UNASSIGNED: Brivudine has been used in herpes zoster (HZ) treatment for years, but the safety and efficacy of brivudine are inconclusive. Here we perform a meta-analysis to assess the efficacy, safety, incidence of postherpetic neuralgia of brivudine.
UNASSIGNED: Data of randomized controlled Trials (RCTS) were obtained from the databases of both English (PubMed, Embase, and Cochrane Library) and Chinese (China National Knowledge Infrastructure, China Science Journal Database, and WanFang Database) literatures from inception to 12 September 2022. Meta-analyses of efficacy and safety of Brivudine for the treatment of herpes zoster for RCTS were conducted.
UNASSIGNED: The analyses included seven RCTS (2095 patients in experimental group and 2076 patients in control group) in the treatment of HZ with brivudine. It suggested that the brivudine group was superior to the control group in terms of efficacy (p = .0002) and incidence of postherpetic neuralgia (p = .04). But the incidence of adverse reactions has no significant difference between the brivudine and the control groups (p = .22). In addition, subgroup analysis of adverse events also showed that brivudine was about the same safety as other modalities in the treatment of HZ (p > .05).
UNASSIGNED: Brivudine is effective for HZ. However, the evidence on the safety of brivudine is insufficient.

暂无摘要。

UNASSIGNED: This study aimed to explore a comprehensive empirical investigation and assess SCARs related to valaciclovir or acyclovir based on FAERS database from FDA, thus providing a theoretical foundation for the rational application of drugs in clinic.
UNASSIGNED: SCARs reports relevant to valaciclovir or acyclovir were searched in FAERS database from the 2004 Q1 to 2023 Q2. These data were further mined by a proportional analysis and Bayesian approach to detect signals of SCARs caused by two drugs. Meanwhile, the clinical characteristics, onset time, correlation, and stratification analysis of the two drugs in SCARs were analyzed.
UNASSIGNED: Both drugs exhibited positive signals for drug reaction with DRESS, AGEP, TEN, SJS-TEN overlap and SJS. The median onset time of SCARs caused by valaciclovir or acyclovir was 30 days vs 10 day for DRESS, 11 days vs 9 days for AGEP, 17 days vs 12 days (TEN) and 12 days vs 8 days (SJS). Excluding the effect of combinational drugs, there was an association between the two antiviral drugs and SCARs.
UNASSIGNED: By analyzing the FAERS database, the risk trends of SCARs caused by valaciclovir or acyclovir have been identified, providing valuable insights to recognize various types of SCARs in clinics.

BACKGROUND: Valacyclovir is the only treatment demonstrated to be effective for the prevention of vertical transmission of cytomegalovirus within a clinical randomized, placebo-controlled trial and has been reimbursed by the Italian National Health System since December 2020.
OBJECTIVE: This study reported the results of a real-life Italian multicenter observational study on cytomegalovirus infection in pregnancy evaluating the effect of the introduction of valacyclovir in the clinical practice for the prevention of vertical transmission of cytomegalovirus.
METHODS: The outcomes of women who received valacyclovir treatment and their fetuses or newborns were compared with those of a retrospective cohort observed between 2010 and 2020 who did not receive the antiviral treatment. The inclusion criterion was the diagnosis of cytomegalovirus primary infection occurring in the periconceptional period or up to 24 weeks of gestation. The primary outcome was the transmission by the time of amniocentesis. The secondary outcomes were termination of pregnancy, transmission at birth, symptomatic infection at birth, and a composite outcome (termination of pregnancy or transmission at birth).
RESULTS: A total of 447 pregnant women from 10 centers were enrolled, 205 women treated with valacyclovir (called the valacyclovir group, including 1 twin pregnancy) and 242 women not treated with valacyclovir (called the no-valacyclovir group, including 2 twin pregnancies). Valacyclovir treatment was significantly associated with a reduction of the diagnosis of congenital cytomegalovirus infection by the time of amniocentesis (weighted odds ratio, 0.39; 90% confidence interval, 0.22-0.68; P=.005; relative reduction of 61%), termination of pregnancy (weighted odds ratio, 0.36; 90% confidence interval, 0.17-0.75; P=.0021; relative reduction of 64%), symptomatic congenital cytomegalovirus infection at birth (weighted odds ratio, 0.17; 90% confidence interval, 0.06-0.49; P=.006; relative reduction of 83%). The treatment had no significant effect on the rate of diagnosis of congenital cytomegalovirus infection at birth (weighted odds ratio, 0.85; 90% confidence interval, 0.57-1.26; P=.500), but the composite outcome (termination of pregnancy or diagnosis of congenital cytomegalovirus infection at birth) occurred more frequently in the no-valacyclovir group (weighted odds ratio, 0.62; 90% confidence interval, 0.44-0.88; P=.024). Of note, the only symptomatic newborns with congenital cytomegalovirus infection in the valacyclovir group (n=3) were among those with positive amniocentesis. Moreover, 19 women (9.3%) reported an adverse reaction to valacyclovir treatment, classified as mild in 17 cases and moderate in 2 cases. Lastly, 4 women (1.9%) presented renal toxicity with a slight increase in creatinine level, which was reversible after treatment suspension.
CONCLUSIONS: Our real-life data confirm that valacyclovir significantly reduces the rate of congenital cytomegalovirus diagnosis at the time of amniocentesis with a good tolerability profile and show that the treatment is associated with a reduction of termination of pregnancy and symptomatic congenital cytomegalovirus infection at birth.

Cytomegalovirus (CMV) is the most common cause of congenital infections in developed countries because is capable of infecting the fetus after both primary and recurrent maternal infection, and because the virus may be spread for years through infected children. Moreover, CMV is the most serious congenital infection associated with severe neurological and sensorineural sequelae, which can occur at birth or develop later on. Hygienic measures can prevent CMV transmission, which mainly involve contact with children under 3 years of age and attending a nursery or daycare. In animal and human pregnancies, many observational and controlled studies have shown that CMV-specific hyperimmune globulin (HIG) is safe and can significantly decrease maternal-fetal transmission of CMV infection and, mostly, the occurrence of CMV disease. Recently, valaciclovir at the dosage of 8 g/day was also reported to be capable of decreasing the rates of congenital infection and disease. However, comparing the results of our two recent case series, the infants born to women treated with HIG showed significantly lower rates of CMV DNA positivity in urine (9.7% vs. 75.0%; p < 0.0001) and abnormalities after follow-up (0.0% vs. 41.7%; p < 0.0001). The implementation of CMV screening would enable primary prevention via hygiene counseling, improve the understanding and awareness of congenital CMV infection, and increase the knowledge of the potential efficacy of preventive or therapeutic HIG or antiviral administration.

A previous randomized placebo-controlled study found valaciclovir to be effective in reducing the rate of vertical cytomegalovirus transmission from mother to fetus. The better results in women infected in the first trimester compared to the periconception period were attributed to the timing of treatment. The aim of the present study was to evaluate valaciclovir efficacy in this setting using a revised protocol.
All pregnant women treated with valaciclovir in 2020-2022 who met the same criteria as in the original study were identified retrospectively from the database of the same medical center. Treatment, however, was initiated earlier: up to 9 weeks or 8 weeks from the presumed time of infection in women infected in the periconception period or the first trimester, respectively. The primary endpoint was rate of vertical cytomegalovirus transmission. Results were compared with the placebo arm in the previous study.
Among 178 women who completed valaciclovir treatment, amniocentesis was positive for cytomegalovirus in 14 women (7.9%), significantly (P < .001) lower compared with 14 of 47 (30%) in the placebo arm in the previous study. The proportion of positive amniocentesis in the valaciclovir was significantly lower than the placebo arm both among women infected in the first trimester (14/119 vs 11/23; odds ratio [OR] = 0.15; 95% confidence interval [CI]: .05-.45, P < .001), as well as among those infected in the periconception period (0/59 vs 3/24, OR = 0; 95% CI 0-.97, P = .02).
This study provides further evidence of the efficacy of valaciclovir in preventing vertical transmission of cytomegalovirus after primary maternal infection. Efficacy is improved with earlier treatment.

Epstein-Barr virus (EBV) frequently is measured at high levels in COPD using sputum quantitative polymerase chain reaction, whereas airway immunohistochemistry analysis has shown EBV detection to be common in severe disease.
Is valaciclovir safe and effective for EBV suppression in COPD?
The Epstein-Barr Virus Suppression in COPD (EViSCO) trial was a randomized double-blind placebo-controlled trial conducted at the Mater Hospital Belfast, Northern Ireland. Eligible patients had stable moderate-to-severe COPD and sputum EBV (measured using quantitative polymerase chain reaction) and were assigned randomly (1:1) to valaciclovir (1 g tid) or matching placebo for 8 weeks. The primary efficacy outcome was sputum EBV suppression (defined as ≥ 90% sputum viral load reduction) at week 8. The primary safety outcome was the incidence of serious adverse reactions. Secondary outcome measures were FEV1 and drug tolerability. Exploratory outcomes included changes in quality of life, sputum cell counts, and cytokines.
From November 2, 2018, through March 12, 2020, 84 patients were assigned randomly (n = 43 to valaciclovir). Eighty-one patients completed trial follow-up and were included in the intention-to-treat analysis of the primary outcome. A greater number of participants in the valaciclovir group achieved EBV suppression (n = 36 [87.8%] vs n = 17 [42.5%]; P < .001). Valaciclovir was associated with a significant reduction in sputum EBV titer compared with placebo (-90,404 copies/mL [interquartile range, -298,000 to -15,200 copies/mL] vs -3,940 copies/mL [interquartile range, -114,400 to 50,150 copies/mL]; P = .002). A statistically nonsignificant 24-mL numerical FEV1 increase was shown in the valaciclovir group (difference, -44 mL [95% CI, -150 to 62 mL]; P = .41). However, a reduction in sputum white cell count was noted in the valaciclovir group compared with the placebo group (difference, 2.89 [95% CI, 1.5 × 106-7.4 × 106]; P = .003).
Valaciclovir is safe and effective for EBV suppression in COPD and may attenuate the sputum inflammatory cell infiltrate. The findings from the current study provide support for a larger trial to evaluate long-term clinical outcomes.
ClinicalTrials.gov; No.: NCT03699904; URL: www.
gov.

BACKGROUND: Zostavax, the live-attenuated vaccine used to prevent herpes zoster (HZ), has been available to individuals aged 70 and 71-79 years (phased catch-up) via Australia\'s National Immunisation Program (NIP) since 2016. There are limited data characterising the incidence of HZ at the level of the Australian population. National prescription data for antivirals used to treat HZ may be used as a proxy for HZ incidence. We aimed to examine trends in antiviral prescriptions supplied for the treatment of HZ in Australia pre- and post-2016, and to assess whether Zostavax\'s inclusion on the NIP correlated with a reduction in HZ antiviral prescription rates.
METHODS: Using the Australian Pharmaceutical Benefits Scheme and Repatriation Pharmaceutical Benefits Scheme prescribing data, we analysed antiviral prescriptions supplied for the treatment of HZ Australia-wide between 1994 and 2019. Annual prescription rates were calculated, and trends and changes in HZ antiviral use were explored descriptively and using Poisson models.
RESULTS: HZ antiviral prescription rates increased 2.6-fold (160%) between 1995 and 2015 [25.4 (95% CI 25.2, 25.6) and 65.3 (95% CI 64.9, 65.6) prescriptions per 10,000 people, respectively], and then decreased 0.45-fold (55%) between 2016 and 2018 [60.9 (95% CI 60.6, 61.2) and 27.5 (95% CI 27.3, 27.9) prescriptions per 10,000 people, respectively]. The prescription rate for the antiviral famciclovir restricted specifically for treating HZ in immunocompromised individuals increased 8.5-fold (750%) between 2006 (year first listed) and 2019 [0.3 (95% CI 0.3, 0.3) and 2.5 (95% CI 2.4, 2.6) prescriptions per 10,000 people, respectively].
CONCLUSIONS: The introduction of the live-attenuated HZ vaccine on Australia\'s formal national vaccination program was associated with a reduction in HZ antiviral prescription rates within the Australian population. The data suggest that the introduction of Shingrix, the non-live subunit zoster vaccine, may also be associated with a similar reduction in HZ antiviral prescriptions used to treat the immunocompromised, as well as the general population, given its accepted greater efficacy over Zostavax.

BACKGROUND: Cytomegalovirus (CMV) infection increases mortality and morbidity following allogeneic hematopoietic stem-cell transplantation (alloHSCT). Universal antiviral prophylaxis with letermovir is effective but unsubsidized in Australia. Valaciclovir demonstrates anti-CMV activity in high doses, but few current real-world studies explore its use as primary prophylaxis in high-risk patients post-alloHSCT.
METHODS: We performed a retrospective analysis of alloHSCT recipients at high risk of clinically significant CMV infection (cs-CMVi), defined as a plasma CMV DNA viral load of >400 IU/ml requiring preemptive therapy, or CMV disease. High-risk recipients were CMV seropositive and underwent T-cell depleted, haploidentical or umbilical cord stem-cell transplants. Consecutive patients transplanted from July 2018 to January 2020, treated with valaciclovir 2 g TDS from day +7 to +100 (HD-VALA), were compared to a historical cohort (July 2017-June 2018) who only received preemptive CMV therapy, and standard valaciclovir (SD-VALA) for varicella/herpes prophylaxis. We compared incidence of and time to cs-CMVi.
RESULTS: In the SD-VALA cohort (n = 27, median CMV follow-up duration 259 days), 23/27 (85%) developed cs-CMVi at a median of 39 days. For the HD-VALA cohort (n = 35, median CMV follow-up duration 216 days), 19/35 (54%) developed cs-CMVi, at a median of 68 days. Time to cs-CMVi was significantly longer in HD-VALA cohort (p < .0001). On multivariate analysis, HD VALA reduced the risk of cs-CMVi (HR 0.32, p = .0005).
CONCLUSIONS: In alloHSCT recipients at high risk for cs-CMVi, HD-VALA resulted in lower cumulative reactivation, and delayed reactivation, reducing requirement for preemptive CMV therapy in the early post-engraftment period.

(1) Background: What is the role of serum CMV PCR in the diagnosis of recent primary infection (PI) in pregnant women when IgG avidity is uninformative? (2) Methods: Retrospective cohort study to compare serum versus whole blood CMV PCR. (a) Qualitative assessment: CMV PCR was performed on 123 serum samples and 74 whole blood samples collected from 132 pregnant women with recent CMV PI. PCR positivity rate was used to calculate sensitivity in serum and whole blood. (b) Quantitative assessment: CMV PCR was performed on 72 paired samples of serum and whole blood collected on the same day from 57 patients. (3) Results: In pregnant women, PCR positivity rate was 89% for serum samples versus 100% in whole blood in the case of very recent PI (<15 days), but only 27% in serum versus 68% in whole blood for PI occurring from 6 weeks to 3 months before. Comparing CMV viral loads between serum and whole blood, we determined the limit of CMV DNA detection in serum as 3 log copies/mL (whole blood equivalent). (4) Conclusions: Serum CMV PCR is reliable in confirming PI in cases when only IgM is detected. It is therefore a valuable tool in introducing valaciclovir treatment as early as possible to prevent mother-to-child CMV transmission.