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

Primary Purpose

HSV Infection, HIV Infection

Status

Completed

Phase

Phase 4

Locations

Kenya

Study Type

Interventional

Intervention

acyclovir

valacyclovir

About this trial

This is an interventional treatment trial for HSV Infection focused on measuring HSV, HIV

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Thika Partners in Prevention

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Arm Label

acyclovir

valacyclovir

Arm Description

acyclovir 400 mg orally twice daily

valacyclovir 1.5 g orally twice daily

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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

Full Information

NCT ID

NCT01026454

First Posted

December 2, 2009

Last Updated

March 10, 2014

Sponsor

University of Washington

1. Study Identification

Unique Protocol Identification Number

NCT01026454

Brief Title

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

Acronym

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

Study Type

Interventional

2. Study Status

Record Verification Date

March 2014

Overall Recruitment Status

Completed

Study Start Date

February 2010 (undefined)

Primary Completion Date

November 2010 (Actual)

Study Completion Date

December 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

University of Washington

4. Oversight

Data Monitoring Committee

5. Study Description

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

HSV Infection, HIV Infection

Keywords

HSV, HIV

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Crossover Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

32 (Actual)

8. Arms, Groups, and Interventions

Arm Title

acyclovir

Arm Type

Active Comparator

Arm Description

acyclovir 400 mg orally twice daily

Arm Title

valacyclovir

Arm Type

Active Comparator

Arm Description

valacyclovir 1.5 g orally twice daily

Intervention Type

Drug

Intervention Name(s)

acyclovir

Intervention Description

acyclovir 400 mg orally, twice daily for 12 weeks

Intervention Type

Drug

Intervention Name(s)

valacyclovir

Intervention Description

valacyclovir 1.5 g orally, twice daily, for 12 weeks

Primary Outcome Measure Information:

Title

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

Description

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.

Time Frame

Weekly for 12 weeks per intervention

Secondary Outcome Measure Information:

Title

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

Time Frame

28 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Connie Celum, MD, MPH

Organizational Affiliation

University of Washington

Official's Role

Principal Investigator

Facility Information:

Facility Name

Thika Partners in Prevention

City

Thika

Country

Kenya

12. IPD Sharing Statement

Citations:

PubMed Identifier

16896053

Citation

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.

Results Reference

background

PubMed Identifier

16327322

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. doi: 10.1097/01.aids.0000198081.09337.a7.

Results Reference

background

PubMed Identifier

12447756

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. doi: 10.1086/345771. Epub 2002 Nov 22.

Results Reference

background

PubMed Identifier

21998479

Citation

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.

Results Reference

derived

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

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