This study will look at different anti-HIV drug regimens to see which works best to keep the level of HIV (viral load) in the blood as low as possible during maintenance therapy. You will be assigned randomly (like tossing a coin) to 1 of 3 groups: Group 1: Didanosine plus stavudine plus hydroxyurea (ddI/d4T/HU). Group 2: Didanosine plus stavudine plus efavirenz (ddI/d4T/EFV). Group 3: This group of patients will remain on their current drug regimens. This study will last approximately 3 years; you will receive study medications for the duration of the study. Anti-HIV drug regimens that include protease inhibitors (PIs) are very good at lowering viral load. However, some patients have a rise in HIV levels while on PI maintenance. It may be possible to keep HIV levels low using another class of drugs for maintenance that are easier to take and less expensive than PIs. If viral load increases while a patient is taking this second group of drugs, it may be possible to restart the PI drug regimen and again decrease HIV levels.

Condition	Treatment or Intervention	Phase
HIV Infections	Drug: Hydroxyurea  Drug: Efavirenz  Drug: Stavudine  Drug: Didanosine	Phase II

Further Study Details: 

Expected Total Enrollment:  150

Combination antiretroviral therapies using protease inhibitors (PIs) are capable of suppressing plasma HIV RNA to undetectable levels. However, approximately 10% of patients who achieve undetectable viral loads will experience a detectable rise in HIV RNA each year. When HIV replication has been suppressed to very low levels, it may be possible to consolidate antiretroviral therapy into a simpler and potentially less toxic "maintenance" regimen without a PI. Such a regimen would ideally be potent enough to continue to maintain viral suppression but use agents that are better tolerated, more easily salvaged, less expensive, and/or more convenient than PI-containing regimens. Subsequent rises in HIV viremia with non-PI maintenance regimens may respond to resumption of the pre-maintenance PI-containing regimen, extending the use of the potent PI class.

Patients are randomized 1:1:1 to treatment with ddI/d4T/HU (Arm A) versus ddI/d4T/EFV (Arm B) versus continuation of the pre-entry PI-containing regimen (Arm C). Viral load is measured at Weeks 1, 2, 4, 8, 12, 16, 20, and 24, then every 8 weeks for up to 3 years. Upon virologic failure (plasma HIV RNA greater than or equal to 200 copies/ml), or drug intolerance, patients on the maintenance regimens (Arms A and B) restart their pre-entry PI-containing regimen. Patients on Arm C are managed according to best medical judgment of their primary care provider in the event of virologic failure.

Ages Eligible for Study:  13 Years and above,  Genders Eligible for Study:  Both

Criteria

Inclusion Criteria

You may be eligible for this study if you:

• Are at least 13 years old (need consent if under 18).
• Are HIV-positive.
• Are taking your first anti-HIV drug regimen, which must include a PI and at least one NRTI (nucleoside reverse transcriptase inhibitor) and have been on this regimen for at least 12 months.
• Have a viral load less than 400 copies/ml for at least 12 months prior to study entry, and have a viral load less than 50 copies/ml within 60 days of study entry.
• Have a CD4 cell count of at least 200 cells/mm3 within 60 days of study entry.
• Are willing to go back on the drugs you are currently on, if necessary.
• Are willing to use effective methods of birth control during the study and for 3 months after.

Exclusion Criteria

You will not be eligible for this study if you:

• Have taken ddI, d4T, or HU for more than 2 weeks.
• Have taken any NNRTI (non-nucleoside reverse transcriptase inhibitor) for more than 7 days.
• Have ever taken EFV.
• Have received an HIV vaccine within 30 days prior to study entry.
• Have an AIDS-related cancer that requires chemotherapy.
• Have or have had pancreatic disease.
• Are being treated for a significant illness.
• Abuse drugs or alcohol.
• Are pregnant or breast-feeding.
• Are allergic to any study drugs.
• Have received certain medications.

California
      Stanford Univ Med Ctr, Stanford,  California,  943055107,  United States
      San Mateo AIDS Program / Stanford Univ, Stanford,  California,  943055107,  United States
      Santa Clara Valley Med Ctr / AIDS Community Rsch Consortium, San Jose,  California,  951282699,  United States
      Willow Clinic, Menlo Park,  California,  94025,  United States
Florida
      Univ of Miami School of Medicine, Miami,  Florida,  331361013,  United States
Indiana
      Indiana Univ Hosp, Indianapolis,  Indiana,  462025250,  United States
      Methodist Hosp of Indiana / Life Care Clinic, Indianapolis,  Indiana,  46202,  United States
      Division of Inf Diseases/ Indiana Univ Hosp, Indianapolis,  Indiana,  46202,  United States
Massachusetts
      Harvard (Massachusetts Gen Hosp), Boston,  Massachusetts,  02114,  United States
      Beth Israel Deaconess - West Campus, Boston,  Massachusetts,  02215,  United States
New York
      Univ of Rochester Medical Center, Rochester,  New York,  14642,  United States
      Bellevue Hosp / New York Univ Med Ctr, New York,  New York,  10016,  United States
      Cornell Univ Med Ctr, New York,  New York,  10021,  United States
      Beth Israel Med Ctr, New York,  New York,  10003,  United States
      Chelsea Ctr, New York,  New York,  10021,  United States
North Carolina
      Univ of North Carolina, Chapel Hill,  North Carolina,  275997215,  United States
Ohio
      Univ of Cincinnati, Cincinnati,  Ohio,  452670405,  United States
      Ohio State Univ Hosp Clinic, Columbus,  Ohio,  432101228,  United States
Pennsylvania
      Univ of Pennsylvania at Philadelphia, Philadelphia,  Pennsylvania,  19104,  United States

Study chairs or principal investigators

David Wohl,  Study Chair
Joe Eron,  Study Chair
Roy Gulick,  Study Chair

Study ID Numbers:  ACTG A5039
Record last reviewed:  June 2003
Last Updated:  April 7, 2005
Record first received:  November 2, 1999
ClinicalTrials.gov Identifier:  NCT00000939
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08