What is the recommended diagnosis and management of herpes simplex virus type 1 infection in adults?

HSV-1 Infection: Diagnosis and Management

Diagnosis

Laboratory confirmation is essential for all suspected HSV-1 infections, as clinical diagnosis alone is unreliable, particularly in immunocompromised patients. 1

Diagnostic Testing Approach

For symptomatic patients with active lesions:

• PCR is the most sensitive diagnostic method and should be the first-line test when available 1
• Viral culture from vesicular fluid remains effective—collect by opening vesicles with a sterile needle and swabbing the fluid 1, 2
• HSV antigen detection (direct immunofluorescence or enzyme immunoassay) can be used if PCR or culture are unavailable, but viral typing is essential 1
• All genital lesions must be typed to distinguish HSV-1 from HSV-2, as this critically impacts prognosis and counseling 1

For asymptomatic individuals or atypical presentations:

• Type-specific serologic assays are commercially available and appropriate for asymptomatic screening in select populations 1
• Serology should be considered for pregnant women at risk of acquiring HSV near delivery, men who have sex with men, and HIV-positive individuals 1
• Widespread screening for HSV antibodies in the general population should be discouraged 1

Common Diagnostic Pitfalls

• Avoid relying on clinical appearance alone—HSV-1 can cause both oral and genital lesions due to oral-genital sexual practices 1
• In immunocompromised patients (CD4+ <100 cells/µL), lesions may be extensive, deep, and non-healing, potentially harboring acyclovir-resistant virus 1

Clinical Manifestations

Orolabial HSV-1 (Most Common Presentation)

Orolabial herpes is the most common manifestation of HSV-1 infection 1, 3

• Classic presentation includes sensory prodrome followed by lesion evolution: papule → vesicle → ulcer → crust on the lips 1
• Untreated course lasts 7-10 days 1
• Recurrences occur 1-12 times per year, triggered by sunlight or physiologic stress 1
• Primary herpetic gingivostomatitis affects tongue, lips, gingiva, buccal mucosa, and hard/soft palate 4

Genital HSV-1

Genital HSV-1 infection is clinically indistinguishable from HSV-2 during acute episodes but recurs significantly less frequently 1

• Genital HSV-1 recurs at approximately 1.3 episodes/year in the first year, decreasing to 0.7/year in the second year 5
• 43% of patients have no recurrence in the first year; 67% have no recurrence in the second year 5
• This markedly better prognosis compared to HSV-2 makes viral typing essential for accurate patient counseling 5

Severe/Atypical Presentations

• HSV keratitis, encephalitis, hepatitis, and herpetic whitlow occur similarly in HIV-negative persons 1
• HSV-2 meningitis requires distinction from HSV encephalitis—meningitis presents with headache, photophobia, fever, CSF lymphocytic pleocytosis with mildly elevated protein and normal glucose 1
• For first-episode HSV-2 meningitis: acyclovir 10 mg/kg IV every 8 hours until fever/headache resolve, then valacyclovir 1g TID to complete 14 days 1
• HSV encephalitis requires 14-21 days of IV acyclovir due to high morbidity and mortality 1

Management

Orolabial HSV-1

Systemic antiviral therapy is widely accepted as effective for primary herpetic gingivostomatitis 6

• Acyclovir 5% cream is the accepted standard topical therapy for herpes labialis, being both effective and well-tolerated 6
• Penciclovir 1% cream is a potentially useful alternative 6
• Systemic acyclovir may reduce symptom duration in recurrent infection, though optimal timing and dose remain uncertain 6

Genital HSV-1

Treatment efficacy is expected to be equivalent between HSV-1 and HSV-2 based on viral biology and in vitro susceptibilities 1

• Episodic therapy or suppressive therapy can be used, though suppressive therapy is less commonly needed given the low recurrence rate 1
• Suppressive therapy (valacyclovir 500 mg daily) should be considered only for patients with frequent recurrences 1

Immunocompromised Patients

Acyclovir and famciclovir are beneficial for acute treatment of severe HSV-1 disease in immunocompromised patients 6

• Prophylactic oral acyclovir reduces frequency and severity of recurrent attacks, though optimal timing and duration vary by situation 6
• Monitor for acyclovir-resistant virus in patients with CD4+ <100 cells/µL who develop non-healing ulcerations 1

Transmission Prevention

Consistent latex condom use reduces HSV-2 transmission risk, and this protection likely extends to HSV-1 genital transmission 1, 3

• Avoid all sexual contact when visible orolabial or genital lesions are present 1, 3
• Asymptomatic viral shedding occurs frequently—HSV-1 was detected on 26.5% of days in seropositive adults, with 27.1% of shedding occurring on asymptomatic days 7
• Oral shedding is widespread throughout the oral cavity and may increase transmission risk to both oral and genital mucosa of sexual partners 7
• HSV-1 is rarely found in tears and nasal mucosa 7

Key Counseling Points

• Most HSV-1 infections are unrecognized clinically, yet intermittent mucosal reactivation can result in transmission 1
• Genital HSV-1 has a significantly better prognosis than genital HSV-2, with lower recurrence rates 5
• Transmission can occur during asymptomatic periods through viral shedding 1, 7
• HSV-2 (and likely HSV-1) increases HIV acquisition risk approximately 3-fold 1, 3