HSV-2 Suppression to Reduce HIV-1 Levels in HIV-1 Co-Infected Persons

Condition(s) targeted: HIV Infections; 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 HSV is an important co-factor in HIV transmission.

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

This randomized, double-blind, placebo controlled crossover trial of 20 HIV/HSV-2 co-infected women assessed the effects of daily valacyclovir on HIV-1 levels in blood and body fluids.

Official title: A Randomized,Double-Blind , Placebo-Controlled Crossover Trial of Antivirals for Suppression of HSV and HIV Shedding in HIV-1, HSV-2 Co-Infected Persons

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

Primary outcome: Plasma HIV-1 levels and HIV-1 mucosal shedding

Secondary outcome:

Mucosal HSV-2 shedding

Determine the temporal pattern of HIV shedding with respect to HSV-1 and HSV-2 reactivation;

Detailed description: Conducted in Lima Peru, 20 HIV-1 and HSV-2 seropositive women with CD4 counts greater than 200 and on no antiretroviral therapy were randomly assigned to receive valacyclovir 500 mg bid or placebo for the first 8 weeks of the study. After these 8 weeks, a 2-week washout period followed, which was then followed by the alternative regimen for 8 weeks.

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

Criteria:

Inclusion Criteria:

- Greater than 18 years old woman,

- 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:

Women 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: January 2005
Ending date: December 2007
Last updated: March 18, 2008