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Background. Orally administered antiviral therapy for genital herpes improves the time to lesion healing and resolves symptoms during an outbreak. Although traditional therapy for a recurrent episode for healthy adults has consisted of twice-daily dosing for 5 days, recent studies have indicated that shorter courses of antiviral therapy are effective. This study was conducted to assess the efficacy and safety of a patient-initiated, single-day regimen of famciclovir therapy, compared with placebo, in immunocompetent adult patients with recurrent genital herpes. Methods. This multicenter, multinational, randomized, double-blind, parallel-group, placebo-controlled study compared single-day, patient-initiated oral famciclovir (1000 mg given twice daily) with placebo for the treatment of recurrent genital herpes. Patients were instructed to initiate therapy within 6 h after onset of prodromal symptoms or genital herpes lesions. Results. Famciclovir reduced (P <.001) the time to healing of nonaborted lesions (i.e., those that did not progress beyond the papule stage) (median time, 4.3 vs. 6.1 days) and all nonaborted and aborted lesions (median time, 3.5 vs. 5.0 days), compared with placebo. The proportion of patients with aborted lesions was larger in the famciclovir group than in the placebo group (23.3% vs. 12.7%; P =.003). Adverse events in the famciclovir group were infrequent overall; most were of mild-to-moderate severity and were similar to adverse events in the placebo group. Conclusions. A single-day regimen of patient-initiated famciclovir treatment was well tolerated and safe, and the healing of recurrent genital herpes lesions occurred ∼2 days faster than with placebo. Moreover, single-day famciclovir treatment stopped the development or progression of lesions beyond the papule stage. This convenient single-day regimen has the potential for improving patient compliance and satisfaction with therapy.

Two general measures are available to reduce the impact of influenza: immunization with inactivated vaccines and antiviral prophylaxis and therapy with amantadine and rimantadine. 1 The usefulness of amantadine and rimantadine is limited by an antiviral spectrum restricted to influenza A viruses, their uncertain effectiveness in severe influenza or in preventing complications, side effects, and the emergence of drug-resistant variants. 2 Consequently, there is a continuing need for more effective antiviral agents to manage influenza infections. The sialic acid analogue zanamivir (GG167) is a potent, specific inhibitor of influenzavirus neuraminidase. 3 , 4 This enzyme, essential for replication in vitro, 5 cleaves terminal sialic acid . . .

Background: Daily antiviral therapy with famciclovir and valacyclovir has been shown to be effective in reducing both symptomatic and asymptomatic reactivation of herpes simplex virus type 2 (HSV-2) when compared to placebo. However, few comparative studies between the 2 antivirals have been performed. Objectives: To compare the clinical and virologie effects of famciclovir and valacyclovir administered as daily suppressive therapy for persons with genital herpes. Study Design: Two randomized, double-blind, placebo-controlled studies comparing daily famciclovir 250 mg bid with valacyclovir 500 mg qd were performed. Study 1 randomized 320 participants and compared the clinical effect of the drugs given for 16 weeks, and study 2 enrolled 70 HSV-2 seropositive subjects and compared the virologie effect of the drugs given for 10 weeks. Results: In study 1, the time to first recurrence was similar in famciclovir and valacyclovir recipients, hazard ratio (HR) 1.17 (95% CI, 0.78-1.76), but time to first virologically confirmed recurrence was shorter among famciclovir recipients, HR = 2.15 (95% CI, 1.00-4.60). In study 2, HSV was detected on 3.2% of days among famciclovir recipients and 1.3% of days among valacyclovir recipients, relative risk 2.33 (95% CI, 1.18-4.89). Conclusion: Valacyclovir appear to be somewhat better than famciclovir for suppression of genital herpes and associated shedding. Further comparative trials of antiviral drugs for various indications should be performed as acyclovir and penciclovir appear to have different ability to abrogate HSV reactivation.

Background. Two previous trials have suggested that a herpes simplex virus (HSV) type 2 glycoprotein D (gD) vaccine combined with the adjuvants alum and 3′-O-deacylated-monophosphoryl lipid A (MPL) is well tolerated and provides protection against genital herpes disease in women with no preexisting HSV antibody. Methods. The safety and immunogenicity of this vaccine were evaluated in a large, multicenter, double-blind, randomized, placebo-controlled trial. The effects of sex and preexisting HSV immunity were sought. Results. When solicited symptoms that continued after the initial 4 days of observation were excluded, the incidence of unsolicited symptoms occurring during the 7 months after vaccination (the primary analysis period) was 22.1% in vaccine recipients and 21.9% in placebo recipients. Significant increases in the number of local and systemic symptoms were found in vaccine recipients within 4 days after vaccination. However, most symptoms were mild to moderate in severity and were short lived. Women reported symptoms more frequently than did men, but preexisting immunity had little effect. The vaccine induced higher titers of HSV gD antibody on enzyme-linked immunosorbent assays than did natural infection with HSV. Conclusion. The vaccine was generally safe, well tolerated, and immunogenic.

This article represents the second update to the AMMI Canada Guidelines document on the use of antiviral drugs for influenza. The article aims to inform health care professionals of the increased risk for influenza in long-term care facilities due to a documented mismatch between the components chosen for this season's vaccine and currently circulating influenza strains. Adjusted recommendations for the use of antiviral drugs for influenza in the acute care setting for this season are provided.

The control arm of PATRICIA (PApilloma TRIal against Cancer In young Adults, NCT00122681) was used to investigate the risk of progression from cervical HPV infection to cervical intraepithelial neoplasia (CIN) or clearance of infection, and associated determinants. Women aged 15-25 years were enrolled. A 6-month persistent HPV infection (6MPI) was defined as detection of the same HPV type at two consecutive evaluations over 6 months and clearance as ≥2 type-specific HPV negative samples taken at two consecutive intervals of approximately 6 months following a positive sample. The primary endpoint was CIN grade 2 or greater (CIN2+) associated with the same HPV type as a 6MPI. Secondary endpoints were CIN1+/CIN3+ associated with the same HPV type as a 6MPI; CIN1+/CIN2+/CIN3+ associated with an infection of any duration; and clearance of infection. The analyses included 4825 women with 16,785 infections (3363 women with 6902 6MPIs). Risk of developing a CIN1+/CIN2+/CIN3+ associated with same HPV type as a 6MPI varied with HPV type and was significantly higher for oncogenic versus non-oncogenic types. Hazard ratios for development of CIN2+ were 10.44 (95% CI: 6.96-15.65), 9.65 (5.97-15.60), 5.68 (3.50-9.21), 5.38 (2.87-10.06) and 3.87 (2.38-6.30) for HPV-16, HPV-33, HPV-31, HPV-45 and HPV-18, respectively. HPV-16 or HPV-33 6MPIs had ~25-fold higher risk for progression to CIN3+. Previous or concomitant HPV infection or CIN1+ associated with a different HPV type increased risk. Of the different oncogenic HPV types, HPV-16 and HPV-31 infections were least likely to clear. Cervical infections with oncogenic HPV types increased the risk of CIN2+ and CIN3+. Previous or concomitant infection or CIN1+ also increased the risk. HPV-16 and HPV-33 have by far the highest risk of progression to CIN3+, and HPV-16 and HPV-31 have the lowest chance of clearance.

Two double-blind, controlled trials assessed the efficacy of a glycoprotein-D–subunit vaccine to prevent genital herpes disease. The vaccine elicited humoral and cellular responses, but efficacy was found only in women who were seronegative for both herpes simplex virus type 1 (HSV-1) and herpes simplex virus type 2 (HSV-2) (efficacy in the two studies was 73 and 74 percent). The vaccine was not efficacious in women who were seronegative for HSV-2 if they were seropositive for HSV-1, nor was it efficacious in men. Genital infection caused by herpes simplex virus type 1 (HSV-1) or herpes simplex virus type 2 (HSV-2) may be asymptomatic, mild, and unrecognized as herpes or severe with painful skin lesions and complications including urinary retention and meningitis, as well as substantial psychological illness. 1 – 8 Genital HSV infection occurs worldwide and appears to be epidemic in some populations despite the availability of condoms and chemoprophylaxis. 9 – 11 Evidence suggests that only the widespread use of an effective vaccine might control this epidemic. 12 We describe the results of two multicenter, double-blind, randomized, controlled studies of an HSV-2 glycoprotein-D–subunit vaccine formulated with a . . .

The AMMI Canada Guidelines document 'The use of antiviral drugs for influenza: A foundation document for practitioners', published in the Autumn 2013 issue of the Journal, outlines the recommendations for the use of antiviral drugs to treat influenza. This article, which represents the first of two updates to these guidelines published in the current issue of the Journal, aims to inform health care professionals of the increased risk for influenza in long-term care facilities due to a documented mismatch between the components chosen for this season's vaccine and currently circulating influenza strains. Adjusted recommendations for the use of antiviral drugs for influenza in long-term care facilities for this season are provided.

Background. We examined risk of newly detected human papillomavirus (HPV) infection and cervical abnormalities in relation to HPV type 16/18 antibody levels at enrollment in PATRICIA (Papilloma Trial Against Cancer in Young Adults; NCT00122681). Methods. Using Poisson regression, we compared risk of newly detected infection and cervical abnormalities associated with HPV-16/18 between seronegative vs seropositive women (15-25 years) in the control arm (DNA negative at baseline for the corresponding HPV type [HPV-16: n = 8193; HPV-18: n = 8463]). Results. High titers of naturally acquired HPV-16 antibodies and/or linear trend for increasing antibody levels were significantly associated with lower risk of incident and persistent infection, atypical squamous cells of undetermined significance or greater (ASCUS+), and cervical intraepithelial neoplasia grades 1/2 or greater (CIN1+, CIN2+). For HPV-18, although seropositivity was associated with lower risk of ASCUS+ and CIN1+, no association between naturally acquired antibodies and infection was demonstrated. Naturally acquired HPV-16 antibody levels of 371 (95% confidence interval [CI], 242-794), 204 (95% CI, 129-480), and 480 (95% CI, 250-5756) EU/mL were associated with 90% reduction of incident infection, 6-month persistent infection, and ASCUS+, respectively. Conclusions. Naturally acquired antibodies to HPV-16, and to a lesser extent HPV-18, are associated with some reduced risk of subsequent infection and cervical abnormalities associated with the same HPV type.