Clinical trial NCT00000916: A Study of the Safety and Effectiveness of Hydroxyurea in Patients on Potent Antiretroviral Therapy and Who Have Less Than 200 Copies/ml of HIV RNA in Their Blood
Official title: A Phase II, Randomized Study of the Safety and Efficacy of Hydroxyurea in Subjects on Potent Antiretroviral Therapy With Less Than 200 Copies/ml of HIV RNA in the Plasma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: HIV Infections
Keywords: Drug Therapy, Combination
HIV Protease Inhibitors
Hydroxyurea
Reverse Transcriptase Inhibitors
Anti-HIV Agents
Viral Load
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
First posted: 2001-08-31
Enrollment: 399
Sex: ALL
Minimum age (years): 13
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: TREATMENT

Brief summary: This study compares the safety and effectiveness of continuing your current anti-HIV medications to that of adding or switching some of your anti-HIV medications. It will follow the effect of these medication changes, including the addition of hydroxyurea (HU), on long-term viral suppression. Other medications which may be added include didanosine (ddI) and/or stavudine (d4T).

Patients receiving combination antiretroviral therapy with indinavir (IDV), zidovudine (ZDV)(or d4T) and lamivudine (3TC) show viral suppression for two years or more. Discontinuation of one or two of these drugs results in prompt loss of the viral suppression. Other studies show that addition of HU to some reverse transcriptase inhibitor treatments results in increased antiviral effects. This study will provide further information on the effect of adding HU to a treatment regimen with respect to long-term viral suppression.

Detailed description: Previous ACTG studies show that discontinuation of one or two of a three-drug regimen (IDV, ZDV, 3TC) leads to prompt loss of viral suppression in the plasma. In this trial, it will be determined whether adding hydroxyurea (HU) to a suppressive regimen increases long term viral suppression. Important safety information on the tolerance of HU regimen will be characterized in asymptomatic patients with viral suppression.

Patients are equally randomized to one of three arms and receive treatment as follows:Arm A: IDV plus ddI plus d4T plus HU placebo. Arm B: IDV plus ddI plus d4T plus HU. Arm C: IDV plus 3TC/ZDV (or d4T plus 3TC). Patients are monitored every 8 weeks with plasma HIV RNA levels and CD4 cell counts.

Eligibility criteria: Inclusion Criteria

You may be eligible for this study if you:

* Are 13 years or older.
* Have documented HIV-1 infection.
* Are currently receiving combined IDV, ZDV(or D4T), and 3TC for at least 6 consecutive months, resulting in HIV RNA less than 200 copies/ml and CD4 cell count greater than 200 cells/mm3.
* Had a CD4 count greater than 100 cells/mm3 before starting current anti-HIV therapy.
* Are of childbearing age and agree to practice abstinence or use of combined barrier and hormonal methods of birth control during and for 3 months after the study.

Exclusion Criteria

You will not be eligible for this study if you:

* Have taken various medications and have various laboratory results (see technical abstract).
* Have cancer requiring chemotherapy.
* Have an unexplained fever for 7 days or diarrhea for 15 days in the month before the start of the study.
* Had prior peripheral neuropathy or hepatitis.
* Recently underwent radiation, experimental, or infection therapy.
* Are pregnant or breastfeeding.

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Alabama Therapeutics CRS
state: Alabama
city: Palo Alto
country: United States
facility: Stanford CRS
state: California
city: San Diego
country: United States
facility: Ucsd, Avrc Crs
state: California
city: San Mateo
country: United States
facility: San Mateo County AIDS Program
state: California
city: Torrance
country: United States
facility: Harbor-UCLA Med. Ctr. CRS
state: California
city: Aurora
country: United States
facility: University of Colorado Hospital CRS
state: Colorado
city: Miami
country: United States
facility: Univ. of Miami AIDS CRS
state: Florida
city: Honolulu
country: United States
facility: Univ. of Hawaii at Manoa, Leahi Hosp.
state: Hawaii
city: Chicago
country: United States
facility: Northwestern University CRS
state: Illinois
city: Chicago
country: United States
facility: Weiss Memorial Hosp.
state: Illinois
city: Indianapolis
country: United States
facility: Indiana Univ. School of Medicine, Wishard Memorial
state: Indiana
city: Indianapolis
country: United States
facility: Indiana Univ. School of Medicine, Infectious Disease Research Clinic
state: Indiana
city: Iowa City
country: United States
facility: Univ. of Iowa Healthcare, Div. of Infectious Diseases
state: Iowa
city: New Orleans
country: United States
facility: Tulane Hemophilia Treatment Ctr.
state: Louisiana
city: Baltimore
country: United States
facility: Johns Hopkins Adult AIDS CRS
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital ACTG CRS
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Med. Ctr., ACTG CRS
state: Massachusetts
city: Minneapolis
country: United States
facility: University of Minnesota, ACTU
state: Minnesota
city: Saint Louis
country: United States
facility: St. Louis ConnectCare, Infectious Diseases Clinic
state: Missouri
city: Saint Louis
country: United States
facility: Washington U CRS
state: Missouri
city: Omaha
country: United States
facility: Univ. of Nebraska Med. Ctr., Durham Outpatient Ctr.
state: Nebraska
city: New York
country: United States
facility: Beth Israel Med. Ctr. (Mt. Sinai)
state: New York
city: New York
country: United States
facility: NY Univ. HIV/AIDS CRS
state: New York
city: New York
country: United States
facility: Beth Israel Med. Ctr., ACTU
state: New York
city: Rochester
country: United States
facility: Univ. of Rochester ACTG CRS
state: New York
city: Chapel Hill
country: United States
facility: Unc Aids Crs
state: North Carolina
city: Charlotte
country: United States
facility: Carolinas HealthCare System, Carolinas Med. Ctr.
state: North Carolina
city: Greensboro
country: United States
facility: Regional Center for Infectious Disease, Wendover Medical Center CRS
state: North Carolina
city: Cincinnati
country: United States
facility: Univ. of Cincinnati CRS
state: Ohio
city: Cleveland
country: United States
facility: Case CRS
state: Ohio
city: Cleveland
country: United States
facility: MetroHealth CRS
state: Ohio
city: Columbus
country: United States
facility: The Ohio State Univ. AIDS CRS
state: Ohio
city: Philadelphia
country: United States
facility: Hosp. of the Univ. of Pennsylvania CRS
state: Pennsylvania
city: Seattle
country: United States
facility: University of Washington AIDS CRS
state: Washington
Study officials:
name: Havlir D; Richman D
role: STUDY_CHAIR
name: Collier A
role: STUDY_CHAIR
name: Hirsch M
role: STUDY_CHAIR
name: Tebas P
role: STUDY_CHAIR
References:
citation: Havlir DV, Gilbert PB, Bennett K, Collier AC, Hirsch MS, Tebas P, Adams EM, Wheat LJ, Goodwin D, Schnittman S, Holohan MK, Richman DD; ACTG 5025 Study Group. Effects of treatment intensification with hydroxyurea in HIV-infected patients with virologic suppression. AIDS. 2001 Jul 27;15(11):1379-88. doi: 10.1097/00002030-200107270-00007.