Valacyclovir vs. Acyclovir as HSV-2 Suppressive Therapy: Effect on Plasma HIV-1 Levels Among HIV-1/HSV-2 Co-infected Persons (ACV-VAL)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Connie Celum, University of Washington
ClinicalTrials.gov Identifier:
NCT01026454
First received: December 2, 2009
Last updated: March 10, 2014
Last verified: March 2014
  Purpose

The purpose of this study is to determine whether treating HSV-2 with either valacyclovir or acyclovir is more effective in suppressing HIV-1 virus levels in people co-infected with HIV-1 and HSV-2.


Condition Intervention Phase
HSV Infection
HIV Infection
Drug: acyclovir
Drug: valacyclovir
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized, Open-label, Crossover Trial of the Effect of High-dose Daily HSV-2 Suppressive Therapy on Plasma HIV-1 Levels Among HIV-1/HSV-2 Co-infected Persons

Resource links provided by NLM:


Further study details as provided by University of Washington:

Primary Outcome Measures:
  • Mean Level of HIV-1 RNA in Plasma of Participants While on Acyclovir or Valacyclovir. [ Time Frame: Weekly for 12 weeks per intervention ] [ Designated as safety issue: No ]
    Mean level of HIV-1 RNA in plasma of participants while on 400 mg twice daily of acyclovir versus while on 1.5 g twice daily of valacyclovir.


Secondary Outcome Measures:
  • Safety of Valacyclovir 1.5 Gram Orally Twice Daily in HIV-1 Seropositive Persons. [ Time Frame: 28 weeks ] [ Designated as safety issue: Yes ]

Enrollment: 32
Study Start Date: February 2010
Study Completion Date: December 2010
Primary Completion Date: November 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: acyclovir
acyclovir 400 mg orally twice daily
Drug: acyclovir
acyclovir 400 mg orally, twice daily for 12 weeks
Active Comparator: valacyclovir
valacyclovir 1.5 g orally twice daily
Drug: valacyclovir
valacyclovir 1.5 g orally, twice daily, for 12 weeks

Detailed Description:

Sexual transmission is responsible for the vast majority of HIV-1 infections among adults worldwide. In sub-Saharan Africa, the region hardest hit by the HIV-1 epidemic, HSV-2 prevalences of 30-50% have been seen in the general population with prevalence up to 90% in infected with HIV-1. HSV-2 is common in those with, or at risk for, HIV-1 infection, and HSV-2 reactivation increases HIV-1 acquisition and infectiousness. Recent studies have shown that suppression of HSV-2 has a sustained effect on lowering HIV-1 levels in blood plasma. New data have raised the question whether higher doses of HSV-2 suppressive therapy might be more effective at suppressing HIV-1 levels. Acyclovir and valacyclovir, chosen for use in this study, are safe and effective treatments for decreasing the frequency of HSV-2 reactivation and shedding. The standard dose of acyclovir is 400 mg twice a day. Valacyclovir, a drug that converts to acyclovir after absorption, delivers higher concentrations of acyclovir. 1.5 grams of valacyclovir, will be used to provide a higher dose of acyclovir, and will be compared with the standard dose of 400 mg twice a day of acyclovir.

  Eligibility

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

Inclusion Criteria:

  • HIV-1 seropositive
  • Not on HIV-1 antiretroviral therapy nor planning to initiate antiretroviral therapy during the study period
  • CD4 cell count >250 cell/µL
  • Not otherwise eligible for antiretroviral therapy according to Uganda national guidelines
  • Detectable HIV-1 plasma viral load
  • HSV-2 seropositive
  • Not intending to move out of the area for the duration of study participation.
  • Able to participate in the study at the Partners in Prevention site in Thika, Kenya

Exclusion Criteria:

  • Known history of adverse reaction to acyclovir, valacyclovir, or famciclovir.
  • Planned use of acyclovir, valacyclovir, or famciclovir
  • Use of ganciclovir, foscarnet, or cidofovir
  • Known medical history of seizures
  • Serum creatinine >1.5 mg/dL
  • AST or ALT >3 times upper limit of normal
  • Hematocrit <30 %
  • Absolute neutrophil count <1000
  • Platelet count <75,000
  • History of thrombotic microangiopathy
  • Any other condition which, in the opinion of the principal investigator, may compromise the ability to follow study procedures and complete the study
  • Participation in another HIV therapeutics trial
  • For women, pregnancy as confirmed by a urine pregnancy 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: NCT01026454

Locations
Kenya
Thika Partners in Prevention
Thika, Kenya
Sponsors and Collaborators
University of Washington
Investigators
Principal Investigator: Connie Celum, MD, MPH University of Washington
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Connie Celum, US Principal Investigator, University of Washington
ClinicalTrials.gov Identifier: NCT01026454     History of Changes
Other Study ID Numbers: 37162-A
Study First Received: December 2, 2009
Results First Received: November 15, 2013
Last Updated: March 10, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by University of Washington:
HSV
HIV

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

ClinicalTrials.gov processed this record on October 21, 2014