Safety and Effectiveness of Combining Hydroxyurea (HU) With Didanosine (ddI) and Stavudine (d4T) for Treatment of HIV-Infected Adults

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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A Phase I/II Study of the Safety and Antiretroviral Activity of Nine Hydroxyurea Regimens in Combination With ddI and d4T in Subjects With HIV Infection

Conditions
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HIV Infections

Intervention / Treatment
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* Drug: Hydroxyurea
* Drug: Stavudine
* Drug: Didanosine


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Factorial Assignment


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Hydroxyurea|nan|
|Drug: Stavudine|nan|
|Drug: Didanosine|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Didanosine, Dose-Response Relationship, Drug, Drug Therapy, Combination, Stavudine, Hydroxyurea, Reverse Transcriptase Inhibitors, Anti-HIV Agents