with the time to CVR. The secondary endpoints were biochemical and serological responses, frequency of virological breakthrough, genotypic resistance development, safety and tolerability.Results: In all, 93 patients (64.5% hepatitis B e antigen [HBeAg]-negative) were eligible. Of these, 70 patients completed 24 months of treatment. The cumulative CVR rates in HBeAg-negative and HBeAg-positive patients were 87% versus 53% at 24 months, respectively. The multivariate Cox regression model showed only HBeAg positivity at baseline and a high baseline HBV DNA level were independent factors predicting a CVR. No patient achieved hepatitis B surface antigen (HBsAg) and HBeAg loss or seroconversion and no virologic breakthrough occurred. A new amino acid substitution (rtD263E) was observed to develop in 60% of patients with viremia.Conclusions: The cumulative CVR rates showed that patients with HBeAg-negative have better virologic respond than those with HBeAg-positive during the same period. The rtD263E mutation might be associated with partial resistance to TDF.

Entecavir (ETV) is a potent nucleoside analogue against hepatitis B virus (HBV). Because of development of ETV resistance requires at least three amino acid substitutions in HBV polymerase (pol) gene, emergence of ETV resistance is rare (~1%) in nucleoside-naive patients after up to 5 years of treatment. However, it has been suggested that lamivudine (LAM) therapy can preselect for HBV variants associated with resistance to ETV treatment. ETV resistance increased to 51% of patients after 5 years of ETV treatment in LAM refractory patients. The diagnosis of ETV resistance in chronic hepatitis B patients, mainly based on four types of molecular assays: direct sequencing, line probe assay, clonal analysis, and restriction fragment length polymorphism (RFLP) analysis. The applications of other assays are currently more specialized, and their use is more limited. The utility of these assays and their performance characteristics are reviewed below. Briefly, the monitoring of drug-resistant variants is important in the elucidation of the prevalence and mechanisms of resistance development and for the more effective management of treatment options.