今日の臨床サポート 今日の臨床サポート

著者: 森博威 順天堂大学医学部総合診療科学講座/マヒドン大学熱帯医学部

監修: 上原由紀 藤田医科大学医学部感染症科

著者校正/監修レビュー済:2024/06/12
患者向け説明資料

改訂のポイント:
  1. 定期レビューを行った(大きな変更なし)。

概要・推奨   

  1. 初感染のヘルペス歯肉口内炎・咽頭炎に対しては、アシクロビルを5~10日間投与することにより、解熱までの期間、口腔内病変が消退するまでの期間、嚥下痛のみられる期間、ウイルスの排出期間を短くすることができる(推奨度2)
  1. 口唇ヘルペスの再燃では、アシクロビル400 mgを1日5回5日間内服することでウイルス排出、疼痛期間、治癒までの期間を短縮することができる(推奨度2)
  1. アシクロビルの局所製剤は口唇ヘルペスの再燃の病期をわずかに短縮することが可能である(推奨度3)
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病態・疫学・診察 

疾患情報(疫学・病態)  
  1. 世界で50歳未満の37億人(67%)が単純ヘルペスウイルス1型(HSV-1)に感染していると推定される[1]
  1. HSV-1は皮膚や粘膜を介して感染する。口や外陰部を介して伝播することが多い。
  1. HSV-1は無症候性感染が多い。有症状では初感染時には歯肉口内炎・咽頭炎を呈することが多く、再発例では口唇ヘルペスの頻度が高い。いずれも感染部位に疼痛を伴う水疱や潰瘍を起こす。
  1. HSV-1の感染の多くは親密な接触で感染する。家族内感染やパートナーを介した感染、および小児期のデイケアセンターでの感染が報告されている[2]
  1. HSV-2は性行為で感染し、性器や肛門に症状を(性器ヘルペス)を引き起こす。
  1. HSV-1感染症でも、口と性器との接触を通して性器に感染し、性器ヘルペスを引き起こすことがある。近年、わが国ではHSV-1による性器ヘルペスの増加が指摘されている(参照: 性器ヘルペス )。
  1. 臨床検査による確定診断は、非典型的な臨床症状である場合、中枢神経系の症状を呈する場合(参照: HSV脳炎 )、免疫不全がある場合などで必要となる。
  1. HSV-1感染症の臨床診断にはウイルス培養、PCR、血清学的検査などがあるが、わが国で保険適用内で実施できる臨床検査としては特異抗原検査がある。
  1. 水疱内容液を用いたウイルス培養はわが国では保険適用外で検査結果が得られるまでに時間がかかるため、臨床の場で実施される機会は限定的である。
病歴・診察のポイント  
  1. 最近口唇ヘルペスを発症している家族や友人との接点はなかったか、ヘルペス感染症のリスクの高い職業ではないか、これまでにヘルペスの既往はないか、ヘルペスの再活性化が起こる危険因子(ストレス、日光曝露、発熱、顔面領域の手術など)はないかを確認する。

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最新のエビデンスに基づいた二次文献データベース「今日の臨床サポート」。
常時アップデートされており、最新のエビデンスを各分野のエキスパートが豊富な図表や処方・検査例を交えて分かりやすく解説。日常臨床で遭遇するほぼ全ての症状・疾患から薬剤・検査情報まで瞬時に検索可能です。

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文献 

World Health Organization:Herpes simplex virus.
K Kuzushima, H Kimura, Y Kino, S Kido, N Hanada, M Shibata, T Morishima
Clinical manifestations of primary herpes simplex virus type 1 infection in a closed community.
Pediatrics. 1991 Feb;87(2):152-8.
Abstract/Text The clinical features and the molecular epidemiology of primary herpes simplex virus type 1 (HSV-1) infection among children younger than 3 years of age were investigated in day-care nursery. Serial sera were assayed for anti-HSV-1 glycoprotein B antibody by enzyme-linked immunosorbent assay. Serologic examinations revealed 55 cases of primary HSV infection during the observation period. Fifty-one of them (93%) had typical herpetic gingivostomatitis, showing a high rate of clinically overt infection. Four outbreaks of herpetic gingivostomatitis were observed during the observation period. Forty-one children were infected with HSV-1 in the outbreaks. The rates of infection in the susceptible children were 81%, 73%, 78%, and 100%, respectively, in the four outbreaks. Restriction endonuclease analysis of DNA of isolated HSV revealed that only one strain of HSV-1 had been transmitted among children for a long period.

PMID 1846235
J F Rooney, Y Bryson, M L Mannix, M Dillon, C R Wohlenberg, S Banks, C J Wallington, A L Notkins, S E Straus
Prevention of ultraviolet-light-induced herpes labialis by sunscreen.
Lancet. 1991 Dec 7;338(8780):1419-22.
Abstract/Text Sunlight exposure is reported by some patients to precede onset of recurrent herpes labialis. Ultraviolet (UV) B light is known to be a stimulus for the reactivation of herpes simplex virus (HSV) infections. We assessed the effect of a sunblocking agent on UV-light-induced reactivation of recurrent herpes labialis in a double-blind, placebo-controlled crossover trial. 38 patients were exposed on two separate occasions to four minimum erythema doses of UV light at an area of previous labial herpes recurrence. A solution containing sunscreen was applied to the lips before one exposure and a matched placebo before the other. After placebo and UV exposure, herpes labialis developed in 27 (71%) of the 38 patients, with a mean time to recurrence of 2.9 (SEM 0.2) days. In contrast, when sunscreen was applied before UV exposure, no lesions developed, but 1 of the 35 patients shed virus at the exposure site. We conclude that UV light is a potent stimulus for inducing reactivation of herpes labialis, and that application of sunscreen may be effective in the prevention of sunlight-induced recurrent infection.

PMID 1683420
G W Raborn, A Y Martel, M G Grace, W T McGaw
Oral acyclovir in prevention of herpes labialis. A randomized, double-blind, multi-centered clinical trial.
Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1998 Jan;85(1):55-9.
Abstract/Text OBJECTIVE: A three-center, randomized, double-blind, placebo-controlled acyclovir clinical trial was conducted among Canadian skiers over a 2-year period.
STUDY DESIGN: All patients enrolled in the study reported a history of recurrent herpes labialis with a greater-than-50% chance of a sun-induced trigger. There were 239 patients enrolled, and 237 of these were included in the analysis. For a minimum of 3 days and a maximum of 7 days, each patient received 800 mg of oral acyclovir twice daily (1600 mg/day) 12 to 24 hours before exposure to the sun. A minimum of 3 hours of outdoor activity was required each day.
RESULTS: No differences were detected in baseline and outcome measures among the centers, and results from all three centers were combined for further analysis. There was no difference in healing rate between the acyclovir and placebo groups for the first 4 days. Patients using acyclovir healed slightly faster on days 5 and 6, and nearly all patients in both the acyclovir and placebo groups were healed by day 7. Adverse events were evenly distributed; no withdrawals were required in either group.
CONCLUSION: 800-mg oral acyclovir taken twice a day was not significantly better than a placebo either in effectiveness and prevention of recurrent herpes labialis or in adverse effects.

PMID 9474615
S L Spruance, M L Hamill, W S Hoge, L G Davis, J Mills
Acyclovir prevents reactivation of herpes simplex labialis in skiers.
JAMA. 1988 Sep 16;260(11):1597-9.
Abstract/Text To determine the effectiveness of an antiviral to prevent herpes labialis during a brief, high-risk circumstance, 147 persons with a history of sun-induced recurrences were treated prophylactically with oral acyclovir or matching placebo and were observed during their ski holidays. Five (7%) of 75 acyclovir-treated subjects developed lesions compared with 19 (26%) of 72 persons in the placebo group.

PMID 3411740
J A McMillan, L B Weiner, A M Higgins, V J Lamparella
Pharyngitis associated with herpes simplex virus in college students.
Pediatr Infect Dis J. 1993 Apr;12(4):280-4.
Abstract/Text During a 16-month period patients who presented to the Syracuse University Health Center with upper respiratory complaints had throat swabs obtained for viral, streptococcal and Mycoplasma pneumoniae cultures. Thirty-five of 613 patients (5.7%) had herpes simplex virus (HSV) isolated. All but 2 of the HSV isolates were found to be type 1 by immunofluorescent staining. Two HSV-positive patients also grew Group A Streptococcus, one grew M. pneumoniae and three had serum heterophile antibody tests that were positive. On physical examination 25 of the 35 HSV-positive patients had pharyngeal erythema and 14 had pharyngeal exudate. Twelve of these patients had vesicular lesions of the lips, throat or gums associated with their other symptoms. For 29 of the 35 HSV-positive students the primary diagnosis assigned was pharyngitis, for 2 the diagnosis was stomatitis and the remainder were assigned a primary diagnosis of upper respiratory infection, pneumonia, bronchitis or dental infection. Thirty-two of the 35 HSV-positive patients were treated with oral antibiotics and 7 were treated with oral or topical acyclovir. During the same 16-month period 89 (6.9%) of 1297 students presenting with sore throat were culture-positive for influenza A or B, 30 (2.3%) of 1283 were culture-positive for M. pneumoniae and 169 (2.8%) of the 6016 cultured for Group A Streptococcus were positive. Serum was tested for heterophile antibody in 2438 students, and 257 (10.5%) were positive. Herpes simplex virus is associated with pharyngeal symptoms in college students, and herpes simplex pharyngitis cannot easily be distinguished clinically from other causes of acute pharyngitis in this age group.

PMID 8387178
J Amir, L Harel, Z Smetana, I Varsano
Treatment of herpes simplex gingivostomatitis with aciclovir in children: a randomised double blind placebo controlled study.
BMJ. 1997 Jun 21;314(7097):1800-3.
Abstract/Text OBJECTIVES: To examine the efficacy of aciclovir suspension for treating herpetic gingivostomatitis in young children.
DESIGN: Randomised double blind placebo controlled study.
SETTING: Day care unit of a tertiary paediatric hospital.
SUBJECTS: 72 children aged 1-6 years with clinical manifestations of gingivostomatitis lasting less than 72 hours; 61 children with cultures positive for herpes simplex virus finished the study.
MAIN OUTCOME MEASURES: Duration of oral lesions, fever, eating and drinking difficulties, and viral shedding.
INTERVENTION: Aciclovir suspension 15 mg/kg five times a day for seven days, or placebo.
RESULTS: Children receiving aciclovir had oral lesions for a shorter period than children receiving placebo (median 4 v 10 days (difference 6 days, 95% confidence interval 4.0 to 8.0)) and earlier disappearance of the following signs and symptoms: fever (1 v 3 days (2 days, 0.8 to 3.2)); extraoral lesions (lesions around the mouth but outside the oral cavity) (0 v 5.5 days (5.5 days, 1.3 to 4.7)); eating difficulties (4 v 7 days (3 days, 1.31 to 4.69)); and drinking difficulties (3 v 6 days (3 days, 1.1 to 4.9)). Viral shedding was significantly shorter in the group treated with aciclovir (1 v 5 days (4 days, 2.9 to 5.1)).
CONCLUSIONS: Oral aciclovir treatment for herpetic gingivostomatitis, started within the first three days of onset, shortens the duration of all clinical manifestations and the infectivity of affected children. Further studies are needed to evaluate the ideal dose and length of treatment.

PMID 9224082
S Gilbert, E McBurney
Use of valacyclovir for herpes simplex virus-1 (HSV-1) prophylaxis after facial resurfacing: A randomized clinical trial of dosing regimens.
Dermatol Surg. 2000 Jan;26(1):50-4.
Abstract/Text BACKGROUND: Reactivation of herpes simplex virus-1 (HSV-1) after facial resurfacing has led to severe outbreaks, delayed reepitheliazation, and scarring. Current recommendations regarding the dosing of antivirals used prophylactically are based mostly on anecdotal experience. No studies have addressed the question of when such antiviral prophylaxis should begin.
OBJECTIVE: The purpose of this study was to compare the efficacy of valacyclovir used as an antiviral prophylaxis when started the morning before versus the morning of facial resurfacing procedures.
METHODS: Eighty-four patients who presented for facial resurfacing were enrolled. Resurfacing was performed using laser (CO2, Er:YAG), chemical peeling, dermabrasion/dermasanding, or some combination of these techniques. Patients were randomly assigned to start valacyclovir 500 mg twice daily either the morning before or the morning of the procedure. Viral cultures were performed at baseline on all patients, at any sign of infection, and at the end of the 14-day treatment period. All patients were followed for 21 days postoperatively.
RESULTS: Valacyclovir was 100% effective in the prevention of HSV reactivation in both regimens with no adverse effects reported.
CONCLUSION: This study demonstrates the efficacy of valacyclovir as a preventive agent against HSV outbreaks following facial resurfacing whether started the day before or the day of surgery.

PMID 10632686
J Schädelin, H U Schilt, M Rohner
Preventive therapy of herpes labialis associated with trigeminal surgery.
Am J Med. 1988 Aug 29;85(2A):46-8.
Abstract/Text Acyclovir was shown to limit herpes simplex reactivation in a controlled trial to prevent herpes labialis after surgical intervention for trigeminal neuralgia. Of 14 patients receiving acyclovir, unambiguous herpes labialis developed in only one, compared with 12 of 16 in the placebo group.

PMID 3044092
S Safrin, C Crumpacker, P Chatis, R Davis, R Hafner, J Rush, H A Kessler, B Landry, J Mills
A controlled trial comparing foscarnet with vidarabine for acyclovir-resistant mucocutaneous herpes simplex in the acquired immunodeficiency syndrome. The AIDS Clinical Trials Group.
N Engl J Med. 1991 Aug 22;325(8):551-5. doi: 10.1056/NEJM199108223250805.
Abstract/Text BACKGROUND AND METHODS: Most strains of herpes simplex virus that are resistant to acyclovir are susceptible in vitro to both foscarnet and vidarabine. We conducted a randomized trial to compare foscarnet with vidarabine in 14 patients with the acquired immunodeficiency syndrome (AIDS) and mucocutaneous herpetic lesions that had been unresponsive to intravenous therapy with acyclovir for a minimum of 10 days. The patients were randomly assigned to receive either foscarnet (40 mg per kilogram of body weight intravenously every 8 hours) or vidarabine (15 mg per kilogram per day intravenously) for 10 to 42 days. In the isolates of herpes simplex virus we documented in vitro resistance to acyclovir and susceptibility to foscarnet and vidarabine.
RESULTS: The lesions in all eight patients assigned to foscarnet healed completely after 10 to 24 days of therapy. In contrast, vidarabine was discontinued because of failure in all six patients assigned to receive it. The time to complete healing (P = 0.01), time to 50 percent reductions in the size of the lesions (P = 0.01) and the pain score (P = 0.004), and time to the end of viral shedding (P = 0.006) were all significantly shorter in the patients assigned to foscarnet. Three patients had new neurologic abnormalities while receiving vidarabine. No patient discontinued foscarnet because of toxicity. Although initial recurrences of herpes simplex infection after the index lesion had healed tended to be susceptible to acyclovir, acyclovir-resistant infection eventually recurred in every healed patient, a median of 42.5 days (range, 14 to 191) after foscarnet was discontinued.
CONCLUSIONS: For the treatment of acyclovir-resistant herpes simplex infection in patients with AIDS, foscarnet has superior efficacy and less frequent serious toxicity than vidarabine. Once the treatment is stopped, however; there is a high frequency of relapse.

PMID 1649971
Emilie Frobert, Sonia Burrel, Sophie Ducastelle-Lepretre, Geneviève Billaud, Florence Ader, Jean-Sébastien Casalegno, Viviane Nave, David Boutolleau, Mauricette Michallet, Bruno Lina, Florence Morfin
Resistance of herpes simplex viruses to acyclovir: an update from a ten-year survey in France.
Antiviral Res. 2014 Nov;111:36-41. doi: 10.1016/j.antiviral.2014.08.013. Epub 2014 Sep 8.
Abstract/Text The widespread use of acyclovir (ACV) and the increasing number of immunocompromised patients have raised concern about an increase in ACV-resistant herpes simplex virus (HSV). ACV resistance has traditionally been a major concern for immunocompromised patients with a frequency reported between 2.5% and 10%. The aim of this study was to reassess the status of HSV resistance to ACV in immunocompetent and immunocompromised patients over a ten year period, between 2002 and 2011. This was done by retrospectively following 1425 patients. In immunocompetent patients, prevalence of resistance did not exceed 0.5% during the study period; whereas in immunocompromised patients, a significant increase was observed, rising from 3.8% between 2002 and 2006 (7/182 patients) to 15.7% between 2007 and 2011 (28/178) (p=0.0001). This sharp rise in resistance may largely be represented by allogeneic hematopoietic stem cell transplant patients, in which the prevalence of ACV resistance rose similarly from 14.3% (4/28) between 2002 and 2006 to 46.5% (26/56) between 2007 and 2011 (p=0.005). No increase in ACV resistance was detected in association with other types of immune deficiencies. Genotypic characterization of HSV UL23 thymidine kinase and UL30 DNA polymerase genes revealed 11 and 7 previously unreported substitutions, respectively. These substitutions may be related to potential polymorphisms, drug resistance, or other mutations of unclear significance.

Copyright © 2014 Elsevier B.V. All rights reserved.
PMID 25218782
S L Spruance, J C Stewart, N H Rowe, M B McKeough, G Wenerstrom, D J Freeman
Treatment of recurrent herpes simplex labialis with oral acyclovir.
J Infect Dis. 1990 Feb;161(2):185-90.
Abstract/Text In a double-blind, randomized, patient-initiated clinical trial, 174 nonimmunocompromised patients with a history of virus-culture-confirmed herpes simplex labialis were treated with acyclovir capsules, 400 mg five times daily for 5 days, or placebo capsules. For 97% of the patients, treatment started within 1 h of the first sign or symptom of a recurrence. The frequency of positive lesion virus cultures was significantly lower among acyclovir-treated subjects (29/114, 25%) than among placebo-treated subjects (29/60, 48%; P = .004). Drug treatment did not affect the development of lesions, measured by the frequency of macular and papular (aborted) lesions and mean maximum lesion size. However, acyclovir hastened lesion resolution among the patients who could start treatment in the prodrome or erythema lesion stage. For this group, the mean duration of pain was reduced by 36% (P = .02) and the mean healing time to loss of crust by 27% (P = .03). Thus, oral acyclovir alleviated some of the clinical manifestations of herpes simplex labialis.

PMID 2153735
J F Rooney, S E Straus, M L Mannix, C R Wohlenberg, D W Alling, J A Dumois, A L Notkins
Oral acyclovir to suppress frequently recurrent herpes labialis. A double-blind, placebo-controlled trial.
Ann Intern Med. 1993 Feb 15;118(4):268-72.
Abstract/Text OBJECTIVE: To determine whether oral acyclovir reduces the incidence of recurrent herpes labialis in otherwise healthy patients with proven frequently recurrent disease.
DESIGN: Randomized, double-blind, placebo-controlled, crossover trial.
SETTING: Outpatient facility of the Clinical Center, National Institutes of Health, Bethesda, Maryland.
PATIENTS: Fifty-six otherwise healthy adults who reported frequently recurrent herpes labialis (> or = 6 episodes/y) were enrolled into the study. During a 4-month observation period, 22 patients had herpes labialis two or more times and were eligible for study treatment.
INTERVENTIONS: Twenty-two patients were randomized to receive either acyclovir, 400 mg twice daily, or matched placebo for 4 months. After the first treatment period, patients were given the alternate treatment for another 4 months and were then taken off study medication to observe the first post-treatment recurrence. Recurrent outbreaks were determined by examination and by viral culture.
RESULTS: Twenty patients completed blind treatment with both acyclovir and placebo. The median time to first clinically documented recurrence was 46 days for placebo courses and 118 days for acyclovir courses (P = 0.05). The mean number of recurrences per 4-month treatment period was 1.80 episodes per patient during placebo treatment and 0.85 episodes per patient during acyclovir treatment (P = 0.009). The mean number of virologically confirmed recurrences per patient was 1.40 with placebo therapy compared with 0.40 with acyclovir (P = 0.003).
CONCLUSIONS: Oral acyclovir, 400 mg twice daily, is effective in suppressing herpes labialis in immunocompetent adults confirmed to have frequently recurrent infection. Treatment with acyclovir in this study resulted in a 53% reduction in the number of clinical recurrences and a 71% reduction in virus culture-positive recurrences compared with placebo therapy.

PMID 8380540
David Baker, Drore Eisen
Valacyclovir for prevention of recurrent herpes labialis: 2 double-blind, placebo-controlled studies.
Cutis. 2003 Mar;71(3):239-42.
Abstract/Text The oral antiviral valacyclovir, which is 3 to 5 times more bioavailable than its parent compound acyclovir, is a good candidate for effective therapy to suppress recurrent herpes labialis lesions. The efficacy of oral valacyclovir in the suppression of herpes labialis has not previously been reported. Two identical, randomized, double-blind, parallel-group studies were conducted to evaluate the efficacy of oral valacyclovir 500 mg (n=49) versus placebo (n=49) once daily for 16 weeks in the suppression of herpes labialis among patients with a history of 4 or more recurrent lesions in the previous year. Data from the studies were pooled for analysis. Twenty-eight patients (60%) in the valacyclovir group compared with only 18 patients (38%) in the placebo group were recurrence-free throughout the 4-month treatment period (P=.041). The mean time to first recurrence was significantly longer with valacyclovir (13.1 weeks) compared with placebo (9.6 weeks) (P=.016). The total number of recurrences in patients using valacyclovir was 24 compared with 41 in patients using placebo. The incidence of adverse events during the 4-month treatment period was slightly lower in the valacyclovir group (22 events, 33% of patients) compared with the placebo group (29 events, 39% of patients). The results of these small double-blind, placebo-controlled studies suggest that oral valacyclovir 500 mg once daily for 4 months is effective and well tolerated for the prevention of recurrent herpes labialis. More research with larger patient numbers is warranted to corroborate and extend these findings.

PMID 12661753
Spotswood L Spruance, Terry M Jones, Mark M Blatter, Mauricio Vargas-Cortes, Judy Barber, Joanne Hill, Donna Goldstein, Margaret Schultz
High-dose, short-duration, early valacyclovir therapy for episodic treatment of cold sores: results of two randomized, placebo-controlled, multicenter studies.
Antimicrob Agents Chemother. 2003 Mar;47(3):1072-80.
Abstract/Text Oral valacyclovir is better absorbed than oral acyclovir, increasing acyclovir bioavailability three- to fivefold. This provides the opportunity to explore whether high systemic acyclovir concentrations are effective in the treatment of cold sores (herpes labialis). Two randomized, double-blind, placebo-controlled studies were conducted. Subjects were provided with 2 g of valacyclovir twice daily for 1 day (1-day treatment), 2 g of valacyclovir twice daily for 1 day and then 1 g of valacyclovir twice daily for 1 day (2-day treatment), or a matching placebo and instructed to initiate treatment upon the first symptoms of a cold sore. In study 1, the median duration of the episode (primary endpoint) was reduced by 1.0 day (P = 0.001) with 1-day treatment and 0.5 days (P = 0.009) with 2-day treatment compared to placebo. Similarly, the mean duration of the episode was statistically significantly reduced by 1.1 days with 1-day treatment and 0.7 days with 2-day treatment compared to placebo. The proportion of subjects in whom cold sore lesion development was prevented and/or blocked was increased by 6.4% (P = 0.096) with 1-day treatment and 8.5% (P = 0.061) with 2-day treatment compared to placebo. The time to lesion healing and time to cessation of pain and/or discomfort were statistically significantly reduced with valacyclovir compared to placebo. In study 2, results similar to those in study 1 were obtained. AEs were similar across treatment groups. These studies provide evidence supporting a simple, 1-day valacyclovir treatment regimen for cold sores that is safe and effective. The 1-day valacyclovir regimen offers patients a unique and convenient dosing alternative compared to available topical therapies.

PMID 12604544
Spotswood L Spruance, Robert Nett, Thomas Marbury, Ray Wolff, James Johnson, Theodore Spaulding
Acyclovir cream for treatment of herpes simplex labialis: results of two randomized, double-blind, vehicle-controlled, multicenter clinical trials.
Antimicrob Agents Chemother. 2002 Jul;46(7):2238-43.
Abstract/Text Acyclovir cream has been available for the treatment of herpes labialis in numerous countries outside the United States for over a decade. Evidence for its efficacy comes from a few small clinical trials conducted in the 1980s. To examine more comprehensively the efficacy and safety of this formulation, we conducted two independent, identical, parallel, randomized, double-blind, vehicle-controlled, large-scale multicenter clinical trials. Healthy adults with a history of frequent herpes labialis were recruited from the general population, screened for eligibility, randomized equally to 5% acyclovir cream or vehicle control, given study medication, and told to self-initiate treatment five times daily for 4 days beginning within 1 h of the onset of a recurrent episode. The number of patients who treated a lesion was 686 in study 1 and 699 in study 2. In study 1, the mean duration of episodes was 4.3 days for patients treated with acyclovir cream and 4.8 days for those treated with the vehicle control (hazards ratio [HR] = 1.23; 95% confidence interval [CI], 1.06 to 1.44; P = 0.007). In study 2, the mean duration of episodes was 4.6 days for patients treated with acyclovir cream and 5.2 days for those treated with the vehicle control (HR = 1.24; 95% CI, 1.06 to 1.44; P = 0.006). Efficacy was apparent whether therapy was initiated "early" (prodrome or erythema lesion stage) or "late" (papule or vesicle stage). There was a statistically significant reduction in the duration of lesion pain in both studies. Acyclovir cream did not prevent the development of classical lesions (progression to vesicles, ulcers, and/or crusts). Adverse events were mild and infrequent.

PMID 12069980
日本造血細胞移植学会:造血細胞移植ガイドライン ウイルス感染症の予防と治療 ヘルペスウイルス感染(HSV/VZV)、2018年2月.
Marcie Tomblyn, Tom Chiller, Hermann Einsele, Ronald Gress, Kent Sepkowitz, Jan Storek, John R Wingard, Jo-Anne H Young, Michael J Boeckh, Michael A Boeckh, Center for International Blood and Marrow Research, National Marrow Donor program, European Blood and MarrowTransplant Group, American Society of Blood and Marrow Transplantation, Canadian Blood and Marrow Transplant Group, Infectious Diseases Society of America, Society for Healthcare Epidemiology of America, Association of Medical Microbiology and Infectious Disease Canada, Centers for Disease Control and Prevention
Guidelines for preventing infectious complications among hematopoietic cell transplantation recipients: a global perspective.
Biol Blood Marrow Transplant. 2009 Oct;15(10):1143-238. doi: 10.1016/j.bbmt.2009.06.019.
Abstract/Text
PMID 19747629
K Kawamura, H Wada, R Yamasaki, Y Ishihara, K Sakamoto, M Ashizawa, M Sato, T Machishima, K Terasako, S I Kimura, M Kikuchi, H Nakasone, R Yamazaki, J Kanda, S Kako, A Tanihara, J Nishida, Y Kanda
Low-dose acyclovir prophylaxis for the prevention of herpes simplex virus disease after allogeneic hematopoietic stem cell transplantation.
Transpl Infect Dis. 2013 Oct;15(5):457-65. doi: 10.1111/tid.12118. Epub 2013 Jul 29.
Abstract/Text BACKGROUND: Currently, acyclovir (ACV) at 1000 mg/day is widely used as prophylaxis in the early phase of hematopoietic stem cell transplant (HSCT) in Japan. However, low-dose ACV (200 mg/day) has been shown to prevent varicella zoster virus reactivation in the middle and late phases of HSCT.
METHODS: Therefore, in this study, we decreased the dose of ACV to 200 mg/day in the early phase after HSCT. We analyzed 93 consecutive herpes simplex virus (HSV)-seropositive patients who underwent allogeneic HSCT for the first time in our center between June 2007 and December 2011.
RESULTS: Before August 2009, 38 patients received oral ACV at 1000 mg/day (ACV1000) until day 35 after HSCT, whereas 55 patients received oral ACV at 200 mg/day (ACV200) after September 2009. We compared the cumulative incidence of HSV infection in the 2 groups. Oral ACV was changed to intravenous administration because of intolerance in 66% and 45% of the patients in the ACV1000 and ACV200 groups, respectively (P = 0.060). The probability of severe stomatitis (Bearman grade II-III) was 76% and 60% in the ACV1000 and ACV200 groups, respectively (P = 0.12). The number of patients who developed HSV disease before day 100 after HSCT was 0 in the ACV1000 group and 2 in the ACV200 group, with a cumulative incidence of 3.6% (P = 0.43). HSV disease in the latter 2 patients was limited to the lips and tongue and was successfully treated with ACV or valacyclovir at a treatment dose.
CONCLUSION: ACV at 200 mg/day appeared to be effective for preventing HSV disease in the early phase after HSCT.

© 2013 John Wiley & Sons A/S.
PMID 23895431
薬剤監修について:
オーダー内の薬剤用量は日本医科大学付属病院 薬剤部 部長 伊勢雄也 以下、渡邉裕次、井ノ口岳洋、梅田将光および日本医科大学多摩永山病院 副薬剤部長 林太祐による疑義照会のプロセスを実施、疑義照会の対象については著者の方による再確認を実施しております。
※薬剤中分類、用法、同効薬、診療報酬は、エルゼビアが独自に作成した薬剤情報であり、 著者により作成された情報ではありません。
尚、用法は添付文書より、同効薬は、薬剤師監修のもとで作成しております。
※同効薬・小児・妊娠および授乳中の注意事項等は、海外の情報も掲載しており、日本の医療事情に適応しない場合があります。
※薬剤情報の(適外/適内/⽤量内/⽤量外/㊜)等の表記は、エルゼビアジャパン編集部によって記載日時にレセプトチェックソフトなどで確認し作成しております。ただし、これらの記載は、実際の保険適応の査定において保険適応及び保険適応外と判断されることを保証するものではありません。また、検査薬、輸液、血液製剤、全身麻酔薬、抗癌剤等の薬剤は保険適応の記載の一部を割愛させていただいています。
(詳細はこちらを参照)
著者のCOI(Conflicts of Interest)開示:
森博威 : 特に申告事項無し[2024年]
監修:上原由紀 : 研究費・助成金など(花王(株))[2024年]

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