Clinical Trials For Genital Herpes Valacyclovir Versus Acyclovir as HSV-2 Suppressive Therapy: Effect on Plasma HIV-1 Levels Among HIV-1/HSV-2 Co-infected Persons (ACV-VAL)

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

This study is currently recruiting participants.

Verified by University of Washington, March 2010

First Received: December 2, 2009   Last Updated: March 12, 2010   History of Changes

Sponsor:

University of Washington

Information provided by:

University of Washington

ClinicalTrials.gov Identifier:

NCT01026454

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 IV


Study Type:

Interventional

Study Design:

Allocation: Randomized

Control: Active Control

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:


MedlinePlus related topics: AIDS Herpes Simplex

Drug Information available for: Acyclovir Acyclovir sodium Valaciclovir Valacyclovir hydrochloride

U.S. FDA Resources


Further study details as provided by University of Washington:


Primary Outcome Measures:

Presence and quantity of the 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: 28 weeks ] [ Designated as safety issue: No ]


Secondary Outcome Measures:

Evaluate the safety of valacyclovir 1.5 gram orally twice daily in HIV-1 seropositive persons. [ Time Frame: 28 weeks ] [ Designated as safety issue: Yes ]


Estimated Enrollment:

32

Study Start Date:

February 2010

Estimated Study Completion Date:

February 2011

Estimated Primary Completion Date:

December 2010 (Final data collection date for primary outcome measure)

Arms

Assigned Interventions

Acyclovir: Active Comparator

Acyclovir 400 mg orally twice daily

Drug: acyclovir

Acyclovir 400 mg orally, twice daily for 12 weeks

Valacyclovir: Active Comparator

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

Please refer to this study by its ClinicalTrials.gov identifier: NCT01026454


Contacts

Contact: Nelly Mugo, MBChB, M.Med, MPH

254 2 736 744

rwamba@u.washington.edu

Contact: Elizabeth Irungu, NBChB

254 0 67 22561

eirungu@pipsthika.org


Locations

Kenya

Thika Partners in Prevention

Recruiting

Thika, Kenya

Contact: Nelly Mugo, MBChB, M.Med, MPH     254 2 736 744     rwamba@u.washington.edu

Contact: Elizabeth Irungu, NBChB     254 0 672 2561     eirungu@pipsthika.org

Principal Investigator: Nelly Mugo, MBChB, M.Med, MPH

Sponsors and Collaborators

University of Washington

Investigators

Principal Investigator:

Connie Celum, MD, MPH

University of Washington

More Information


Publications:

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.

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.

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.


Responsible Party:

University of Washington ( Connie Celum, MD, MPH )

ClinicalTrials.gov Identifier:

NCT01026454 History of Changes

Other Study ID Numbers:

37162-A

Study First Received:

December 2, 2009

Last Updated:

March 12, 2010

Health Authority:

United States: Institutional Review Board


Keywords provided by University of Washington:

HSV

HIV


Additional relevant MeSH terms:

Herpes Simplex

Anti-Infective Agents

RNA Virus Infections

Sexually Transmitted Diseases, Viral

Slow Virus Diseases

Skin Diseases

Immune System Diseases

Acquired Immunodeficiency Syndrome

Antiviral Agents

Pharmacologic Actions

Immunologic Deficiency Syndromes

Herpesviridae Infections

Valacyclovir

Skin Diseases, Viral

Virus Diseases

Skin Diseases, Infectious

Acyclovir

HIV Infections

Therapeutic Uses

Sexually Transmitted Diseases

Lentivirus Infections

DNA Virus Infections

Retroviridae Infections


ClinicalTrials.gov processed this record on June 15, 2010

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

This study is currently recruiting participants.

Verified by University of Washington, March 2010

First Received: December 2, 2009   Last Updated: March 12, 2010   History of Changes

Sponsor:

University of Washington

Information provided by:

University of Washington

ClinicalTrials.gov Identifier:

NCT01026454

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 IV


Study Type:

Interventional

Study Design:

Allocation: Randomized

Control: Active Control

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:


MedlinePlus related topics: AIDS Herpes Simplex

Drug Information available for: Acyclovir Acyclovir sodium Valaciclovir Valacyclovir hydrochloride

U.S. FDA Resources


Further study details as provided by University of Washington:


Primary Outcome Measures:

Presence and quantity of the 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: 28 weeks ] [ Designated as safety issue: No ]


Secondary Outcome Measures:

Evaluate the safety of valacyclovir 1.5 gram orally twice daily in HIV-1 seropositive persons. [ Time Frame: 28 weeks ] [ Designated as safety issue: Yes ]


Estimated Enrollment:

32

Study Start Date:

February 2010

Estimated Study Completion Date:

February 2011

Estimated Primary Completion Date:

December 2010 (Final data collection date for primary outcome measure)

Arms

Assigned Interventions

Acyclovir: Active Comparator

Acyclovir 400 mg orally twice daily

Drug: acyclovir

Acyclovir 400 mg orally, twice daily for 12 weeks

Valacyclovir: Active Comparator

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

Please refer to this study by its ClinicalTrials.gov identifier: NCT01026454


Contacts

Contact: Nelly Mugo, MBChB, M.Med, MPH

254 2 736 744

rwamba@u.washington.edu

Contact: Elizabeth Irungu, NBChB

254 0 67 22561

eirungu@pipsthika.org


Locations

Kenya

Thika Partners in Prevention

Recruiting

Thika, Kenya

Contact: Nelly Mugo, MBChB, M.Med, MPH     254 2 736 744     rwamba@u.washington.edu

Contact: Elizabeth Irungu, NBChB     254 0 672 2561     eirungu@pipsthika.org

Principal Investigator: Nelly Mugo, MBChB, M.Med, MPH

Sponsors and Collaborators

University of Washington

Investigators

Principal Investigator:

Connie Celum, MD, MPH

University of Washington

More Information


Publications:

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.

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.

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.


Responsible Party:

University of Washington ( Connie Celum, MD, MPH )

ClinicalTrials.gov Identifier:

NCT01026454 History of Changes

Other Study ID Numbers:

37162-A

Study First Received:

December 2, 2009

Last Updated:

March 12, 2010

Health Authority:

United States: Institutional Review Board


Keywords provided by University of Washington:

HSV

HIV


Additional relevant MeSH terms:

Herpes Simplex

Anti-Infective Agents

RNA Virus Infections

Sexually Transmitted Diseases, Viral

Slow Virus Diseases

Skin Diseases

Immune System Diseases

Acquired Immunodeficiency Syndrome

Antiviral Agents

Pharmacologic Actions

Immunologic Deficiency Syndromes

Herpesviridae Infections

Valacyclovir

Skin Diseases, Viral

Virus Diseases

Skin Diseases, Infectious

Acyclovir

HIV Infections

Therapeutic Uses

Sexually Transmitted Diseases

Lentivirus Infections

DNA Virus Infections

Retroviridae Infections


ClinicalTrials.gov processed this record on June 15, 2010