Acyclovir resistance should be suspected in unresponsive cases .
Greatest experience in HSV treatment with this agent and only antiviral available in IV form. Data supports continuous use for suppression for up to 6 years without adverse effects or great risk of developing resistance (in normal hosts).
Topical gel, 1% may be used if resistant genital HSV identified. One application per day x 5 days should be sufficient to permit lesion healing, decrease symptoms and viral shedding. The preparation must be made by a compounding pharmacy as it is not commercially available. Injectable use usually only considered for refractory acyclovir-resistant cases not responsive to foscarnet.
Equivalent results to acyclovir when treating genital HSV. No data on adverse effects of long term suppression. Therefore, at 1 yr suppression should give pt a drug holiday and determine if sx recur.
Effective against thymidine kinase (TK)-deficient, drug-resistant HSV. Close monitoring of renal function and serum level of K+, Ca++, PO4-, and Mg++ required. Variable CNS penetration.
Prodrug of acyclovir. Advantage is less frequent dosing required. Equivalent results to acyclovir when treating genital HSV.
Comment: 2014 update of the 2007 guidelines on management of anogenital herpes, including management of genital herpes during pregnancy.
Comment: 2015 update of the 2010 CDC recommendations for treatment of sexually transmitted diseases.
Comment: Clinically useful overview with focus on neurological disease ranging from pregnancy/neonatal to adults.
Comment: Clear description and rationale for the recommendation for HSV management in pregnancy.
Comment: Review of 1028 infants who had HSV PCR peformed in blood and CSF speciments. Of the 21 who had positive CSF PCR, 76% also had positive HSV PCR in blood. The important conclusion is that a blood PCR in this population cannot be used to exclude CNS HSV infection.
Comment: This retrospective study analyzed 169 corneal swabs from 78 immunocompetent patients with recurrent herpetic keratitis for acyclovir resistance. Key findings: 1) 26% of the isolates were acyclovir resistant, 2) acyclovir prophylaxis x ≥12 m and recurrence duration of ≥45 days were associated with acyclovir resistance and acyclovir refractory disease, 3) acyclovir resistant isolates were a risk factor for acyclovir refractory disease (OR 2.28; 95% CI, 1.06–4.89).
Comment: This randomized controlled trial evaluated the impact of acyclovir 400mg twice daily on prevention of transmission of HSV-2 genital herpes in HIV-1/HSV-2 discordant couples in Africa. Key findings: Treatment of HSV-2/HIV-1-infected persons with daily suppressive acyclovir did not decrease risk of HSV-2 transmission to susceptible partners.
Comment: This was a retrospective, population-based case-control study of 114 patients with HSV ocular disease and 137 patients with herpes-zoster ocular disease (HZO) in Hawaii. Authors found that patients who had atopy had a 2.6-fold (95% CI, 1.6-4.2) higher odds of having HSVocular disease and 1.8-fold (95% CI, 1.2-2.8) increased odds of having HZO compared to patients without atopy. Patients with 2 or more atopic conditions had an 8.9-fold (95% CI, 3.5-22.6) higher odds of having HSVocular disease and a 2.9-fold (95% CI, 1.1-7.7) higher odds of having HZO.
Comment: This Sweedish randomized, double-blind, placebo-controlled multicenter trial investigated the effect of valacyclovir on prevention of recurrence of HSV meningitis. Patients received valacyclovir 500 mg twice daily (n=50) or placebo (n=51) for 1 year after primary or recurrent, confirmed or probable, HSV meningitis. Patients were followed for 2 years. Key finding: no difference between the 2 groups during the first year however during the second year, the risk of recurrence was higher among patients exposed to valacyclovir (HR, 3.29 [95% confidence interval, 10.06–10.21]).
Comment: A study of 74 infants with neonatal HSV: 45 with CNS involvement were enrolled in a study; 29 with skin, eye and mouth involvement (enrolled in a different study). All 45 neonates with CNS involvement received 14-21 d of parenteral acyclovir and then were randomly assigned to receive acyclovir suppression TID x 6 mo vs placebo. The Mental Development Index of the Bayley Scales of Infant Development (in which scores range from 50 to 150, with a mean of 100 and with higher scores indicating better neurodevelopmental outcomes) was assessed in 28 of the 45 infants with CNS involvement (62%) at 12 months of age. Infants surviving neonatal HSV disease with CNS involvement had significantly improved neurodevelopmental outcomes when they received suppressive therapy with oral acyclovir for 6 months.
Comment: This randomized, double-blind, placebo-controlled multicenter, multinational phase III clinical trial among HIV-uninfected, HSV-2 seropositive heterosexual women (n=1358) and men who have sex with men (MSM; n=1814) examined the primary outcome of new HIV-1 acquisition and the secondary outcome of the incidence of genital ulcers amongst those receiving twice daily acyclovir (400 mg) and placebo. Amongst participants from all countries no reduction in HIV-1 incidence was noted between the treatment and control groups. HSV-2 positive ulcers were reduced 63% in the treatment group compared with the control group (Relative risk = 0.37, Confidence Interval 0.31-0.45). No serious drug effects were noted in the study.
Comment: This was a prospective case-control study to examine immunogenetic risk factors for recurrent genital herpes. the study population included 52 eligible consecutive patients, without immunodeficiency, with culture-confirmed HSV-2 from an active lesion >12 months before enrollment and >9 recurrences per year and 80 HSV seropositive and 70 HSV seronegative controls. Anti-HSV-2 antibodies did not correlate with protection from recurrence. Risk factors for recurrence included lower levels of IgG1 antibody -Confidence Interval (CI), 2.0-12.5; p<0.001 and IgG3 antibody - CI 1.7-7,8, p<.001. Complement levels were lower in patients with recurrent symptomatic infection.
Comment: This Australian community-based cohort study of 1,427 HIV-negative gay men examined risk factors for herpes simplex virus type 1 (HSV-1) and HSV type 2 (HSV-2) over a median follow-up period of 2 years. At enrolment the prevalence of HSV-1 was 75% and HSV-2 was 23% and both infections had a lower prevalence in those <25 years. The incidence of HSV-1 infection was 5.58/100 person-years (PY) and 1.45/100 PY for HSV-2. Using multivariate analysis, significant independent risk factors for HSV-1 infection were insertive oral intercourse with casual sex partners (hazards ration = 3.91; 95% confidence interval [CI] =1.23-12.44) and younger age (p<0.03). Significant risk factor for HSV-2 acquisition was anal sex with casual partners.
Comment: This is the report of a 27-site multicenter randomized, double-blinded parallel placebo control trial examining the efficacy of a 1-gram dose of valacyclovir (VAC) in reducing HSV-2 viral shedding in both clinical and asymptomatic infections among immunocompetent persons. 152 persons were randomized--43 placebo (40 completed) and 109 VAC (94 completed. Over 60 day period each participant reported daily on presence or absence of genital lesions and collected daily genital and ano-rectal samples. VAC significantly decreased total days of viral shedding amongst both clinical and subclinical cases as well as viral load when shedding compared with the controls. In the intent to treat group, a 71% reduction in total shedding was noted (p<0.001), a 58% reduction in subclinical shedding (p<0.001), and a 64% reduction in clinical shedding (p<0.01) was seen in the VAC group. There were no major adverse effects noted with VAC over the 60-day study period.
Comment: This was a randomized, controlled Phase IIb trial of a 10 session behavioral intervention vs brief counseling session (control group) to reduce HIV acquisition among 4295 high-risk HIV-uninfected men who have sex with men (MSM). Sera and behavioral data collected during this trial were subsequently examined to determine risk factors for herpes simples virus type 2 (HSV-2, ) evaluate the role of prevalent and incident HSV-2 infection in HIV infection acquisition, and to determine the impact of the behavioral intervention on HSV acquisition (already shown not to have a role in HIV acquisition). 91% of subjects had evaluable data; 20.3% were HSV-2 positive (by serology) at enrolment; 4.3% acquired infection over the 24 month study period, and 75.4% remained uninfected with HSV-2. Risk factors for seroconversion included unprotected anal receptive intercourse in the prior 6 months, having at least 1 HIV-infected partner in the past 6 months, having >5 male sex partners in the last 6 months. HIV risk was increased among MSM with recent HSV-2 infection identified compared with HSV-2 uninfected MSM. Intense behavioral intervention did not increase the risk of HSV-2 infection.
Comment: Excellent review on RBLM.
Comment: The authors report the largest case series of 11 patients/12 eyes with HSV-2 acute retinal necrosis (ARN) and review the world's literature. Although other infections are associated with ARN, the authors identify some HSV-2 specific features including: young age at DX, hx of HSV at birth, preexisting chorioretinal scar in the ARN eye, triggering events such as trauma or steroids. Also, the clinical syndrome described with HSV-2 is more aggressive and rapid. This is a sight threatening condition and requires prompt consultative referral to an ophthalmologist.
Comment: The authors report the findings of a study among 89 pts with HSV-like lesions--81 with genital and 8 with cutaneous lesions. Specimens were collected for quantitative duplex PCR and culture; 64% were PCR positive; 51% were cx positive. PCR detected 30 of 34 primary and 24 of 29 recurrent infections. 2 HSV-1 samples were positive on cx only despite repeated PCR attempts. Symptomatic pts had significantly higher copy number on PCR. In this study, duplex qPCR for HSV-1 and HSV-2 was more sensitive than the gold standard cx for mucocutaneous HSV.
Comment: The authors carried out a study among 528 mutually-monogamous heterosexual couples discordant for HSV-2 infection. Although the antiviral was the intervention under observation, data were also collected re: condom use. When condoms were used more than 70% of the time by the discordant pairs with a positive man and a negative woman, transmission risk was reduced 60% even in the absence of antiviral suppression. Acquisition of infection by the seronegative partner and recurrence and shedding by the positive partner was significantly reduced when valacyclovir was used.
Comment: Report of a chart review of 170 patients seen on referral to a dermatology clinic found to have culture-confirmed HSV. This specialty practice was likely to see "outliers" in presentation as only 49% had "typical" cluster genital lesions. Single ulcers, erosion, crusts, fissures, edema, erythema were seen. Women were more likely to have extragenital lesions than were men.
Comment: Author reviewed 29 published clinical trials. Notable that ACV ointment did cause superficial punctate keratitis in 9.8% of 998 pts and 4% noted burning of the eye with application of agent. Found to compare favorably with other topical antiherpetics available.
Primary Herpes Simplex virus infection involving lips and tongue.
Ulcers and vesicle from genital HSV are seen around vaginal introitus due to HSV-2.
Vesicle seen on penile shaft due to HSV-2.
Source: CDC/Suan Lindsley
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