Episodic Acyclovir Therapy for Genital Ulcers

September 10, 2012 updated by: Centers for Disease Control and Prevention

Impact of Episodic Acyclovir Therapy on Ulcer Duration and HIV Shedding From Genital Ulcers Among Men in South Africa

The purpose of this study is to determine if acyclovir episodic treatment has an effect in ulcer healing and if it should be added to the syndromic management of genital ulcer disease.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Background and Objectives: Herpes simplex virus type 2 (HSV-2) is the primary cause of genital ulcer and one of the most prevalent sexually transmitted infections (STI) worldwide. HSV-2 has been recognized as a risk factor for HIV in multiple studies. A substantial shift in the aetiology of genital ulcer disease (GUD) towards genital herpes has been noted in many countries in Africa, especially those with mature HIV epidemics. Some countries guided by the predominance of HSV-2 as the aetiology of GUD in their country, are changing syndromic guidelines to include acyclovir as part of the treatment for GUD. Little data is available to support this decision in terms of its effect on clinical course and its cost-effectiveness. Yet, substantial investment would be needed in poor countries to add acyclovir to their essential drug list. Studies to determine the appropriateness of episodic acyclovir therapy for HSV-2 in the developing world are needed.

Episodic therapy with acyclovir both as a treatment modality and as an HIV-prevention strategy is appealing, in terms of cost and sustainability. However, it is not clear which will be its impact under field conditions in which there would be delay in symptom recognition and treatment initiation, and whether these conditions could be optimized through patient education. We propose to conduct a randomized placebo-controlled trial of the effect of HSV-2 episodic therapy on symptomatic herpes and on HIV shedding from genital ulcers. This study will help answer the question if acyclovir therapy for herpes should be added into the syndromic management of genital ulcer disease. Acyclovir has an acceptable profile for widespread STI treatment and is now relatively inexpensive and well-tolerated. Given that HSV-2 is the leading cause of GUD in the developing world, this approach could have great public health importance, by providing a safe, acceptable, and cost-effective method to treat genital ulcer disease and potentially reduce HIV transmission. If acyclovir therapy reduces HIV shedding, its incorporation into syndromic management would provide and effective way to scale it up as a public health intervention.

Methods: We plan an individually randomized double blind placebo-control trial of the WHO and US CDC recommended dose of 3-times daily acyclovir for a 5-day treatment course. The trial will be conducted at two primary health care clinics in Johannesburg, South Africa. A total of 600 men presenting to the clinic with GUD will be enrolled in the study. Consenting participants will be randomized to receive either acyclovir plus syndromic management or placebo plus syndromic management. Syndromic management for genital ulcer disease will consist of one dose antibiotics to cover for syphilis and chancroid. Participants will be followed for a month; during follow-up visits duration of ulcers, ulcer number and size will be evaluated and ulcer, blood and semen samples collected to test for HIV RNA viral loads among HIV-positives and for HSV-2 shedding.

Timeline: Duration of the project is 2 years

Expected Outcomes: The main outcome of the study will be the evaluation of the impact of acyclovir therapy on ulcer healing. We will also measure the impact of acyclovir therapy on HIV and HSV-2 viral load from genital ulcers and HIV viral load in semen.

Study Type

Interventional

Enrollment (Actual)

613

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • South Africa
    • Gauteng
      • Johannesburg, Gauteng, South Africa
        • Eloff Street Clinic
      • Johannesburg, Gauteng, South Africa
        • Green Door, Alexandra Health Centre

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Description

Inclusion Criteria:

  • Males presenting at the primary health care clinic with a genital ulcer
  • Age 18 years or older
  • Willing and able to give informed consent
  • Willing to be tested for HSV and HIV
  • Willing and able to comply with the study protocol including follow-up visits
  • Willing to accept therapy by chance

Exclusion Criteria:

  • Extensive ulceration
  • Ulceration >1 month
  • History of adverse reaction to acyclovir
  • Taking suppressive therapy for genital herpes
  • History of renal insufficiency or proteinuria

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Ulcer healing

Secondary Outcome Measures

Outcome Measure
HIV viral load from genital ulcers
HIV viral load in semen

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Centers for Disease Control and Prevention

Collaborators

London School of Hygiene and Tropical Medicine
National Institute for Communicable Diseases, South Africa

Investigators

  • Principal Investigator: Gabriela Paz Bailey, MD, Centers for Disease Control and Prevention
  • Principal Investigator: David Lewis, MD, STIRC, National Institute for Communicable Diseases (NICD), South Africa

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2005

Primary Completion (Actual)

March 1, 2009

Study Completion (Actual)

July 1, 2011

Study Registration Dates

First Submitted

September 9, 2005

First Submitted That Met QC Criteria

September 10, 2005

First Posted (Estimate)

September 14, 2005

Study Record Updates

Last Update Posted (Estimate)

September 11, 2012

Last Update Submitted That Met QC Criteria

September 10, 2012

Last Verified

September 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDC-NCHSTP-4294

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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