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

HIV Infection Clinical Trial

— ACV-VAL  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01026454
• Other study ID #: 37162-A
• Status: Completed
• Phase: Phase 4
• First received: December 2, 2009
• Last updated: March 10, 2014
• Start date: February 2010
• Est. completion date: December 2010

Study information

• Verified date: March 2014
• Source: University of Washington
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 32
• Est. completion date: December 2010
• Est. primary completion date: November 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• HIV Infection
• HSV Infection
• Infection

Intervention

Drug:
• acyclovir
acyclovir 400 mg orally, twice daily for 12 weeks
• valacyclovir
valacyclovir 1.5 g orally, twice daily, for 12 weeks

Locations

Country	Name	City	State
Kenya	Thika Partners in Prevention	Thika

Sponsors (1)

Lead Sponsor	Collaborator
University of Washington

Country where clinical trial is conducted

Kenya, 

References & Publications (3)

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. Epub 2006 Aug 8. — View Citation

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. Review. — View Citation

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. Epub 2002 Nov 22. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	Safety of Valacyclovir 1.5 Gram Orally Twice Daily in HIV-1 Seropositive Persons.		28 weeks	Yes