The purpose of this study is to compare the safety and effectiveness of 9 doses of HU in order to find the best dose of HU to use with ddI and d4T in fighting HIV infection. HU plus ddI plus d4T appears to be a suitable anti-HIV drug combination for long-term control of HIV. This combination can sharply decrease viral load (level of HIV in the body) with few side effects, making it easy to take.

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

Further Study Details: 

Expected Total Enrollment:  225

The combination of HU plus ddI plus d4T appears to be suitable for long-term control of HIV in that it: (1) has a novel resistance/rebound profile demonstrating virus suppression even in the presence of ddI-resistant mutants; (2) can produce a pronounced fall in viral load; and (3) is well tolerated (over 200 patients have been treated for up to 3 years with minimal side effects).

Patients are stratified by antiretroviral experience: naive (no more than 2 weeks of therapy) versus experienced (more than 2 weeks). Patients must discontinue all antiretroviral therapy for at least 28 days prior to randomization to 1 of 9 HU treatment arms. Treatment arms are divided into 3 HU dose categories: very low, low, and medium. Within each category HU is administered daily on 3 different dosing schedules. Depending on viral load, patients on the very low and low dose arms may have the opportunity to intensify their HU dose at any time beyond Week 12, provided no Grade 3 or 4 HU-related toxicity is present (these patients are monitored for an additional 8 weeks following intensification). All patients receive ddI and d4T at the same doses every day. When 50% of patients have completed 24 weeks of treatment, an analysis is made to determine whether or not to continue the 52-week study without modifications. Patients are monitored periodically for changes in plasma HIV RNA, CD4 cell counts, weight, and symptoms.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

Inclusion Criteria

Patients may be eligible for this study if they:

• Are HIV-positive.
• Have a viral load of 5,000 to 100,000 copies/ml.
• Are willing to stop all anti-HIV medications for at least 28 days before receiving study drugs.
• Are at least 18 years old.

Exclusion Criteria

Patients will not be eligible for this study if they:

• Have a history of opportunistic (AIDS-related) infection.
• Have a history of pancreatitis or other serious condition.
• Have any cancer that will require chemotherapy within the next 24 weeks.
• Are allergic to ddI or d4T.
• Have received an HIV vaccine within 28 days of study entry.
• Have received a red blood cell transfusion within the past 60 days, or have had repeated transfusions at any time in the past.
• Abuse alcohol or drugs.
• Have received certain medications.

California
      AIDS Healthcare Foundation, Los Angeles,  California,  90027,  United States
      San Francisco VA Med Ctr, San Francisco,  California,  94121,  United States
Connecticut
      Gary Blick MD, Stamford,  Connecticut,  06901,  United States
District of Columbia
      Dr Bruce Rashbaum, Washington,  District of Columbia,  20037,  United States
Florida
      IDC Research Initiative, Altamonte Springs,  Florida,  32701,  United States
      Boulevard Comprehensive Care Ctr, Jacksonville,  Florida,  32209,  United States
      Center for Quality Care, Tampa,  Florida,  33609,  United States
Georgia
      AIDS Research Consortium of Atlanta Inc, Atlanta,  Georgia,  30308,  United States
Massachusetts
      New England Med Ctr, Boston,  Massachusetts,  02111,  United States
New York
      Albany Med College, Albany,  New York,  122083479,  United States
      Mt Vernon Hosp, Mt. Vernon,  New York,  10550,  United States
Pennsylvania
      Univ of Pennsylvania Med Ctr, Philadelphia,  Pennsylvania,  19104,  United States
      Thomas Jefferson Univ, Philadelphia,  Pennsylvania,  19107,  United States
South Carolina
      Coastal Carolina Research Ctr, Mount Pleasant,  South Carolina,  29464,  United States
Texas
      Univ of Texas Southwestern Med Ctr of Dallas, Dallas,  Texas,  75235,  United States
      Univ of Texas Med Branch, Galveston,  Texas,  775550835,  United States
      Montrose Clinic, Houston,  Texas,  77006,  United States
Washington
      Swedish Med Ctr, Seattle,  Washington,  98122,  United States

Study chairs or principal investigators

Franco Lori,  Study Chair
Julianna Lisziewicz,  Study Chair

Study ID Numbers:  304A; RIGHT 702
Record last reviewed:  August 2000
Last Updated:  October 13, 2004
Record first received:  November 2, 1999
ClinicalTrials.gov Identifier:  NCT00002427
Health Authority: United States: Food and Drug Administration
ClinicalTrials.gov processed this record on 2005-04-08