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

NCT01026454 | Completed Phase 4 Results

• 1 other identifier: 37162-A
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

HSV Infection; HIV Infection

Keywords

HSV; HIV

Outcome Measures

Primary Outcomes (1)

• Mean Level of HIV-1 RNA in Plasma of Participants While on Acyclovir or Valacyclovir.

  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.

  Weekly for 12 weeks per intervention

Secondary Outcomes (1)

• Safety of Valacyclovir 1.5 Gram Orally Twice Daily in HIV-1 Seropositive Persons.

  28 weeks

Study Arms (2)

acyclovir

ACTIVE COMPARATOR

acyclovir 400 mg orally twice daily

Drug: acyclovir

valacyclovir

ACTIVE COMPARATOR

valacyclovir 1.5 g orally twice daily

Drug: valacyclovir

Interventions

acyclovir DRUG

acyclovir 400 mg orally, twice daily for 12 weeks

acyclovir

valacyclovir DRUG

valacyclovir 1.5 g orally, twice daily, for 12 weeks

valacyclovir

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Washington: lead

Study Sites (1)

Thika Partners in Prevention

Thika, Kenya

Location

Related Publications (4)

• Brown EL, Wald A, Hughes JP, Morrow RA, Krantz E, Mayer K, Buchbinder S, Koblin B, Celum C. High risk of human immunodeficiency virus in men who have sex with men with herpes simplex virus type 2 in the EXPLORE study. Am J Epidemiol. 2006 Oct 15;164(8):733-41. doi: 10.1093/aje/kwj270. Epub 2006 Aug 8.

  PMID: 16896053 BACKGROUND

• Freeman EE, Weiss HA, Glynn JR, Cross PL, Whitworth JA, Hayes RJ. Herpes simplex virus 2 infection increases HIV acquisition in men and women: systematic review and meta-analysis of longitudinal studies. AIDS. 2006 Jan 2;20(1):73-83. doi: 10.1097/01.aids.0000198081.09337.a7.

  PMID: 16327322 BACKGROUND

• Schacker T, Zeh J, Hu H, Shaughnessy M, Corey L. Changes in plasma human immunodeficiency virus type 1 RNA associated with herpes simplex virus reactivation and suppression. J Infect Dis. 2002 Dec 15;186(12):1718-25. doi: 10.1086/345771. Epub 2002 Nov 22.

  PMID: 12447756 BACKGROUND

• Mugwanya K, Baeten JM, Mugo NR, Irungu E, Ngure K, Celum C. High-dose valacyclovir HSV-2 suppression results in greater reduction in plasma HIV-1 levels compared with standard dose acyclovir among HIV-1/HSV-2 coinfected persons: a randomized, crossover trial. J Infect Dis. 2011 Dec 15;204(12):1912-7. doi: 10.1093/infdis/jir649. Epub 2011 Oct 12.

  PMID: 21998479 DERIVED

MeSH Terms

Conditions

Herpes Simplex; HIV Infections

Interventions

Acyclovir; Valacyclovir

Condition Hierarchy (Ancestors)

Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Skin Diseases, Viral; Skin Diseases, Infectious; Skin Diseases; Skin and Connective Tissue Diseases; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Connie Celum, MD, MPH
• Organization: University of Washington

ccelum@uw.edu

206-520-3800

Study Officials

• Connie Celum, MD, MPH

  University of Washington

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: US Principal Investigator

Study Record Dates

• First Submitted: December 2, 2009
• First Posted: December 4, 2009
• Study Start: February 1, 2010
• Primary Completion: November 1, 2010
• Study Completion: December 1, 2010
• Last Updated: April 8, 2014
• Results First Posted: March 5, 2014

Record last verified: 2014-03

Locations

KE (1)