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Journal of Infection and Public Health Oct 2023Dengue is caused by the dengue virus (DENVs) infection and clinical manifestations include dengue fever (DF), dengue hemorrhagic fever (DHF), or dengue shock syndrome...
Dengue is caused by the dengue virus (DENVs) infection and clinical manifestations include dengue fever (DF), dengue hemorrhagic fever (DHF), or dengue shock syndrome (DSS). Due to a lack of antiviral drugs and effective vaccines, several therapeutic and control strategies have been proposed. A systemic literature review was conducted according to PRISMA guidelines to select proper references to give an overview of DENV infection. Results indicate that understanding the virus characteristics and epidemiology are essential to gain the basic and clinical knowledge as well as dengue disseminated pattern and status. Different factors and mechanisms are thought to be involved in the presentation of DHF and DSS, including antibody-dependent enhancement, immune dysregulation, viral virulence, host genetic susceptibility, and preexisting dengue antibodies. This study suggests that dissecting pathogenesis and risk factors as well as developing different types of therapeutic and control strategies against DENV infection are urgently needed.
Topics: Humans; Antiviral Agents; Dengue; Genetic Predisposition to Disease; Risk Factors; Virulence
PubMed: 37595484
DOI: 10.1016/j.jiph.2023.08.001 -
JAMA Network Open Aug 2021Antiviral treatment of influenza is recommended for patients with influenza-like illness during periods of community cocirculation of influenza viruses and SARS-CoV-2;... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Antiviral treatment of influenza is recommended for patients with influenza-like illness during periods of community cocirculation of influenza viruses and SARS-CoV-2; however, questions remain about which treatment is associated with the best outcomes and fewest adverse events.
OBJECTIVE
To compare the efficacy and safety of neuraminidase inhibitors and the endonuclease inhibitor for the treatment of seasonal influenza among healthy adults and children.
DATA SOURCES
Medline, Embase, and the Cochrane Register of Clinical Trials were searched from inception to January 2020 (the last search was updated in October 2020).
STUDY SELECTION
Included studies were randomized clinical trials conducted among patients of all ages with influenza treated with neuraminidase inhibitors (ie, oseltamivir, peramivir, zanamivir, or laninamivir) or an endonuclease inhibitor (ie, baloxavir) compared with other active agents or placebo.
DATA EXTRACTION AND SYNTHESIS
Two investigators identified studies and independently abstracted data. Frequentist network meta-analyses were performed; relative ranking of agents was conducted using P-score probabilities. Quality of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluations criteria. Data were analyzed in October 2020.
MAIN OUTCOMES AND MEASURES
The time to alleviation of influenza symptoms (TTAS), complications of influenza, and adverse events (total adverse events, nausea, and vomiting).
RESULTS
A total of 26 trials were identified that investigated antiviral drugs at high or low doses; these trials included 11 897 participants, among whom 6294 (52.9%) were men and the mean (SD) age was 32.5 (16.9) years. Of all treatments comparing with placebo in efficacy outcomes, high-quality evidence indicated that zanamivir was associated with the shortest TTAS (hazard ratio, 0.67; 95% CI, 0.58-0.77), while baloxavir was associated with the lowest risk of influenza-related complications (risk ratio [RR], 0.51; 95% CI, 0.32-0.80) based on moderate-quality evidence. In safety outcomes, baloxavir was associated with the lowest risk of total adverse events (RR, 0.84; 95% CI, 0.74-0.96) compared with placebo based on moderate-quality evidence. There was no strong evidence of associations with risk of nausea or vomiting among all comparisons, except for 75 mg oseltamivir, which was associated with greater occurrence of nausea (RR, 1.82; 95% CI, 1.38-2.41) and vomiting (RR, 1.88; 95% CI, 1.47-2.41).
CONCLUSIONS AND RELEVANCE
In this systematic review and network meta-analysis, all 4 antiviral agents assessed were associated with shortening TTAS; zanamivir was associated with the shortest TTAS, and baloxavir was associated with reduced rate of influenza-related complications.
Topics: Adolescent; Adult; Antiviral Agents; Child; Dibenzothiepins; Endonucleases; Enzyme Inhibitors; Female; Humans; Influenza A virus; Influenza, Human; Male; Middle Aged; Morpholines; Network Meta-Analysis; Neuraminidase; Pyridones; Randomized Controlled Trials as Topic; Seasons; Triazines; Young Adult; Zanamivir
PubMed: 34387680
DOI: 10.1001/jamanetworkopen.2021.19151 -
Hepatology (Baltimore, Md.) Jan 2016Chronic hepatitis B viral (HBV) infection remains a significant global health problem. Evidence-based guidelines are needed to help providers determine when treatment... (Meta-Analysis)
Meta-Analysis Review
UNLABELLED
Chronic hepatitis B viral (HBV) infection remains a significant global health problem. Evidence-based guidelines are needed to help providers determine when treatment should be initiated, which medication is most appropriate, and when treatment can safely be stopped. The American Association for the Study of Liver Diseases HBV guideline methodology and writing committees developed a protocol a priori for this systematic review. We searched multiple databases for randomized controlled trials and controlled observational studies that enrolled adults ≥18 years old diagnosed with chronic HBV infection who received antiviral therapy. Data extraction was done by pairs of independent reviewers. We included 73 studies, of which 59 (15 randomized controlled trials and 44 observational studies) reported clinical outcomes. Moderate-quality evidence supported the effectiveness of antiviral therapy in patients with immune active chronic HBV infection in reducing the risk of cirrhosis, decompensated liver disease, and hepatocellular carcinoma. In immune tolerant patients, moderate-quality evidence supports improved intermediate outcomes with antiviral therapy. Only very low-quality evidence informed the questions about discontinuing versus continuing antiviral therapy in hepatitis B e antigen-positive patients who seroconverted from hepatitis B e antigen to hepatitis B e antibody and about the safety of entecavir versus tenofovir. Noncomparative and indirect evidence was available for questions about stopping versus continuing antiviral therapy in hepatitis B e antigen-negative patients, monotherapy versus adding a second agent in patients with persistent viremia during treatment, and the effectiveness of antivirals in compensated cirrhosis with low-level viremia.
CONCLUSION
Most of the current literature focuses on the immune active phases of chronic HBV infection; decision-making in other commonly encountered and challenging clinical settings depends on indirect evidence.
Topics: Adult; Antiviral Agents; Hepatitis B e Antigens; Hepatitis B, Chronic; Humans; Liver Cirrhosis
PubMed: 26566246
DOI: 10.1002/hep.28280 -
Safety and Efficacy of Long-Acting Injectable Agents for HIV-1: Systematic Review and Meta-Analysis.JMIR Public Health and Surveillance Jul 2023HIV-1 infection continues to affect global health. Although antiretrovirals can reduce the viral load or prevent HIV-1 infection, current drugs require daily oral use... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
HIV-1 infection continues to affect global health. Although antiretrovirals can reduce the viral load or prevent HIV-1 infection, current drugs require daily oral use with a high adherence level. Long-acting antiretrovirals (LA-ARVs) significantly improve medication adherence and are essential for HIV-1 prophylaxis and therapy.
OBJECTIVE
This study aimed to investigate the safety and efficacy of long-acting cabotegravir (CAB-LA) and long-acting rilpivirine (RPV-LA) in the prevention and treatment of HIV-1 infection.
METHODS
PubMed, Embase, and the Cochrane Library were searched for studies from database inception to November 12, 2022. We included studies that reported efficacy and safety data on LA-ARV intervention in people living with HIV and excluded reviews, animal studies, and articles with missing or duplicate data. Virological suppression was defined as plasma viral load <50 copies/mL 6 months after antiviral therapy initiation. We extracted outcomes for analysis and expressed dichotomous data as risk ratios (RRs) and continuous data as mean differences. Depending on the heterogeneity assessment, a fixed- or random-effects model was used for data synthesis. We performed subgroup analyses of the partial safety and efficacy outcomes of CAB-LA+RPV-LA. The protocol was registered with the Open Science Framework.
RESULTS
We included 12 trials comprising 10,957 individuals, of which 7 were prevention trials and 5 were treatment trials. CAB-LA and RPV-LA demonstrated safety profiles comparable with those of the placebo in terms of adverse event-related withdrawal. Moreover, the efficacy data showed that CAB-LA had a better effect on HIV-1 prevention than tenofovir disoproxil fumarate-emtricitabine (17/5161, 0.33% vs 75/5129, 1.46%; RR 0.21, 95% CI 0.07-0.61; I=70%). Although CAB-LA+RPV-LA had more drug-related adverse events (556/681, 81.6% vs 37/598, 6.2%; RR 12.50, 95% CI 3.98-39.23; I=85%), a mild or moderate injection site reaction was the most common reaction, and its frequency decreased over time. The efficacy of CAB-LA+RPV-LA was comparable with that of daily oral drugs at 48 and 96 weeks (1302/1424, 91.43% vs 915/993, 92.2%; RR 0.99, 95% CI 0.97-1.02; I=0%), and a high level of virological suppression of 80.9% (186/230) was maintained even after 5 years of LA-ARV use. Similar efficacy outcomes were observed in both treatment-naive and treatment-experienced patients (849/911, 93.2% vs 615/654, 94%; RR 0.99, 95% CI 0.96-1.02; I=0%). According to the questionnaires, more than 85% of people living with HIV favored LA-ARVs.
CONCLUSIONS
LA-ARVs showed favorable safety profiles for both the prevention and treatment of HIV-1 infection and were well tolerated. CAB-LA has more satisfactory efficacy than tenofovir disoproxil fumarate-emtricitabine, significantly reducing the rate of HIV-1 infection. CAB-LA+RPV-LA maintains virological suppression for a long time and may be a viable switching strategy with enhanced public health benefits by reducing transmission. However, further trials are required to confirm the efficacy of these drugs.
Topics: Humans; Anti-HIV Agents; Emtricitabine; HIV Infections; HIV-1; Tenofovir
PubMed: 37498645
DOI: 10.2196/46767 -
The Journal of Antibiotics Sep 2020Ivermectin proposes many potentials effects to treat a range of diseases, with its antimicrobial, antiviral, and anti-cancer properties as a wonder drug. It is highly...
Ivermectin proposes many potentials effects to treat a range of diseases, with its antimicrobial, antiviral, and anti-cancer properties as a wonder drug. It is highly effective against many microorganisms including some viruses. In this comprehensive systematic review, antiviral effects of ivermectin are summarized including in vitro and in vivo studies over the past 50 years. Several studies reported antiviral effects of ivermectin on RNA viruses such as Zika, dengue, yellow fever, West Nile, Hendra, Newcastle, Venezuelan equine encephalitis, chikungunya, Semliki Forest, Sindbis, Avian influenza A, Porcine Reproductive and Respiratory Syndrome, Human immunodeficiency virus type 1, and severe acute respiratory syndrome coronavirus 2. Furthermore, there are some studies showing antiviral effects of ivermectin against DNA viruses such as Equine herpes type 1, BK polyomavirus, pseudorabies, porcine circovirus 2, and bovine herpesvirus 1. Ivermectin plays a role in several biological mechanisms, therefore it could serve as a potential candidate in the treatment of a wide range of viruses including COVID-19 as well as other types of positive-sense single-stranded RNA viruses. In vivo studies of animal models revealed a broad range of antiviral effects of ivermectin, however, clinical trials are necessary to appraise the potential efficacy of ivermectin in clinical setting.
Topics: Animals; Antiviral Agents; Betacoronavirus; Cell Line; DNA Viruses; Disease Models, Animal; Global Health; Humans; Ivermectin; Molecular Structure; RNA Viruses; SARS-CoV-2
PubMed: 32533071
DOI: 10.1038/s41429-020-0336-z -
The Lancet. Infectious Diseases Jan 2021To eliminate mother-to-child transmission (MTCT) of hepatitis B virus (HBV), peripartum antiviral prophylaxis might be required for pregnant women infected with HBV who... (Meta-Analysis)
Meta-Analysis
BACKGROUND
To eliminate mother-to-child transmission (MTCT) of hepatitis B virus (HBV), peripartum antiviral prophylaxis might be required for pregnant women infected with HBV who have a high risk of MTCT despite infant immunoprophylaxis. We aimed to determine the efficacy and safety of peripartum antiviral prophylaxis to inform the 2020 WHO guidelines.
METHODS
In this systematic review and meta-analysis, we searched PubMed, Embase, Scopus, CENTRAL, CNKI, and Wanfang for randomised controlled trials and non-randomised studies of peripartum antiviral prophylaxis versus placebo or no prophylaxis, with no language restriction, published from database inception until March 28, 2019. We used search terms covering HBV, antiviral therapy, and pregnancy. We included studies that enrolled pregnant women with chronic infection with HBV who received antiviral prophylaxis anytime during pregnancy; that included any of the following antivirals: adefovir, emtricitabine, entecavir, lamivudine, telbivudine, tenofovir alafenamide fumarate, and tenofovir disoproxil fumarate; and that reported the following outcomes: MTCT, indicated by infant HBsAg positivity or HBV DNA positivity, or both, at age 6-12 months, and any infant or maternal adverse events. Two reviewers independently extracted data. Our primary endpoint was MTCT based on infant HBsAg positivity. We assessed pooled odds ratios (ORs) of the efficacy of peripartum antiviral prophylaxis to reduce the risk of MTCT. We assessed safety of prophylaxis by pooling risk differences. The protocol for the systematic review was pre-registered in PROSPERO, CRD42019134614.
FINDINGS
Of 7463 articles identified, 595 articles were eligible for full-text review and 129 studies (in 157 articles) were included. The following antivirals were assessed in the meta-analysis: tenofovir disoproxil fumarate 300 mg (19 studies, with 1092 mothers and 1072 infants), lamivudine 100-150 mg (40 studies, with 2080 mothers and 2007 infants), and telbivudine 600 mg (83 studies, with 6036 mothers and 5971 infants). The pooled ORs for randomised controlled trials were similar, at 0·10 (95% CI 0·03-0·35) for tenofovir disoproxil fumarate, 0·16 (0·10-0·26) for lamivudine, and 0·14 (0·09-0·21) for telbivudine. The pooled ORs in non-randomised studies were 0·17 (0·10-0·29) for tenofovir disoproxil fumarate, 0·17 (0·12-0·24) for lamivudine, and 0·09 (0·06-0·12) for telbivudine. We found no increased risk of any infant or maternal safety outcomes after peripartum antiviral prophylaxis.
INTERPRETATION
Peripartum antiviral prophylaxis is highly effective at reducing the risk of HBV MTCT. Our findings support the 2020 WHO recommendation of administering antivirals during pregnancy, specifically tenofovir disoproxil fumarate, for the prevention of HBV MTCT.
FUNDING
World Health Organization.
Topics: Adult; Antiviral Agents; Female; Hepatitis B virus; Hepatitis B, Chronic; Humans; Infectious Disease Transmission, Vertical; Practice Guidelines as Topic; Pregnancy; Pregnancy Complications, Infectious; Prenatal Care; Tenofovir
PubMed: 32805200
DOI: 10.1016/S1473-3099(20)30586-7 -
CMAJ : Canadian Medical Association... Jul 2022Randomized trial evidence suggests that some antiviral drugs are effective in patients with COVID-19. However, the comparative effectiveness of antiviral drugs in... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Randomized trial evidence suggests that some antiviral drugs are effective in patients with COVID-19. However, the comparative effectiveness of antiviral drugs in nonsevere COVID-19 is unclear.
METHODS
We searched the Epistemonikos COVID-19 L·OVE (Living Overview of Evidence) database for randomized trials comparing antiviral treatments, standard care or placebo in adult patients with nonsevere COVID-19 up to Apr. 25, 2022. Reviewers extracted data and assessed risk of bias. We performed a frequentist network meta-analysis and assessed the certainty of evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach.
RESULTS
We identified 41 trials, which included 18 568 patients. Compared with standard care or placebo, molnupiravir and nirmatrelvir-ritonavir each reduced risk of death with moderate certainty (10.9 fewer deaths per 1000, 95% confidence interval [CI] 12.6 to 4.5 fewer for molnupiravir; 11.7 fewer deaths per 1000, 95% CI 13.1 fewer to 2.6 more). Compared with molnupiravir, nirmatrelvir-ritonavir probably reduced risk of hospital admission (27.8 fewer admissions per 1000, 95% CI 32.8 to 18.3 fewer; moderate certainty). Remdesivir probably has no effect on risk of death, but may reduce hospital admissions (39.1 fewer admissions per 1000, 95% CI 48.7 to 13.7 fewer; low certainty).
INTERPRETATION
Molnupiravir and nirmatrelvir-ritonavir probably reduce risk of hospital admissions and death among patients with nonsevere COVID-19. Nirmatrelvir-ritonavir is probably more effective than molnupiravir for reducing risk of hospital admissions. Most trials were conducted with unvaccinated patients, before the emergence of the Omicron variant; the effectiveness of these drugs must thus be tested among vaccinated patients and against newer variants.
Topics: Adult; Antiviral Agents; Humans; Network Meta-Analysis; Ritonavir; SARS-CoV-2; COVID-19 Drug Treatment
PubMed: 35878897
DOI: 10.1503/cmaj.220471 -
BMJ (Clinical Research Ed.) Jul 2020To compare the effects of treatments for coronavirus disease 2019 (covid-19). (Comparative Study)
Comparative Study
OBJECTIVE
To compare the effects of treatments for coronavirus disease 2019 (covid-19).
DESIGN
Living systematic review and network meta-analysis.
DATA SOURCES
WHO covid-19 database, a comprehensive multilingual source of global covid-19 literature, up to 3 December 2021 and six additional Chinese databases up to 20 February 2021. Studies identified as of 1 December 2021 were included in the analysis.
STUDY SELECTION
Randomised clinical trials in which people with suspected, probable, or confirmed covid-19 were randomised to drug treatment or to standard care or placebo. Pairs of reviewers independently screened potentially eligible articles.
METHODS
After duplicate data abstraction, a bayesian network meta-analysis was conducted. Risk of bias of the included studies was assessed using a modification of the Cochrane risk of bias 2.0 tool, and the certainty of the evidence using the grading of recommendations assessment, development, and evaluation (GRADE) approach. For each outcome, interventions were classified in groups from the most to the least beneficial or harmful following GRADE guidance.
RESULTS
463 trials enrolling 166 581 patients were included; 267 (57.7%) trials and 89 814 (53.9%) patients are new from the previous iteration; 265 (57.2%) trials evaluating treatments with at least 100 patients or 20 events met the threshold for inclusion in the analyses. Compared with standard care, three drugs reduced mortality in patients with mostly severe disease with at least moderate certainty: systemic corticosteroids (risk difference 23 fewer per 1000 patients, 95% credible interval 40 fewer to 7 fewer, moderate certainty), interleukin-6 receptor antagonists when given with corticosteroids (23 fewer per 1000, 36 fewer to 7 fewer, moderate certainty), and Janus kinase inhibitors (44 fewer per 1000, 64 fewer to 20 fewer, high certainty). Compared with standard care, two drugs probably reduce hospital admission in patients with non-severe disease: nirmatrelvir/ritonavir (36 fewer per 1000, 41 fewer to 26 fewer, moderate certainty) and molnupiravir (19 fewer per 1000, 29 fewer to 5 fewer, moderate certainty). Remdesivir may reduce hospital admission (29 fewer per 1000, 40 fewer to 6 fewer, low certainty). Only molnupiravir had at least moderate quality evidence of a reduction in time to symptom resolution (3.3 days fewer, 4.8 fewer to 1.6 fewer, moderate certainty); several others showed a possible benefit. Several drugs may increase the risk of adverse effects leading to drug discontinuation; hydroxychloroquine probably increases the risk of mechanical ventilation (moderate certainty).
CONCLUSION
Corticosteroids, interleukin-6 receptor antagonists, and Janus kinase inhibitors probably reduce mortality and confer other important benefits in patients with severe covid-19. Molnupiravir and nirmatrelvir/ritonavir probably reduce admission to hospital in patients with non-severe covid-19.
SYSTEMATIC REVIEW REGISTRATION
This review was not registered. The protocol is publicly available in the supplementary material.
READERS' NOTE
This article is a living systematic review that will be updated to reflect emerging evidence. Updates may occur for up to two years from the date of original publication. This is the fifth version of the original article published on 30 July 2020 (BMJ 2020;370:m2980), and previous versions can be found as data supplements. When citing this paper please consider adding the version number and date of access for clarity.
Topics: Adenosine Monophosphate; Alanine; Antiviral Agents; Betacoronavirus; COVID-19; Centers for Disease Control and Prevention, U.S.; China; Coronavirus Infections; Databases, Factual; Drug Combinations; Evidence-Based Medicine; Glucocorticoids; Humans; Hydroxychloroquine; Lopinavir; Network Meta-Analysis; Pandemics; Pneumonia, Viral; Randomized Controlled Trials as Topic; Respiration, Artificial; Ritonavir; SARS-CoV-2; Severity of Illness Index; Standard of Care; Treatment Outcome; United States; COVID-19 Drug Treatment
PubMed: 32732190
DOI: 10.1136/bmj.m2980 -
Viruses May 2019This manuscript aims to highlight all the clinical features of the herpes virus, with a particular focus on oral manifestations and in the maxillofacial district about...
This manuscript aims to highlight all the clinical features of the herpes virus, with a particular focus on oral manifestations and in the maxillofacial district about Herpes Simplex Virus-1 (HSV-1) and Herpes Simplex Virus-2 (HSV-2). Oral herpes virus is a very common and often debilitating infectious disease for patients, affecting oral health and having important psychological implications. The collection of relevant data comes from the scientific databases Pubmed, Embase; initially this collection obtained an extremely high number of results, 1415. After applying the inclusion and exclusion criteria, as well as a manual screening, the results included in this review were limited to 14. The results were expressed by evaluating all the signs and symptoms that this pathology entails during the study, paying attention to the characteristics linked to the quality of life and the psychological implications. This pathology has numerous therapies, which often make the healing phase of the manifestations of this viral pathology more comfortable. The therapies currently used for the treatment of this viral infection are pharmacological, topical, systemic, or instrumental, for example with laser devices.
Topics: Antiviral Agents; Herpesviridae; Herpesviridae Infections; Humans; Oral Health; Public Health Surveillance; Quality of Life; Randomized Controlled Trials as Topic; Symptom Assessment; Treatment Outcome
PubMed: 31117264
DOI: 10.3390/v11050463 -
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