Treatment of Cold Sores Caused by HSV-2
Important Clinical Clarification
Cold sores are typically caused by HSV-1, not HSV-2—genital herpes is the most common manifestation of HSV-2 infection. 1 If you are seeing oral lesions and suspect HSV-2, laboratory confirmation with viral typing is essential, as HSV-1 and HSV-2 orolabial infections are clinically indistinguishable but have different recurrence patterns. 1
Diagnostic Approach
Laboratory diagnosis should be pursued in all cases of suspected HSV infection, as clinical diagnosis alone has poor sensitivity and specificity. 1
- PCR is the most sensitive diagnostic method for detecting HSV from mucosal lesions, though it is not widely available. 1
- Viral culture and HSV antigen detection are alternative diagnostic methods. 1
- The virus detected should be typed (HSV-1 vs HSV-2) because this affects prognosis—HSV-1 recurs less frequently than HSV-2 in both oral and genital locations. 1
- Type-specific serologic assays can be used in asymptomatic persons or those with atypical lesions. 1
Treatment for Orolabial HSV-2 (If Confirmed)
First-Line Antiviral Therapy
For orolabial HSV infections in immunocompetent adults, treat with oral antiviral therapy for 7-10 days. 2 While specific dosing for orolabial HSV-2 is not separately defined in guidelines, the treatment approach mirrors that for HSV-1 orolabial disease:
- Famciclovir 1500 mg as a single dose is FDA-approved for recurrent herpes labialis (cold sores) and should be initiated at the first sign of symptoms. 3
- Valacyclovir 500 mg twice daily for 5 days is an alternative option for recurrent episodes. 2
- Acyclovir 400 mg three times daily for 5 days or acyclovir 800 mg twice daily for 5 days are additional options. 2
Treatment Timing
- Episodic therapy is most effective when started during the prodromal period or within 1 day after onset of lesions. 2
- Delayed treatment beyond 72 hours significantly reduces effectiveness. 2
HIV-Infected Patients
For HIV-infected patients with orolabial HSV-2, use famciclovir 500 mg twice daily for 7 days. 3 This longer course is necessary because:
- HIV-infected patients may require longer therapy than HIV-negative patients. 1
- In profoundly immunocompromised patients (CD4+ <100 cells/µL), extensive, deep, nonhealing ulcerations may occur. 1
Suppressive Therapy Considerations
For patients with frequent recurrences (≥6 episodes per year), daily suppressive therapy should be considered:
Valacyclovir 500 mg to 1 g orally once daily 2
Acyclovir 400 mg orally twice daily 2
Suppressive therapy can reduce recurrence frequency by ≥75% and reduce asymptomatic viral shedding. 2
After 1 year of suppressive therapy, consider discontinuation to reassess recurrence frequency. 2
Renal Dosing Adjustments
For patients with renal impairment, dose adjustments are mandatory to prevent acute renal failure. 3 Consult the famciclovir prescribing information for specific creatinine clearance-based dosing. 3
Treatment Failure
If lesions do not begin to resolve within 7-10 days of appropriately dosed antiviral therapy, suspect acyclovir resistance:
- Obtain viral culture of the lesion and perform susceptibility testing. 2
- Acyclovir resistance is more commonly associated with immunocompromised patients. 1
- For confirmed acyclovir-resistant HSV, IV foscarnet 40 mg/kg every 8 hours is the treatment of choice. 2
Critical Counseling Points
- Topical acyclovir is substantially less effective than systemic therapy and is not recommended. 2
- Systemic antiviral drugs partially control symptoms but do not eradicate latent virus or affect subsequent recurrences after discontinuation. 2
- Patients should be counseled about transmission risk and advised to abstain from sexual activity when lesions or prodromal symptoms are present. 2
- Consistent condom use should be encouraged to reduce HSV-2 transmission. 2
- HSV-2 is a risk factor for HIV acquisition, and HSV-2 reactivation results in increases in HIV RNA levels in coinfected patients. 1