HSV-2 Suppression to Reduce HIV-1 Levels in HIV-1, HSV-2 co-Infected Men. - Full Text View

Sponsor:	University of Washington
Collaborators:	GlaxoSmithKline Asociación Civil Impacta Salud y Educación, Peru
Information provided by:	University of Washington
ClinicalTrials.gov Identifier:	NCT00378976

Purpose

Over 80% of HIV-1 infected persons are also seropositive for HSV-2. Increasingly, clinical and epidemiologic evidence show the role of HSV in increasing HIV infectiousness. The evidence suggests that that HSV is an important cofactor in HIV transmission.

The trial's purpose is to assess the reduction in HIV shedding associated with valacyclovir for suppression of HSV-2 reactivation.

This proof-of-concept, randomized, double-blind, placebo controlled crossover trial of 20 HIV/HSV-2 co-infected men, assessed the effects of daily valacyclovir on HIV-1 levels in the plasma and rectal mucosa secretions.

Condition	Intervention	Phase
HIV Infection Herpes Simplex Sexually Transmitted Diseases	Drug: valacyclovir Drug: matching placebo	Phase III

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Crossover Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Prevention
Official Title:	A Randomized, Double-Blind, Placebo-Controlled Crossover Trial of Valacyclovir for Suppression of HSV and HIV Shedding in HIV-1, HSV-2 Coinfected Men Who Have Sex With Men (MSM).

Resource links provided by NLM:

Genetics Home Reference related topics: complement factor I deficiency

MedlinePlus related topics: HIV/AIDS Herpes Simplex Sexually Transmitted Diseases

Drug Information available for: Valaciclovir Valacyclovir hydrochloride

U.S. FDA Resources

Further study details as provided by University of Washington:

Primary Outcome Measures:

Reduction in anogenital HIV-1 shedding with suppression of HSV-2 reactivation. [ Time Frame: 18 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Evaluate HSV-2 suppression with decreased plasma HIV RNA levels [ Time Frame: 18 weeks ] [ Designated as safety issue: No ]
Assess the effect of daily valacyclovir on pharyngeal shedding in HSV-1 seropositive individuals [ Time Frame: 18 weeks ] [ Designated as safety issue: No ]
Determine the temporal pattern of HIV shedding in the rectum, pharynx and semen with respect to mucosal HSV-1 and HSV-2 reactivation; Determine HSV-2 suppression and HIV replication within rectal mucosa. [ Time Frame: 18 weeks ] [ Designated as safety issue: No ]

Enrollment:	20
Study Start Date:	August 2003
Study Completion Date:	July 2004

Arms	Assigned Interventions
Experimental: 1	Drug: valacyclovir 500 mg twice-daily oral
Placebo Comparator: 2	Drug: matching placebo twice daily as per experimental drug

Detailed Description:

Herpes simplex virus type 2 (HSV-2) is common among HIV infected persons. HSV-2 reactivation is associated with increased plasma and genital HIV-1 levels, and in vitro, HSV-2 upregulates HIV transcription.

The trial assessed whether HSV-2 suppression reduces rectal and plasma HIV-1 levels in HIV-1, HSV-2 co-infected men who have sex with men (MSM).

Conducted in Lima Peru, 20 antiretroviral naive HIV-1 and HSV-2 seropositive MSM with CD4 >200 were randomly assigned to receive valacyclovir 500 mg bid or placebo for 8 weeks, than a 2 week washout period, followed by the alternative regimen for 8 weeks. Men collected daily home anogenital swabs for HSV DNA PCR, had three weekly anoscopy procedures for collection of rectal mucosal secretions for HIV-1 RNA, HSV DNA, and weekly plasma HIV-1 RNA by PCR. Outcomes were plasma and rectal HIV-1 levels by study arm.

Eligibility

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

Criteria

Inclusion Criteria:

Greater than 18 years old,
Documented HIV-1 seropositive,
CD4 count greater than 200,
Not on HIV antiretroviral therapy,
HSV-2 seropositive as determined by Focus EIA (IN >3.5)
Not intending to move out of the area for the duration of study participation.
Willing and able to:provide independent written informed consent;undergo clinical evaluations;take study drug as directed;adhere to follow-up schedule.
Bacterial STDs (symptomatic STD syndromes or laboratory-confirmed asymptomatic gonorrhea and syphilis) are treated within two weeks of study enrollment and random assignment.

Exclusion Criteria:

MSM who meet any of the following criteria are not eligible for this study:

Known history of adverse reaction to valacyclovir, acyclovir or famciclovir;
Planned open label use of acyclovir, valacyclovir, or famciclovir
Known medical history of seizures
Known renal failure, serum creatinine >2.0mg/dl
Hematocrit < 30 %

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00378976

Locations

Peru
Asociacion Civil Impacta Salud y Educacion
Lima, Peru

Sponsors and Collaborators

University of Washington

GlaxoSmithKline

Asociación Civil Impacta Salud y Educación, Peru

Investigators

Principal Investigator:

Connie Celum, MD, MPH

University of Washington

More Information

No publications provided by University of Washington

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Zuckerman RA, Lucchetti A, Whittington WL, Sánchez J, Coombs RW, Magaret A, Wald A, Corey L, Celum C. HSV suppression reduces seminal HIV-1 levels in HIV-1/HSV-2 co-infected men who have sex with men. AIDS. 2009 Feb 20;23(4):479-83.

Zuckerman RA, Lucchetti A, Whittington WL, Sanchez J, Coombs RW, Zuñiga R, Magaret AS, Wald A, Corey L, Celum C. Herpes simplex virus (HSV) suppression with valacyclovir reduces rectal and blood plasma HIV-1 levels in HIV-1/HSV-2-seropositive men: a randomized, double-blind, placebo-controlled crossover trial. J Infect Dis. 2007 Nov 15;196(10):1500-8. Epub 2007 Oct 31.

Responsible Party:	Connie Celum, MD, MPH, University of Washington
ClinicalTrials.gov Identifier:	NCT00378976 History of Changes
Other Study ID Numbers:	02-3200-A-05, AI277S7;AI38858;AI30731
Study First Received:	September 19, 2006
Last Updated:	December 11, 2007
Health Authority:	United States: Institutional Review Board

Keywords provided by University of Washington:

HIV infection
HIV shedding
HSV suppression
Co-infected

MSM
Reactivation
Valacyclovir

Additional relevant MeSH terms:

HIV Infections
Acquired Immunodeficiency Syndrome
Herpes Simplex
Sexually Transmitted Diseases
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Herpesviridae Infections

DNA Virus Infections
Skin Diseases, Viral
Skin Diseases, Infectious
Skin Diseases
Infection
Genital Diseases, Male
Genital Diseases, Female
Valacyclovir
Acyclovir
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on February 09, 2012