In a healthy adult with acute herpes simplex virus infection, how soon after initiating oral antiviral therapy (e.g., acyclovir, valacyclovir, famciclovir) can clinical improvement and lesion healing be expected?

Timeframe for Response to Antiviral Therapy in Acute HSV Infection

In healthy adults with acute herpes simplex virus infection, clinical improvement typically begins within 24–48 hours of initiating oral antiviral therapy, with complete lesion healing occurring in 4–6 days for treated episodes compared to 6–8 days without treatment. 1, 2

Expected Clinical Response Timeline

Early Response (First 24–48 Hours)

• Viral shedding begins to decline within the first 24 hours of starting oral acyclovir, valacyclovir, or famciclovir, representing the earliest measurable antiviral effect 3
• Patients should notice subjective improvement in symptoms (reduced pain, burning, tingling) within 1.7–3.3 days when treatment is initiated early 2
• Peak viral titers occur in the first 24 hours after lesion onset, making early treatment initiation critical for optimal response 1

Lesion Healing Timeline

• For herpes labialis (cold sores) treated with famciclovir 1500 mg single dose, median time to healing is 4.4 days compared to 6.2 days with placebo—a reduction of approximately 1.3 days 2
• For recurrent genital herpes treated with famciclovir 1000 mg twice daily for one day, median healing time is 4.3 days versus 6.1 days with placebo 2
• Complete crusting and healing of lesions typically occurs within 5–7 days when oral antivirals are started within 48 hours of symptom onset 3

Symptom Resolution

• Loss of pain and tenderness occurs at a median of 1.7 days with famciclovir versus 2.9 days with placebo for herpes labialis 2
• Complete resolution of all symptoms (tingling, itching, burning, pain) occurs at a median of 3.3 days with treatment compared to 5.4 days without 2

Critical Factors Affecting Response Time

Timing of Treatment Initiation

• Treatment must be initiated during the prodromal phase or within 24 hours of lesion appearance to achieve maximal benefit, as peak viral replication occurs in the first 24 hours 1
• Starting treatment within 48 hours is significantly more effective than delayed initiation, with shorter viral shedding duration and faster lesion healing 3
• Efficacy decreases markedly when treatment begins after the first 24–48 hours, though some benefit may still occur 1

Patient-Initiated Therapy

• Self-initiated episodic therapy at the earliest sign of symptoms may prevent lesion development entirely in some cases, with 23–33% of patients experiencing aborted lesions (not progressing beyond erythema or papule stage) 2, 1
• Providing patients with a prescription to keep on hand enables immediate treatment initiation, maximizing therapeutic benefit 1

Special Populations and Delayed Healing

Immunocompromised Patients

• Episodes are typically longer and more severe in immunocompromised hosts, potentially involving extensive oral cavity involvement or facial spread 1
• These patients may require higher doses or longer treatment durations and have a 7% rate of acyclovir resistance compared to <0.5% in immunocompetent hosts 1, 4
• Standard oral therapy should be initiated at 200 mg five times daily for 3–5 days; if response is poor, increase to 800 mg five times daily 4

Treatment Failure Recognition

• If no clinical improvement is seen after 5–7 days of oral therapy, resistance should be suspected and alternative regimens (foscarnet 40 mg/kg IV three times daily) considered 4
• Repeat cultures for viral, fungal, and bacterial pathogens should be obtained, along with acyclovir susceptibility testing if available 4

Common Pitfalls to Avoid

• Delaying treatment initiation beyond 24–48 hours significantly reduces efficacy, as the narrow therapeutic window for blocking viral replication is missed 1
• Relying on topical antivirals instead of oral therapy provides only modest benefit and is substantially less effective 1
• Failing to counsel patients about trigger avoidance (UV light, stress, fever) even during treatment 1
• Not providing patients with standby prescriptions for immediate self-initiation at first symptoms 1

Monitoring and Follow-Up

• Patients should expect noticeable symptom improvement within 24–48 hours and complete healing within 5–7 days 2, 3
• If lesions worsen or fail to improve after 5–7 days, suspect treatment failure or resistance and consider alternative diagnoses or therapies 4
• Viral shedding continues for approximately 6.4 days with valacyclovir treatment (versus 8.1 days without), so patients remain contagious until all lesions are fully crusted 1