Evaluation of effectiveness and safety of acyclovir 1gm twice a day for treatment of recurrent genital herpes Kaushal Verma, M Sunane, Somesh Gupta All India Institute of Medical Sciences New Delhi, India Conflict of interest – None

Introduction ♦ Chronic relapsing disease, with recurrent genital vesicles/ painful erosions ♦ Sexual acquisition of HSV (HSV2>> HSV1) ♦ HSV maintains latent infection in nerve ganglion  recurrent episodes ♦ Recurrent rates usually declines with time ♦ Not a fatal disease

Why Treat !!! ♦ Lesions on important body sites ♦ Palliation and promotion of healing ♦ Reducing transmission ♦ Suppression of recurrences ♦ Abort or reduce the duration of episodes ♦ Prevention of complications

Challenges in management ♦ Lack of cure & unpredictable nature of recurrences ♦ Cost & compliance issue with suppressive therapy ♦ Communication & counseling issues ♦ Significant impact on Quality of life ♦ Grief reaction to diagnosis ♦ Sexual difficulties: fear of transmission impaired function ♦ Asymptomatic viral shedding ♦ Accounts for 70% of transmission ♦ Viral shedding occurs in 4-75% of days

Treatment of recurrent genital herpes ♦ Acyclovir mg five times a day ♦ Acyclovir mg three times a day ♦ Acyclovir mg two times a day ♦ Valacyclovir mg thrice a day ♦ Valacyclovir mg twice a day ♦ Valacyclovir mg once a day ♦ Famciclovir mg two times a day ( for 5-7 days or till complete healing) ♦ Famciclovir mg 2 times a day X 1 day (patient initiated)

Acyclovir ♦ Safe but poor oral bioavailability (10-20%) ♦ Short plasma t ½  frequent dosing Valacyclovir ♦ Valine ester prodrug of acyclovir: readily absorbed  5 times greater bioavailability ♦ Headache : most common side-effect ( %) ♦ ?? Thrombotic Microangiopathy (TMA) : Long term high dose therapy Famciclovir ♦ Diethyl ester form of penciclovir  Rapidly absorbed  greater bioavailability ♦ Safety profile comparable to acyclovir

Acyclovir, valacyclovir and famciclovir EQUALLY efficacious and safe in treatment of recurrent genital herpes Valacyclovir and famciclovir offer more convenient dosing regimens but expensive

Episodic treatment should start as early as possible since maximum viral replication occurs within 24 hours of the first prodrome symptom

We evaluated effectiveness and safety of oral acyclovir 1gm twice daily for 3 days in treatment of recurrent genital herpes

Patients’ profile No. of patients :22 Age range (mean) :18-55 yrs (28.95 ± 8.21) Male/female :20 : 2 Duration of disease : 0.1 to 204 months (mean ± 50.56) No. of recur / yr : 1-48 (mean ± 11.56)

Inclusion and exclusion criteria Inclusion: ♦ >16 years age, either sex with clinically active genital herpes Exclusion: ♦ Patients with severe renal, hepatic or heart disease ♦ Pregnant and lactating women ♦ Antiviral therapy within previous 14 days ♦ Immunosuppressed patients including transplant recipients on immunosuppressive drugs, HIV positive ♦ Known hypersensitivity to acyclovir ♦ Unwilling to consent for the study

Intervention and follow up Complete clinical and lab evaluation Acyclovir 1gm twice daily orally for 3 days Followed up on day 3, 5 and 7 ♦ Response to treatment – PGA, %age healing VAS ♦ Side effects – Clinical and Lab

Response to Treatment (Complete healing) Day No. of patients (%) 3: 09 (41%) 5: 17 (77%) 7 : 20 (91%)

Percentage healing of ulcer Day % of healing 3:77.95 ± :90.00 ± :95.00 ± 7.07 Mean healing time ± 2.16 ( days) Median healing time - 5 days

Improvement in VAS Day No. of patients (%) 3 09 (40.91) 5 21 (95.45) 7 22 (100)

Percentage improvement in VAS Day Mean VAS Imp 3:80.45 ± :97.69 ± :100 ± 0.00

Goldberg et al (JAAD 1986): n =157 ♦ Acyclovir 800 mg twice a day x 5 days ♦ Healing time : 5.2 days ♦ Acyclovir 200 mg five times a day x 5 days ♦ Healing time : 6.2 days Both regimens equally effective

Wald et al (2002): n = 84 ♦ Acyclovir 800 mg three times x 2 days ♦ Healing time: 4 days Shelley et al (Cutis 1996): n = 36 ♦ Acyclovir 800 mg “stat” at first signs/symptoms ♦ Prevented lesions in 81% (26/32) persons

Nilsen et al (Lancet 1982): ♦ Acyclovir 200 mg five times daily x 5 days ♦ Healing time : 5 days Our Study: ♦ Mean healing time ± 2.16 (3-10 days) ♦ Median healing time - 5 days

Conclusions ♦ Oral acyclovir in a dose of 1 gm BD x 3 days seems to be effective in the treatment of recurrent genital herpes ♦ Mean healing time : 4.9 days ♦ Median healing time - 5 days ♦ No significant side effects Oral acyclovir in high dose short course (1gm BD x 3d) regimen is effective and safe

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