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

Condition(s) targeted: HIV Infection; Herpes Simplex; Sexually Transmitted Diseases

Intervention: valacyclovir (Drug); matching placebo (Drug)

Phase: Phase 3

Status: Completed

Sponsored by: University of Washington

Official(s) and/or principal investigator(s):
Connie Celum, MD, MPH, Principal Investigator, Affiliation: University of Washington

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.

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 design: Prevention, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Crossover Assignment, Efficacy Study

Primary outcome: Reduction in anogenital HIV-1 shedding with suppression of HSV-2 reactivation.

Secondary outcome:

Evaluate HSV-2 suppression with decreased plasma HIV RNA levels

Assess the effect of daily valacyclovir on pharyngeal shedding in HSV-1 seropositive individuals

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.

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.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Male.

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 %

Asociacion Civil Impacta Salud y Educacion, Lima, Peru

Starting date: August 2003
Ending date: July 2004
Last updated: December 11, 2007