Clinical trial NCT00164424: Episodic Acyclovir Therapy for Genital Ulcers
Official title: Impact of Episodic Acyclovir Therapy on Ulcer Duration and HIV Shedding From Genital Ulcers Among Men in South Africa
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: HIV Infections
Ulcer
Herpes Simplex
Keywords: HSV2
genital ulcer
HIV
South Africa
Treatment
Acyclovir
Prevention
Lead sponsor: Centers for Disease Control and Prevention
Sponsor class: FED
Collaborators: name: London School of Hygiene and Tropical Medicine
name: National Institute for Communicable Diseases, South Africa
First posted: 2005-09-14
Enrollment: 613
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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 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

Primary outcomes:
measure: Ulcer healing
Secondary outcomes:
measure: HIV viral load from genital ulcers
measure: HIV viral load in semen
Other outcomes:
Locations:
city: Johannesburg
country: South Africa
facility: Eloff Street Clinic
state: Gauteng
city: Johannesburg
country: South Africa
facility: Green Door, Alexandra Health Centre
state: Gauteng
Study officials:
affiliation: Centers for Disease Control and Prevention
name: Gabriela Paz Bailey, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: STIRC, National Institute for Communicable Diseases (NICD), South Africa
name: David Lewis, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Paz Bailey G, Sternberg M, Lewis DA, Puren A. Acute HIV infections among men with genital ulcer disease in South Africa. J Infect Dis. 2010 Jun 15;201(12):1811-5. doi: 10.1086/652785.
citation: Paz-Bailey G, Sternberg M, Puren AJ, Markowitz LE, Ballard R, Delany S, Hawkes S, Nwanyanwu O, Ryan C, Lewis DA. Improvement in healing and reduction in HIV shedding with episodic acyclovir therapy as part of syndromic management among men: a randomized, controlled trial. J Infect Dis. 2009 Oct 1;200(7):1039-49. doi: 10.1086/605647.