Clinical trial NCT00001115: The Effect of Acyclovir Treatment of the Herpes Simplex Virus (HSV) Infection on HIV Levels in the Blood
Official title: A Pilot Study to Determine the Effect of Acyclovir Treatment for Herpes Simplex Virus (HSV) Infection on Peripheral Blood HIV Viral Load.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Herpes Simplex
HIV Infections
Keywords: Herpes Simplex
Acyclovir
Acquired Immunodeficiency Syndrome
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
First posted: 2001-08-31
Enrollment: 75
Sex: ALL
Minimum age (years): 13
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: Part A: To evaluate the impact of HSV suppression with acyclovir ( ACV ) on HIV burden in patients with asymptomatic HSV infection and at high risk for HSV reactivation.

Part B: To characterize the change in plasma HIV RNA levels and other measures of HIV burden during and after a 10 day course of ACV treatment for acute HSV infection.

Approximately 70% of patients infected with HIV are concurrently infected with HSV. There is new evidence to suggest that HSV may act as a co-factor in HIV disease progression. This study will attempt to determine if the upregulation of HIV RNA that occurs during symptomatic HSV reactivation also occurs during asymptomatic HSV reactivation and if suppression of HSV will result in decreased levels of HIV RNA. There is a need to determine the patterns of association between HSV and HIV.

Detailed description: Approximately 70% of patients infected with HIV are concurrently infected with HSV. There is new evidence to suggest that HSV may act as a co-factor in HIV disease progression. This study will attempt to determine if the upregulation of HIV RNA that occurs during symptomatic HSV reactivation also occurs during asymptomatic HSV reactivation and if suppression of HSV will result in decreased levels of HIV RNA. There is a need to determine the patterns of association between HSV and HIV.

Part A: 60 approved HIV infected patients will be randomized to either suppressive ACV therapy or matching placebo for 12 weeks. Serology for HSV serum antibodies will be obtained at screening and a full history and physical exam will be performed on Day 1 and interval examinations at Weeks 2, 4, 8 and 12. Extensive clinical exams will be conducted on a regular schedule throughout the 12 weeks.

Part B: 15 approved HIV infected patients will receive treatment with ACV until resolution of the lesion. All patients will be monitored on Day 9-12 of ACV therapy for crusting and resolutions of HSV lesions and will be followed for 3.5 months.

AS PER AMENDMENT 3/11/97: Noncommercial active acyclovir will be made available for Part A patients wo develop acute HSV while on study and for Part B patients who develop acute HSV after completion of the acute phase of treatment ( i.e., during the follow-up phase).

Eligibility criteria: Inclusion Criteria

Patients must have:

Parts A and B:

* Documented HIV infection.
* Patients \>= 18 years of age must be willing and able to give informed consent and patients \< 18 years must have written consent from a parent or guardian.

Part A:

* CD4+ T count \< 250 cells/mm3 within 1 month prior to study entry.
* Documented antibodies to HSV any time prior to study.
* History of HSV outbreak in past 2 to 12 months.
* Former Part B patients who have completed the 12 week follow up may enter Part A after at least a 4-week washout.

Part B:

* Documented CD4+ T count \< 250 cells/mm3 anytime prior to study entry.
* Oral, genital or anorectal lesions with a vesiculopustular component.
* Presumptive diagnosis of HSV.
* Former part A patients may enter part B after a 4-week washout.

Exclusion Criteria

Patients with any of the following prior conditions are excluded:

* Documented or suspected HSV within 2 months prior to study entry.
* History of infection with an acyclovir resistant HSV strain.
* History of disseminated HSV.
* History of treatment for acute CMV or MAC disease.
* History of poor medication or clinic visit compliance.

Prior Medication:

Excluded:

* Use of acyclovir, famciclovir, foscarnet, ganciclovir, valacyclovir or cidofovir for any reason within one month prior to study entry. \[AS PER AMENDMENT 1/21/97: Use of antiherpes agents, both FDA-approved and investigational, including bis-POM, PMEA, lobucavir, acyclovir, etc.\]
* Initiation or modification of antiretroviral therapy, immunomodulators, or any kind of vaccination within 2 months prior to study entry.
* Treatment for acute medical condition within 4 weeks prior to study entry.

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Palo Alto
country: United States
facility: AIDS Research Ctr
state: California
city: Torrance
country: United States
facility: Harbor-UCLA Med Ctr
state: California
city: New Haven
country: United States
facility: Yale Univ School of Medicine / AIDS Program
state: Connecticut
city: Fort Lauderdale
country: United States
facility: North Broward Hosp District
state: Florida
city: Miami
country: United States
facility: Univ of Miami / Jackson Memorial Hosp
state: Florida
city: Chicago
country: United States
facility: Univ of Illinois - Chicago
state: Illinois
city: Chicago
country: United States
facility: Univ of Illinois Chicago / Howard Brown Hlth Ctr
state: Illinois
city: Baltimore
country: United States
facility: Johns Hopkins Univ
state: Maryland
city: Brooklyn
country: United States
facility: SUNY Brooklyn / SUNY Health Sciences Ctr at Brooklyn
state: New York
city: New York
country: United States
facility: Community Research Initiative on AIDS
state: New York
city: New York
country: United States
facility: NYU - Bellevue Hosp
state: New York
city: Valhalla
country: United States
facility: New York Med College / Westchester County Med Ctr
state: New York
city: Portland
country: United States
facility: Research and Education Group
state: Oregon
city: Philadelphia
country: United States
facility: Univ of Pennsylvania Med Ctr
state: Pennsylvania
city: Providence
country: United States
facility: Brown Univ / The Miriam Hosp
state: Rhode Island
Study officials:
name: Cohn J
role: STUDY_CHAIR
name: Mole L
role: STUDY_CHAIR
References: