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Episodic Acyclovir Therapy for Genital Ulcers

This study has been completed.
Sponsor:
Collaborators:
London School of Hygiene and Tropical Medicine
STI Reference Center, National Institute for Communicable Diseases, Johannesburg, South Africa
Information provided by (Responsible Party):
Centers for Disease Control and Prevention
ClinicalTrials.gov Identifier:
NCT00164424
First received: September 9, 2005
Last updated: September 10, 2012
Last verified: September 2012
  Purpose

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.


Condition Intervention Phase
HIV Infections
Ulcer
Herpes Simplex
Drug: Acyclovir
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: Impact of Episodic Acyclovir Therapy on Ulcer Duration and HIV Shedding From Genital Ulcers Among Men in South Africa

Resource links provided by NLM:


Further study details as provided by Centers for Disease Control and Prevention:

Primary Outcome Measures:
  • Ulcer healing

Secondary Outcome Measures:
  • HIV viral load from genital ulcers
  • HIV viral load in semen

Enrollment: 613
Study Start Date: March 2005
Study Completion Date: July 2011
Primary Completion Date: March 2009 (Final data collection date for primary outcome measure)
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00164424

Locations
South Africa
Eloff Street Clinic
Johannesburg, Gauteng, South Africa
Green Door, Alexandra Health Centre
Johannesburg, Gauteng, South Africa
Sponsors and Collaborators
London School of Hygiene and Tropical Medicine
STI Reference Center, National Institute for Communicable Diseases, Johannesburg, 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
  More Information

No publications provided by Centers for Disease Control and Prevention

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Centers for Disease Control and Prevention
ClinicalTrials.gov Identifier: NCT00164424     History of Changes
Other Study ID Numbers: CDC-NCHSTP-4294
Study First Received: September 9, 2005
Last Updated: September 10, 2012
Health Authority: United States: Federal Government

Keywords provided by Centers for Disease Control and Prevention:
HSV2
genital ulcer
HIV
South Africa
Treatment
Acyclovir
Prevention

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
HIV Infections
Herpes Simplex
Ulcer
DNA Virus Infections
Herpesviridae Infections
Immune System Diseases
Immunologic Deficiency Syndromes
Lentivirus Infections
Pathologic Processes
RNA Virus Infections
Retroviridae Infections
Sexually Transmitted Diseases
Sexually Transmitted Diseases, Viral
Skin Diseases
Skin Diseases, Infectious
Skin Diseases, Viral
Slow Virus Diseases
Virus Diseases
Acyclovir
Anti-Infective Agents
Antiviral Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on November 20, 2014