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Developmental Medicine and Child... Aug 2017To conduct a systematic literature review on patients with biphasic disease with herpes simplex virus (HSV) encephalitis followed by anti-N-methyl-D-aspartate receptor... (Review)
Review
AIM
To conduct a systematic literature review on patients with biphasic disease with herpes simplex virus (HSV) encephalitis followed by anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis.
METHOD
We conducted a case report and systematic literature review (up to 10 December 2016), focused on differences between herpes simplex encephalitis (HSE) and anti-NMDAR encephalitis phases, age-related characteristics of HSV-induced anti-NMDAR encephalitis, and therapy. For statistical analyses, McNemar's test, Fisher's test, and Wilcoxon rank sum test were used (two-tailed significance level set at 5%).
RESULTS
Forty-three patients with biphasic disease were identified (31 children). Latency between HSE and anti-NMDAR encephalitis was significantly shorter in children than adults (median 24 vs 40.5d; p=0.006). Compared with HSE, anti-NMDAR encephalitis was characterized by significantly higher frequency of movement disorder (2.5% vs 75% respectively; p<0.001), and significantly lower rate of seizures (70% vs 30% respectively; p=0.001). Compared with adults, during anti-NMDAR encephalitis children had significantly more movement disorders (86.7% children vs 40% adults; p=0.006), fewer psychiatric symptoms (41.9% children vs 90.0% adults; p=0.025), and a slightly higher median modified Rankin Scale score (5 in children vs 4 in adults; p=0.015). During anti-NMDAR encephalitis, 84.6 per cent of patients received aciclovir (for ≤7d in 22.7%; long-term antivirals in 18.0% only), and 92.7 per cent immune therapy, but none had recurrence of HSE clinically or using cerebrospinal fluid HSV polymerase chain reaction (median follow-up 7mo).
INTERPRETATION
Our review suggests that movement disorder may help differentiate clinically an episode of HSV-induced anti-NMDAR encephalitis from HSE relapse. Compared with adults, children have shorter latency between HSE and anti-NMDAR encephalitis and, during anti-NMDAR encephalitis, more movement disorder, fewer psychiatric symptoms, and slightly more severe disease. According to our results, immune therapy given for HSV-induced anti-NMDAR encephalitis does not predispose patients to HSE recurrence.
Topics: Adult; Anti-N-Methyl-D-Aspartate Receptor Encephalitis; Child; Encephalitis, Herpes Simplex; Female; Humans; Mental Disorders; Movement Disorders; Simplexvirus
PubMed: 28439890
DOI: 10.1111/dmcn.13448 -
The Cochrane Database of Systematic... Dec 2016Infectious mononucleosis (IM) is a clinical syndrome, usually caused by the Epstein Barr virus (EPV), characterised by lymphadenopathy, fever and sore throat. Most cases... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Infectious mononucleosis (IM) is a clinical syndrome, usually caused by the Epstein Barr virus (EPV), characterised by lymphadenopathy, fever and sore throat. Most cases of symptomatic IM occur in older teenagers or young adults. Usually IM is a benign self-limiting illness and requires only symptomatic treatment. However, occasionally the disease course can be complicated or prolonged and lead to decreased productivity in terms of school or work. Antiviral medications have been used to treat IM, but the use of antivirals for IM is controversial. They may be effective by preventing viral replication which helps to keep the virus inactive. However, there are no guidelines for antivirals in IM.
OBJECTIVES
To assess the effects of antiviral therapy for infectious mononucleosis (IM).
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 3, March 2016), which contains the Cochrane Acute Respiratory Infections (ARI) Group's Specialised Register, MEDLINE (1946 to 15 April 2016), Embase (1974 to 15 April 2016), CINAHL (1981 to 15 April 2016), LILACS (1982 to 15 April 2016) and Web of Science (1955 to 15 April 2016). We searched the World Health Organization (WHO) International Clinical Trials Registry Platform and ClinicalTrials.gov for completed and ongoing trials.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) comparing antivirals versus placebo or no treatment in IM. We included trials of immunocompetent participants of any age or sex with clinical and laboratory-confirmed diagnosis of IM, who had symptoms for up to 14 days. Our primary outcomes were time to clinical recovery and adverse events and side effects of medication. Secondary outcomes included duration of abnormal clinical examination, complications, viral shedding, health-related quality of life, days missing from school or work and economic outcomes.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed studies for inclusion, assessed the included studies' risk of bias and extracted data using a customised data extraction sheet. We used the GRADE criteria to rate the quality of the evidence. We pooled heterogeneous data where possible, and presented the results narratively where we could not statistically combine data.
MAIN RESULTS
We included seven RCTs with a total of 333 participants in our review. Three trials studied hospitalised patients, two trials were conducted in an outpatient setting, while the trial setting was unclear in two studies. Participants' ages ranged from two years to young adults. The type of antiviral, administration route, and treatment duration varied between the trials. The antivirals in the included studies were acyclovir, valomaciclovir and valacyclovir. Follow-up varied from 20 days to six months. The diagnosis of IM was based on clinical symptoms and laboratory parameters.The risk of bias for all included studies was either unclear or high risk of bias. The quality of evidence was graded as very low for all outcomes and so the results should be interpreted with caution. There were statistically significant improvements in the treatment group for two of the 12 outcomes. These improvements may be of limited clinical significance.There was a mean reduction in 'time to clinical recovery as assessed by physician' of five days in the treatment group but with wide confidence intervals (CIs) (95% CI -8.04 to -1.08; two studies, 87 participants). Prospective studies indicate that clinical signs and symptoms may take one month or more to resolve and that fatigue may be persistent in approximately 10% of patients at six-month follow-up, so this may not be a clinically meaningful result.Trial results for the outcome 'adverse events and side effects of medication' were reported narratively in only five studies. In some reports authors were unsure whether an adverse event was related to medication or complication of disease. These results could not be pooled due to the potential for double counting results but overall, the majority of trials reporting this outcome did not find any significant difference between treatment and control groups.There was a mean reduction in 'duration of lymphadenopathy' of nine days (95% CI -11.75 to -6.14, two studies, 61 participants) in favour of the treatment group.In terms of viral shedding, the overall effect from six studies was that viral shedding was suppressed while on antiviral treatment, but this effect was not sustained when treatment stopped.For all other outcomes there was no statistically significant difference between antiviral treatment and control groups.
AUTHORS' CONCLUSIONS
The effectiveness of antiviral agents (acyclovir, valomaciclovir and valacyclovir) in acute IM is uncertain. The quality of the evidence is very low. The majority of included studies were at unclear or high risk of bias and so questions remain about the effectiveness of this intervention. Although two of the 12 outcomes have results that favour treatment over control, the quality of the evidence of these results is very low and may not be clinically meaningful. Alongside the lack of evidence of effectiveness, decision makers need to consider the potential adverse events and possible associated costs, and antiviral resistance. Further research in this area is warranted.
Topics: Acute Disease; Acyclovir; Adolescent; Adult; Antiviral Agents; Child; Child, Preschool; Female; Guanine; Humans; Infectious Mononucleosis; Male; Randomized Controlled Trials as Topic; Valacyclovir; Valine; Young Adult
PubMed: 27933614
DOI: 10.1002/14651858.CD011487.pub2 -
The Cochrane Database of Systematic... Nov 2016Ocular herpes is a viral infection of the eye caused by the herpes simplex virus (HSV), a double-stranded DNA virus. Corneal scarring caused by herpes simplex keratitis... (Review)
Review
BACKGROUND
Ocular herpes is a viral infection of the eye caused by the herpes simplex virus (HSV), a double-stranded DNA virus. Corneal scarring caused by herpes simplex keratitis (HSK) is the leading infectious cause of penetrating corneal graft in high-income countries. Acyclovir is an antiviral drug known to have a protective effect against recurrences in herpetic eye disease. While there are some studies which have evaluated the effects of intervention with oral antiviral in preventing such recurrences in people with corneal grafts, a systematic review of all comparative clinical trials has not been previously undertaken.
OBJECTIVES
To assess the efficacy of oral antivirals such as acyclovir in any dosage when taken for six months or more, in preventing recurrence of herpetic keratitis in people having corneal graft surgery for herpetic keratitis.
SEARCH METHODS
We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register) (2016, Issue 5), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to June 2016), Embase (January 1980 to June 2016), the ISRCTN registry (www.isrctn.com/editAdvancedSearch), ClinicalTrials.gov (www.clinicaltrials.gov), and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 1 June 2016. We handsearched conference proceedings and contacted authors of the included studies and researchers active in the field.
SELECTION CRITERIA
We included randomised controlled trials (RCTs). People enrolled in these trials had corneal grafts for HSK. The intervention was oral antivirals for six months or more following the corneal graft surgery, and this was compared to no treatment or placebo.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed trial quality and extracted data. We contacted trial investigators for any clarification or missing information. We graded the certainty of the evidence using GRADE.
MAIN RESULTS
We included three trials, involving 126 participants, comparing the use of oral acyclovir to no treatment or placebo. Two studies were conducted in single centres in Turkey and the USA, and one was multi-centred in the Netherlands. In general, the studies were poorly reported and it was difficult to judge the extent to which bias had been avoided.Oral acyclovir may reduce the risk of recurrence of herpetic keratitis (risk ratio (RR) 0.29, 95% confidence interval (CI) 0.13 to 0.64, 126 people, low-certainty evidence). Based on data from the included trials, this corresponds to approximately 23 fewer cases of HSK recurrence (95% CI 29 fewer cases to 12 fewer cases) per 100 corneal graft operations if oral acyclovir is used.Oral acyclovir may reduce the risk of graft failure (RR 0.40, 95% CI 0.16 to 0.97, 126 people, low-certainty evidence). Based on data from the included trials, this corresponds to approximately 13 fewer cases of graft failure (95% CI 18 fewer cases to 1 fewer cases) per 100 corneal graft operations if oral acyclovir is used.None of the studies reported any serious side effects of the antivirals necessitating stoppage or change. None of the trials reported outcomes over the long term (more than two years) or any data on quality of life.
AUTHORS' CONCLUSIONS
Compared to placebo or to no treatment, oral antiviral (acyclovir) may reduce the risk of recurrence of herpetic keratitis in the first 12 months in eyes that have undergone corneal graft surgery.
Topics: Acyclovir; Administration, Oral; Antiviral Agents; Corneal Transplantation; Humans; Keratitis, Herpetic; Randomized Controlled Trials as Topic; Recurrence; Secondary Prevention; Time Factors
PubMed: 27902849
DOI: 10.1002/14651858.CD007824.pub2 -
The Cochrane Database of Systematic... Nov 2016Herpes zoster ophthalmicus affects the eye and vision, and is caused by the reactivation of the varicella zoster virus in the distribution of the first division of the... (Review)
Review
BACKGROUND
Herpes zoster ophthalmicus affects the eye and vision, and is caused by the reactivation of the varicella zoster virus in the distribution of the first division of the trigeminal nerve. An aggressive management of acute herpes zoster ophthalmicus with systemic antiviral medication is generally recommended as the standard first-line treatment for herpes zoster ophthalmicus infections. Both acyclovir and its prodrug valacyclovir are medications that are approved for the systemic treatment of herpes zoster. Although it is known that valacyclovir has an improved bioavailability and steadier plasma concentration, it is currently unclear as to whether this leads to better treatment results and less ocular complications.
OBJECTIVES
To assess the effects of valacyclovir versus acyclovir for the systemic antiviral treatment of herpes zoster ophthalmicus in immunocompetent patients.
SEARCH METHODS
We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register; 2016, Issue 5), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to June 2016), Embase (January 1980 to June 2016), Web of Science Conference Proceedings Citation Index-Science (CPCI-S; January 1990 to June 2016), BIOSIS Previews (January 1969 to June 2016), the ISRCTN registry (www.isrctn.com/editAdvancedSearch), ClinicalTrials.gov (www.clinicaltrials.gov), and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP; www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 13 June 2016.
SELECTION CRITERIA
We considered all randomised controlled trials (RCTs) in which systemic valacyclovir was compared to systemic acyclovir medication for treatment of herpes zoster ophthalmicus. There were no language restrictions.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected trials, evaluated the risk of bias in included trials, and extracted and analysed data. We did not conduct a meta-analysis, as only one study was included. We assessed the certainty of the evidence for the selected outcomes using the GRADE approach.
MAIN RESULTS
One study fulfilled the inclusion criteria. In this multicentre, randomised double-masked study carried out in France, 110 immunocompetent people with herpes zoster ophthalmicus, diagnosed within 72 hours of skin eruption, were treated, with 56 participants allocated to the valacyclovir group and 54 to the acyclovir group. The study was poorly reported and we judged it to be unclear risk of bias for most domains.Persistent ocular lesions after 6 months were observed in 2/56 people in the valacyclovir group compared with 1/54 people in the acyclovir group (risk ratio (RR) 1.93 (95% CI 0.18 to 20.65); very low certainty evidence. Dendritic ulcer appeared in 3/56 patients treated with valacyclovir, while 1/54 suffered in the acyclovir group (RR 2.89; 95% confidence interval (CI) 0.31 to 26.96); very low certainty evidence), uveitis in 7/56 people in the valacyclovir group compared with 9/54 in the acyclovir group (RR 0.96; 95% CI 0.36 to 2.57); very low certainty evidence). Similarly, there was uncertainty as to the comparative effects of these two treatments on post-herpetic pain, and side effects (vomiting, eyelid or facial edema, disseminated zoster). Due to concerns about imprecision (small number of events and large confidence intervals) and study limitations, the certainty of evidence using the GRADE approach was rated as low to very low for the use of valacyclovir compared to acyclovir.
AUTHORS' CONCLUSIONS
This review included data from only one study, which had methodological limitations. As such, our results indicated uncertainty of the relative benefits and harms of valacyclovir over acyclovir in herpes zoster ophthalmicus, despite its widespread use for this condition. Further well-designed and adequately powered trials are needed. These trials should include outcomes important to patients, including compliance.
Topics: Acyclovir; Antiviral Agents; Herpes Zoster Ophthalmicus; Humans; Immunocompetence; Randomized Controlled Trials as Topic; Valacyclovir; Valine
PubMed: 27841441
DOI: 10.1002/14651858.CD011503.pub2 -
The Cochrane Database of Systematic... Aug 2016Genital herpes is incurable, and is caused by the herpes simplex virus (HSV). First-episode genital herpes is the first clinical presentation of herpes that a person... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Genital herpes is incurable, and is caused by the herpes simplex virus (HSV). First-episode genital herpes is the first clinical presentation of herpes that a person experiences. Current treatment is based around viral suppression in order to decrease the length and severity of the episode.
OBJECTIVES
To determine the effectiveness and safety of the different existing treatments for first-episode genital herpes on the duration of symptoms and time to recurrence.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (from inception to April 2016), MEDLINE (from inception to April 2016), the Specialised Register of the Cochrane Sexually Transmitted Infections Review Group (from inception to April 2016), EMBASE (from inception to April 2016), PsycINFO (from inception to April 2016), CINAHL (from inception to April 2016), LILACS (from inception to April 2016), AMED (from inception to April 2016), and the Alternative Medicines Specialised Register (from inception to April 2016). We handsearched a number of relevant journals, searched reference lists of all included studies, databases of ongoing trials, and other Internet databases.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) on participants with first-episode genital herpes. We excluded vaccination trials, and trials in which the primary objective assessed a complication of HSV infection.
DATA COLLECTION AND ANALYSIS
All studies written in English were independently assessed by at least two review authors for inclusion, risk of bias for each trial, and to extract data. Studies requiring translation were assessed for inclusion, trial quality, and data extraction by external translators.
MAIN RESULTS
We included 26 trials with 2084 participants analysed. Most of the studies were conducted in the United Kingdom (UK) and United States (US), and involved men and women experiencing their first episode of genital herpes, with the exception of three studies which included only women. We rated the majority of these studies as having an unclear risk of bias; largely due to lack of information supplied in the publications, and due to the age of the trials. This review found low quality evidence from two studies of oral acyclovir, when compared to placebo, reduced the duration of symptoms in individuals undergoing their first episode of genital herpes (mean difference (MD) -3.22, 95% confidence interval (CI) -5.91 to -0.54; I(2) = 52%). In two studies (112 participants), intravenous acyclovir decreased the median number of days that patients with first-episode herpes suffered symptoms. Oral valaciclovir (converted to acyclovir) also showed a similar length of symptom duration when compared to acyclovir in two studies.There is currently no evidence that topical acyclovir reduces symptoms (MD -0.61 days, 95% CI -2.16 to 0.95; 3 RCTs, 195 participants, I(2) statistic = 56%). There is also no current evidence that the topical treatments of cicloxolone cream, carbenoxolone sodium cream, adenosine arabinoside, idoxuridine in dimethyl sulfoxide, when compared to placebo reduced the duration of symptoms in people undergoing their first episode of herpes.Two studies reported no evidence of a reduction in the number of median days to recurrence following treatment with oral acyclovir versus placebo. Adverse events were generally poorly reported by all of the included studies and we were unable to quantitatively analyse this outcome. For those taking acyclovir, there were no serious adverse events; the most common adverse events reported for oral acyclovir were coryza, dizziness, tiredness, diarrhoea and renal colic. For intravenous acyclovir these were phlebitis, nausea and abnormal liver function tests and for topical acyclovir there was pain with the topical application.Those undergoing interferon treatment had significantly more adverse events compared to those taking placebo.
AUTHORS' CONCLUSIONS
There is low quality evidence from this review that oral acyclovir reduced the duration of symptoms for genital herpes. However, there is low quality evidence which did not show that topical antivirals reduced symptom duration for patients undergoing their first episode of genital herpes. This review was limited by the inclusion of skewed data, resulting in few trials that we were able to meta-analyse.
Topics: Acyclovir; Administration, Oral; Antiviral Agents; Female; Herpes Genitalis; Humans; Injections, Intravenous; Male; Randomized Controlled Trials as Topic; Recurrence; Valacyclovir; Valine
PubMed: 27575957
DOI: 10.1002/14651858.CD010684.pub2 -
American Journal of Transplantation :... Mar 2017The role of antiviral prophylaxis for the prevention of posttransplant lymphoproliferative disease (PTLD) remains controversial for solid organ transplantation (SOT)... (Meta-Analysis)
Meta-Analysis Review
The Role of Antiviral Prophylaxis for the Prevention of Epstein-Barr Virus-Associated Posttransplant Lymphoproliferative Disease in Solid Organ Transplant Recipients: A Systematic Review.
The role of antiviral prophylaxis for the prevention of posttransplant lymphoproliferative disease (PTLD) remains controversial for solid organ transplantation (SOT) recipients who are seronegative for Epstein-Barr virus (EBV) but who received organs from seropositive donors. We performed a systematic review and meta-analysis to address this issue. Two independent assessors extracted data from studies after determining patient eligibility and completing quality assessments. Overall, 31 studies were identified and included in the quantitative synthesis. Nine studies were included in the direct comparisons (total 2366 participants), and 22 were included in the indirect analysis. There was no significant difference in the rate of EBV-associated PTLD in SOT recipients among those who received prophylaxis (acyclovir, valacyclovir, ganciclovir, valganciclovir) compared with those who did not receive prophylaxis (nine studies; risk ratio 0.95, 95% confidence interval 0.58-1.54). No significant differences were noted across all types of organ transplants, age groups, or antiviral use as prophylaxis or preemptive therapy. There was no significant heterogeneity in the effect of antiviral prophylaxis on the incidence of PTLD. In conclusion, the use of antiviral prophylaxis in high-risk EBV-naive patients has no effect on the incidence of PTLD in SOT recipients.
Topics: Antiviral Agents; Epstein-Barr Virus Infections; Herpesvirus 4, Human; Humans; Lymphoproliferative Disorders; Organ Transplantation; Premedication; Prognosis
PubMed: 27545492
DOI: 10.1111/ajt.14020 -
Canada Communicable Disease Report =... Feb 2016Among individuals with genital herpes simplex virus (HSV), co-infection with human immunodeficiency virus (HIV) has been shown to increase the frequency and severity of...
BACKGROUND
Among individuals with genital herpes simplex virus (HSV), co-infection with human immunodeficiency virus (HIV) has been shown to increase the frequency and severity of HSV symptoms, HSV shedding, and risk of HSV transmission.
OBJECTIVE
To assess whether suppressive antivirual therapy for genital HSV in an HIV-positive populatation prevents HSV transmission to a susceptible partner.
METHODS
A systematic search of the literature was conducted using MEDLINE and EMBASE databases to identify randomized controlled trials published between January 2005 and June 2015. Inclusion criteria were trials written in English or French utilizing suppressive antiviral therapies for HSV. Studies had to report on outcomes related to HSV transmission from HIV-positive populations. Surrogate markers of HSV transmission risk, such as HSV detection and viral load, were also included. Articles underwent a risk of bias assessment, and those with low risk of bias underwent data extraction to complete a narrative synthesis.
RESULTS
This review identified thirteen papers. Only one study directly measured transmission of HSV. The overall transmission rate was <10%, and suppressive antiviral therapy had no significant protective effect (9% transmission rate in the acyclovir group vs. 6% in the placebo group; hazard ratio [HR]: 1.35, 95% CI: 0.83-2.20). The remaining 12 papers addressed surrogate markers of transmission risk: HSV detection and viral load. Suppressive acyclovir appears to be effective in reducing HSV detection among HIV-positive populations, but it does not appear to reduce viral load. Suppressive valacyclovir may be effective in reducing HSV detection and viral load among HIV-positive patients who are antiretroviral therapy (ART)-naïve, but its effect appears to be nullified among those concurrently on ART.
CONCLUSION
Based on current evidence, suppressive antiviral therapy may reduce HSV detection and viral load, but its impact on HSV transmission is unclear. Clinicians should caution HIV-positive patients with HSV that suppressive therapy may not reduce risk of HSV transmission to susceptible partners.
PubMed: 29770002
DOI: 10.14745/ccdr.v42i02a03 -
The Cochrane Database of Systematic... Jan 2016The Cochrane Oral Health Group withdrew this review as of Issue 1, 2016. The review is out of date and does not meet current Cochrane methodological standards. It will... (Meta-Analysis)
Meta-Analysis Review
The Cochrane Oral Health Group withdrew this review as of Issue 1, 2016. The review is out of date and does not meet current Cochrane methodological standards. It will be superseded by a new expanded Cochrane review on Interventions for treating primary herpetic gingivostomatitis. The editorial group responsible for this previously published document have withdrawn it from publication.
Topics: Acyclovir; Antiviral Agents; Child; Child, Preschool; Female; Gingivitis; Humans; Infant; Male; Randomized Controlled Trials as Topic; Stomatitis, Herpetic
PubMed: 26784280
DOI: 10.1002/14651858.CD006700.pub3 -
The Cochrane Database of Systematic... Aug 2015Herpes simplex labialis (HSL), also known as cold sores, is a common disease of the lips caused by the herpes simplex virus, which is found throughout the world. It... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Herpes simplex labialis (HSL), also known as cold sores, is a common disease of the lips caused by the herpes simplex virus, which is found throughout the world. It presents as a painful vesicular eruption, forming unsightly crusts, which cause cosmetic disfigurement and psychosocial distress. There is no cure available, and it recurs periodically.
OBJECTIVES
To assess the effects of interventions for the prevention of HSL in people of all ages.
SEARCH METHODS
We searched the following databases up to 19 May 2015: the Cochrane Skin Group Specialised Register, the Oral Health Group Specialised Register, CENTRAL in the Cochrane Library (Issue 4, 2015), MEDLINE (from 1946), EMBASE (from 1974), LILACS (from 1982), the China National Knowledge Infrastructure (CNKI) database, Airiti Library, and 5 trial registers. To identify further references to relevant randomised controlled trials, we scanned the bibliographies of included studies and published reviews, and we also contacted the original researchers of our included studies.
SELECTION CRITERIA
Randomised controlled trials (RCTs) of interventions for preventing HSL in immunocompetent people.
DATA COLLECTION AND ANALYSIS
Two authors independently selected trials, extracted data, and assessed the risk of bias. A third author was available for resolving differences of opinion.
MAIN RESULTS
This review included 32 RCTs, with a total of 2640 immunocompetent participants, covering 19 treatments. The quality of the body of evidence was low to moderate for most outcomes, but was very low for a few outcomes. Our primary outcomes were 'Incidence of HSL' and 'Adverse effects during use of the preventative intervention'.The evidence for short-term (≤ 1 month) use of oral aciclovir in preventing recurrent HSL was inconsistent across the doses used in the studies: 2 RCTs showed low quality evidence for a reduced recurrence of HSL with aciclovir 400 mg twice daily (risk ratio (RR) 0.26, 95% confidence interval (CI) 0.13 to 0.51; n = 177), while 1 RCT testing aciclovir 800 mg twice daily and 2 RCTs testing 200 mg 5 times daily found no similar preventive effects (RR 1.08, 95% CI 0.62 to 1.87; n = 237; moderate quality evidence and RR 0.46, 95% CI 0.20 to 1.07; n = 66; low quality evidence, respectively). The direction of intervention effect was unrelated to the risk of bias. The evidence from 1 RCT for the effect of short-term use of valaciclovir in reducing recurrence of HSL by clinical evaluation was uncertain (RR 0.55, 95% CI 0.23 to 1.28; n = 125; moderate quality evidence), as was the evidence from 1 RCT testing short-term use of famciclovir.Long-term (> 1 month) use of oral antiviral agents reduced the recurrence of HSL. There was low quality evidence from 1 RCT that long-term use of oral aciclovir reduced clinical recurrences (1.80 versus 0.85 episodes per participant per a 4-month period, P = 0.009) and virological recurrence (1.40 versus 0.40 episodes per participant per a 4-month period, P = 0.003). One RCT found long-term use of valaciclovir effective in reducing the incidence of HSL (with a decrease of 0.09 episodes per participant per month; n = 95). One RCT found that a long-term suppressive regimen of valaciclovir had a lower incidence of HSL than an episodic regimen of valciclovir (difference in means (MD) -0.10 episodes per participant per month, 95% CI -0.16 to -0.05; n = 120).These trials found no increase in adverse events associated with the use of oral antiviral agents (moderate quality evidence).There was no evidence to show that short-term use of topical antiviral agents prevented recurrent HSL. There was moderate quality evidence from 2 RCTs that topical aciclovir 5% cream probably has little effect on preventing recurrence of HSL (pooled RR 0.91, 95% CI 0.48 to 1.72; n = 271). There was moderate quality evidence from a single RCT that topical foscarnet 3% cream has little effect in preventing HSL (RR 1.08, 95% CI 0.82 to 1.40; n = 295).The efficacy of long-term use of topical aciclovir cream was uncertain. One RCT found significantly fewer research-diagnosed recurrences of HSL when on aciclovir cream treatment than on placebo (P < 0.05), but found no significant differences in the mean number of participant-reported recurrences between the 2 groups (P ≥ 0.05). One RCT found no preventive effect of topical application of 1,5-pentanediol gel for 26 weeks (P > 0.05). Another RCT found that the group who used 2-hydroxypropyl-β-cyclo dextrin 20% gel for 6 months had significantly more recurrences than the placebo group (P = 0.003).These studies found no increase in adverse events related to the use of topical antiviral agents.Two RCTs found that the application of sunscreen significantly prevented recurrent HSL induced by experimental ultraviolet light (pooled RR 0.07, 95% CI 0.01 to 0.33; n = 111), but another RCT found that sunscreen did not prevent HSL induced by sunlight (RR 1.13, 95% CI 0.25 to 5.06; n = 51). These RCTs did not report adverse events.There were very few data suggesting that thymopentin, low-level laser therapy, and hypnotherapy are effective in preventing recurrent HSL, with one to two RCTs for each intervention. We failed to find any evidence of efficacy for lysine, LongoVital® supplementation, gamma globulin, herpes simplex virus (HSV) type I subunit vaccine, and yellow fever vaccine in preventing HSL. There were no consistent data supporting the efficacy of levamisole and interferon, which were also associated with an increased risk of adverse effects such as fever.
AUTHORS' CONCLUSIONS
The current evidence demonstrates that long-term use of oral antiviral agents can prevent HSL, but the clinical benefit is small. We did not find evidence of an increased risk of adverse events. On the other hand, the evidence on topical antiviral agents and other interventions either showed no efficacy or could not confirm their efficacy in preventing HSL.
Topics: Antiviral Agents; Herpes Labialis; Humans; Randomized Controlled Trials as Topic; Recurrence; Secondary Prevention
PubMed: 26252373
DOI: 10.1002/14651858.CD010095.pub2 -
Anais Da Academia Brasileira de Ciencias Aug 2015We performed a systematic review with the objective of verifying the efficacy of topical use 5% Acyclovir-1% Hydrocortisone cream compared to the placebo group for... (Review)
Review
We performed a systematic review with the objective of verifying the efficacy of topical use 5% Acyclovir-1% Hydrocortisone cream compared to the placebo group for herpes simplex labialis treatment. We performed a literature search using MEDLINE, Embase, BIOSIS, LILACS, Scopus, Grey literature, the Cochrane Central Register of Controlled Trials, the ISI Web of Science and IBECS from 1990 to June 2014. We reported the outcomes using relative risk (RR) with 95% confidence intervals. The literature search yielded 180 potentially relevant publications. Reviews of the reference lists yielded two further citations. Among these papers, two were considered eligible for inclusion in this review. Both trials included 1,213 patients. A meta-analysis of these studies showed a RR = 0.77, (95% CI 0.70-0.86; p<0.001).This result suggests that an early episodic treatment with the combination of an antiviral and a steroid is beneficial for herpes simplex labialis treatment.
Topics: Acyclovir; Administration, Topical; Anti-Inflammatory Agents; Antiviral Agents; Drug Combinations; Herpes Labialis; Humans; Hydrocortisone; Randomized Controlled Trials as Topic
PubMed: 26247156
DOI: 10.1590/0001-3765201520140701