Acyclovir Therapy for Genital Herpes Ulcers in HIV Negative African Women

Study Overview
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Brief Summary
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This is a prospective study to evaluate the pharmacokinetics, clinical and virologic response to acyclovir episodic therapy for genital herpes ulcers in HIV negative African women.

Detailed Description
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This is a two-part study designed to measure the Area Under the Curve (AUC) from a single dose of acyclovir 400mg in 60 African HIV-negative heterosexual women who have a history of genital ulcer disease (GUD), are HSV-2 seropositive and HIV-1 seronegative. The study will also examine the time to healing of genital lesion and duration of HSV shedding from GUD among 90 HIV negative African women who have a history of GUD and are Herpes Simplex Virus (HSV)-2 seropositive and HIV-1 seronegative randomized in a 2:1 ratio to receive episodic acyclovir or matching placebo.

Official Title
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Prospective Study of Pharmacokinetics, Clinical and Virologic Response to Acyclovir Episodic Therapy for Genital Herpes Ulcers in HIV Negative African Women

Conditions
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Ulcers of Female Genital Organs

Intervention / Treatment
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* Drug: Acyclovir
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: HIV negative as determined by concordant rapid testing HSV-2 seropositive (Focus HerpeSelect EIA >3.4) At least one prior occurrence of GUD 18 to 50 years of age Exclusion Criteria: Current use, or use within the past 7 days, of acyclovir, valacyclovir, or famciclovir Prior hypersensitivity and/or allergic reaction to acyclovir Use of probenecid, which prolongs renal excretion of acyclovir Current use, or use within the past 28 days, of an investigational agent Currently pregnant or nursing Currently plan to become pregnant during the next 3 months Currently consume, on average, more than 7 drinks of alcohol per week (for Part I) Current use of more than 20 cigarettes daily (for Part I) Any condition that in the opinion of the investigator will interfere with successful completion of all study procedures.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1 PK<br>400mg dose of acyclovir taken orally, followed by 2 ml blood plasma collection at 1,2,4,6 and 8 hours. | Drug: Acyclovir<br>* Single dose of acyclovir 200mg was given for pk study<br>|
| Active Comparator: Acyclovir<br>400 mg Acyclovir three times daily for 5 days | Drug: Acyclovir<br>* Single dose of acyclovir 200mg was given for pk study<br>|
| Placebo Comparator: Placebo<br>Placebo three times daily for 5 days | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the Curve (AUC) | Blood will be drawn for pharmacokinetic measures to determine whether there is a difference in African women vs. the existing AUC data for women and men in North America and Europe. | 0, 2, 3, 4, 6 and 8 hours post acyclovir administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to re-epithelization and time to cessation of HSV shedding | Daily assessment of response of genital lesions over 13 days by time to healing and duration of HSV shedding during acyclovir 400mg orally three times daily versus placebo three times daily for 5 days. | days 1-5, 7, 9, 11 and 13 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pharmacokinetics, Herpes simplex virus, Genital herpes ulcers