Clinical trial NCT00465205: HSV-2 Suppression to Reduce HIV-1 Levels in HIV-1 Co-infected Persons
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: HIV Infections
Herpes Simplex
Sexually Transmitted Diseases
Keywords: HIV infection
HIV Shedding
HSV suppression
Co-infected
Women
Reactivation
Valacyclovir
Treatment Naive
Lead sponsor: University of Washington
Sponsor class: OTHER
Collaborators: name: GlaxoSmithKline
name: Asociación Civil Impacta Salud y Educación, Peru
First posted: 2007-04-24
Enrollment: 20
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: PREVENTION

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 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.

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.

Eligibility 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 %

Primary outcomes:
measure: Plasma HIV-1 levels and HIV-1 mucosal shedding
timeFrame: 18 weeks
Secondary outcomes:
measure: Mucosal HSV-2 shedding
timeFrame: 18 weeks
measure: Determine the temporal pattern of HIV shedding with respect to HSV-1 and HSV-2 reactivation;
timeFrame: 18 weeks
Other outcomes:
Locations:
city: Lima
country: Peru
facility: Asociacion Civil Impacta Salud y Educacion
Study officials:
affiliation: University of Washington
name: Connie Celum, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References:
citation: Baeten JM, Strick LB, Lucchetti A, Whittington WL, Sanchez J, Coombs RW, Magaret A, Wald A, Corey L, Celum C. Herpes simplex virus (HSV)-suppressive therapy decreases plasma and genital HIV-1 levels in HSV-2/HIV-1 coinfected women: a randomized, placebo-controlled, cross-over trial. J Infect Dis. 2008 Dec 15;198(12):1804-8. doi: 10.1086/593214.