Anti-Herpetic Treatment of Genital Ulcer : Effect on HIV & Herpes Shedding (ANRS 1212)

This study has been completed.
Sponsor:
Information provided by:
French National Agency for Research on AIDS and Viral Hepatitis
ClinicalTrials.gov Identifier:
NCT00158483
First received: September 8, 2005
Last updated: December 29, 2008
Last verified: December 2008
  Purpose

Herpes virus type 2 (HSV-2) infection - as a cofactor of human immunodeficiency virus (HIV) transmission - can be targeted by anti-herpetic specific drugs, either as a continuous prophylactic treatment during its asymptomatic shedding phase, or as an episodic treatment during clinically-apparent genital ulcerations. The main objective of this trial will be to demonstrate that acyclovir treatment given during clinical episodes (primary infection or recurrences) can reduce genital shedding of HIV, thereby contributing to a reduction of HIV infectiousness of dually infected individuals (HIV+/HSV+).


Condition Intervention Phase
Ulcer
Herpes Genitalis
Drug: Acyclovir (ACV)
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: Prevention
Official Title: Anti-Herpetic Treatment Associated With Syndromic Management of Genital Ulcer in Africa: Clinical and Biological Evaluation on HIV-1 and HSV-2 Shedding (ANRS 1212)

Resource links provided by NLM:


Further study details as provided by French National Agency for Research on AIDS and Viral Hepatitis:

Primary Outcome Measures:
  • Difference of HIV-1 RNA and DNA shedding assessed by performing cervicovaginal lavage (CVL) HIV viral load, among groups
  • Difference of HSV-2 DNA shedding among groups

Enrollment: 449
Study Start Date: May 2003
Study Completion Date: October 2005
Detailed Description:

Objectives. The proposed project is a randomised placebo-controlled, double-blinded, multicentric therapeutic trial evaluating the association of antiherpetic treatment to the syndromic treatment for the management genital ulcers in Africa, and its impact on the genital shedding of HIV and of Herpes simplex hominis type 2 (HSV-2) virus.

Background. Recent epidemiological studies have shown that infection with HSV-2 is highly prevalent in sub-Saharan Africa, and that HSV-2 seropositivity is a marker of high-risk sexual behaviour. HSV-2 infection is increasingly being recognised as one of the commonest causes of genital ulceration in many African countries. HSV-2 infection may act as a major cofactor for HIV transmission, a fact that has long been underestimated. First, genital ulcers (caused by HSV-2) are by themselves cofactors of HIV transmission, either by increasing infectiousness of dually infected individuals (HSV+/HIV+), or by increasing susceptibility of the seronegative partner. Second, HSV-2 infection may transactivate in vivo the genital replication of HIV, thereby increasing the infectiousness of dually infected individuals.

Rationale and main objective. HSV-2 infection - as a cofactor of HIV transmission - can be targeted by anti-herpetic specific drugs, either as a continuous prophylactic treatment during its asymptomatic shedding phase, or as an episodic treatment during clinically-apparent genital ulcerations. The main objective of this trial will be to demonstrate that acyclovir treatment given during clinical episodes (primary infection or recurrences) can reduce genital shedding of free- or cell-associated HIV, thereby contributing to a reduction of HIV infectiousness of dually infected individuals (HIV+/HSV+). Given the present state of knowledge and hypotheses formulated around the possible role of HSV on the HIV epidemic in Africa, the proposed research will contribute to confirm or invalidate the existence of mutual reinforcement of HSV and HIV replication. This will represent a study of biological plausibility for such an in vivo interaction. In addition the chosen intervention strategy has practical and operational implications in that it will allow the evaluation of a novel approach to syndromic management of genital ulcers in Africa that could later lead to revisions of management guidelines.

Methods. Approximately 600 women presenting with genital ulcers will be enrolled over two years and in two sites: Bangui (Central African Republic) and Accra (Ghana). The syndromic management of patients will include antibiotics to cover the presumptive bacterial causes of genital ulcerations in these settings (chancroid and syphilis), according to national and international guidelines (CDC, UK national guidelines, WHO). In addition, women will be randomised to receive either antiherpetic treatment (acyclovir 400 mg 3 times daily for 5 days, according to UK national guidelines - a shorter regimen than US guidelines) or placebo (similar frequency and duration). Clinical examination and cervicovaginal samplings will be carried out at D0 and at each follow up visit at D2, D4, D7, D14 & D28. These samples will be tested for: etiological diagnosis of ulcers by multiplex PCR; measurement of HIV genital viral loads (measuring free RNA and cell-associated proviral DNA) and HSV-2 DNA genital load; and diagnosis of other common STDs (at D0). Blood samples will be collected at D0, D2 and D28 for HIV, syphilis and HSV-2 serological assays, and for HIV plasma loads as well as CD4 measurements.

The main outcome will be the determination of the impact of anti-herpetic treatment on HIV genital load (and as a corollary, on HSV2 genital load). It will also be possible to measure the impact of antibiotic treatment on HIV viral load. The study will allow to evaluate the validity of novel syndromic treatment approaches for genital ulcer disease, and a long term outcome may be the necessary revision of syndromic management guidelines for GUD to potentially include anti-herpetic treatment.

  Eligibility

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

Inclusion Criteria:

  • Clinically confirmed ulcer
  • Resident of city or planning to stay for 1 month
  • Be a women

Exclusion Criteria:

  • Pregnant women
  • Menstruating women
  • Positive protein urine test
  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: NCT00158483

Locations
Central African Republic
Centre MST/SIDA
Bangui, Central African Republic
Ghana
WAPTCAS
Accra, Ghana
Kumasi Hospital, Service d'infectiologie
Kumasi, Ghana
Sponsors and Collaborators
French National Agency for Research on AIDS and Viral Hepatitis
Investigators
Study Chair: Laurent Belec HEGP, Paris
Principal Investigator: Gérard Grésenguet Faculté de Médecine Université de Bangui
Study Chair: Philippe Mayaud London School of Hygiene and Tropical Medecine
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
ClinicalTrials.gov Identifier: NCT00158483     History of Changes
Other Study ID Numbers: ANRS 1212
Study First Received: September 8, 2005
Last Updated: December 29, 2008
Health Authority: Ghana: Ministry of Health

Keywords provided by French National Agency for Research on AIDS and Viral Hepatitis:
Genital herpes
Cofactors of sexual transmission
Syndromic treatment
Genital viral load
Ulcer

Additional relevant MeSH terms:
Herpes Genitalis
Ulcer
Herpes Simplex
Herpesviridae Infections
DNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Genital Diseases, Male
Genital Diseases, Female
Pathologic Processes
Acyclovir
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 11, 2014