HSV-2 Suppression to Reduce HIV-1 Levels in HIV-1, HSV-2 Co-infected Men.

Sponsor

University of Washington (Other)

Overall Status

Completed

CT.gov ID

NCT00378976

Collaborator

GlaxoSmithKline (Industry), Asociación Civil Impacta Salud y Educación, Peru (Other)

Enrollment

Location

Arms

Duration (Months)

1.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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 or Disease	Intervention/Treatment	Phase
HIV Infection Herpes Simplex Sexually Transmitted Diseases	Drug: valacyclovir Drug: matching placebo	Phase 3

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

20 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

Quadruple (Participant, Care Provider, 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).

Study Start Date :

Aug 1, 2003

Actual Study Completion Date :

Jul 1, 2004

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1	Drug: valacyclovir 500 mg twice-daily oral
Placebo Comparator: 2	Drug: matching placebo twice daily as per experimental drug

Arm

Intervention/Treatment

Experimental: 1

Drug: valacyclovir

500 mg twice-daily oral

Placebo Comparator: 2

Drug: matching placebo

twice daily as per experimental drug

Outcome Measures

Primary Outcome Measures

Reduction in anogenital HIV-1 shedding with suppression of HSV-2 reactivation. [18 weeks]

Secondary Outcome Measures

Evaluate HSV-2 suppression with decreased plasma HIV RNA levels [18 weeks]
Assess the effect of daily valacyclovir on pharyngeal shedding in HSV-1 seropositive individuals [18 weeks]
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. [18 weeks]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

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.