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Sponsored by: |
National Institute of Allergy and Infectious Diseases (NIAID) |
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Information provided by: | National Institute of Allergy and Infectious Diseases (NIAID) |
ClinicalTrials.gov Identifier: | NCT00000919 |
The purpose of this study is to compare the effectiveness of various combinations of anti-HIV drugs in HIV-positive men and women. Patients receive specific combinations of 3 or 4 of the following 6 drugs: didanosine (ddI), stavudine (d4T) efavirenz (EFV), nelfinavir (NFV), lamivudine (3TC), or zidovudine (ZDV). Anti-HIV therapy is effective in preventing the spread of HIV in the body. However, patients often experience unpleasant side effects and have difficulties following the dosing schedule. This study looks for combinations of anti-HIV drugs ("cocktails") which will be the most effective with the fewest problems.
Condition | Intervention |
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HIV Infections |
Drug: Indinavir sulfate Drug: Lamivudine/Zidovudine Drug: Ritonavir Drug: Hydroxyurea Drug: Abacavir sulfate Drug: Amprenavir Drug: Nelfinavir mesylate Drug: Efavirenz Drug: Lamivudine Drug: Stavudine Drug: Zidovudine Drug: Didanosine |
Study Type: | Interventional |
Study Design: | Treatment, Double-Blind, Pharmacokinetics Study |
Official Title: | Study of Protease Inhibitor and/or Non-Nucleoside Reverse Transcriptase Inhibitor With Dual Nucleosides in Initial Therapy of HIV Infection |
Estimated Enrollment: | 900 |
Highly active antiretroviral therapy, though effective in the suppression of HIV proliferation, is often complicated by difficulties with adherence and drug toxicity. Various combinations of highly active antiretroviral therapy exist; all have proved efficacious in related trials. The question addressed in this trial is which combination of antiretroviral "cocktails" provides the single greatest advantage in preventing the spread of HIV in the body. In effect, which therapy provides the greatest benefit with the fewest complications.
Step 1: Patients are randomized to 1 of 6 arms:
Arm A: didanosine (ddI), stavudine (d4T), efavirenz (EFV), and nelfinavir (NFV) placebo.
Arm B: ddI, d4T, EFV placebo, and NFV. Arm C: lamivudine (3TC)/zidovudine (ZDV), EFV, and NFV placebo. Arm D: 3TC/ZDV, EFV placebo, and NFV. Arm E: ddI, d4T, EFV, and NFV. Arm F: 3TC/ZDV, EFV, and NFV. Patients with virologic failure on 2 successive measurements or study-drug intolerance discontinue their randomized study therapy and proceed to Step 2.
[AS PER AMENDMENT 7/5/00: Patients must switch regimens as soon as possible after confirmation of virologic failure to prevent development of drug resistance.]
Step 2:
Arm A: Patients receive treatment as in Arm D of Step 1. Arm B: Patients receive treatment as in Arm C of Step 1. Arm C: Patients receive treatment as in Arm B of Step 1. Arm D: Patients receive treatment as in Arm A of Step 1. Arms A, B, C, and D: Patients who fail Step 2 treatment proceed to Step 3. Arms E and F: Patients with virologic failure on Step 1 proceed immediately to Step 3.
Step 3 (salvage therapy):
Arm A, B, C, and D: Patients receive indinavir (IDV), amprenavir (APV), ddI, and hydroxyurea (HU).
[AS PER AMENDMENT 7/5/00: Patients now receive treatment on Regimen 1, 2, 3, 4, 5, or 6. Regimen 1 consists of IDV, ritonavir (RTV), ddI, and HU. Regimen 2 consists of APV, RTV, ddI, and HU. Regimen 3 consists of IDV, RTV, abacavir (ABC), and 3TC/ZDV. Regimen 4 consists of APV, RTV, ABC, and 3TC/ZDV.
Regimen 5 consists of IDV, RTV, ABC, d4T, and 3TC. Regimen 6 consists of APV, RTV, ABC, d4T, and 3TC.] Arm E: Patients receive IDV, APV, and 3TC/ZDV. [AS PER AMENDMENT 7/5/00: Patients now receive treatment on Regimen 7 or 8. Regimen 7 consists of IDV, RTV, and 3TC/ZDV. Regimen 8 consists of APV, RTV, and 3TC/ZDV.] Arm F: Patients receive IDV, APV, ddI, and d4T. [AS PER AMENDMENT 7/5/00: Patients now receive treatment on Regimen 9 or 10. Regimen 9 consists of IDV, RTV, ddI, and d4T. Regimen 10 consists of APV, RTV, ddI, and d4T.] [AS PER AMENDMENT 7/5/00: Patients already enrolled in Step 3 before site registration to Version 4.0 of this protocol have the option of receiving 1 of the appropriate new Step 3 regimens as outlined above or staying on their originally assigned Step 3 therapy.] [AS PER AMENDMENT 3/21/01: If virologic failure on Step 1 or 2 is confirmed, then HIV-1 RNA genotype resistance testing (in real-time, if possible) is performed. Patients receive 1 of the Step 3 drug regimens based on the results of the resistance testing.] Patients may co-enroll in metabolic, pharmacologic, immunologic, or adherence substudies.
Ages Eligible for Study: | 13 Years and older |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | No |
Inclusion Criteria
Concurrent Medication:
[Required: AS PER AMENDMENT 7/5/00:
[Suggested as an alternative agent for chemoprophylaxis against Mycobacterium avium complex:
[Allowed: AS PER AMENDMENT 7/5/00:
[Allowed with caution: AS PER AMENDMENT 7/5/00:
Medications that interact with PIs as substrates, inhibitors, or inducers, including, but not limited to:
NOTE:
[Allowed with extreme caution:
ddI, as clinically indicated in patients with known risk factors, including, but not limited to, alcohol abuse, morbid obesity, hypertriglyceridemia, cholelithiasis, endoscopic retrograde cholangiopancreatography, use of medications known to cause pancreatitis (e.g., pentamidine) and use of medications known or thought to increase exposure to ddI (e.g., HU, allopurinol).]
Concurrent Treatment:
[Allowed:
Acupuncture and visualization techniques.]
Patients must have:
[AS PER AMENDMENT 9/9/99:
Risk Behavior:
[Allowed with caution:
Alcoholic beverages.]
Exclusion Criteria
Co-existing Condition:
Patients with the following condition are excluded:
AIDS-related malignancy other than minimal Kaposi's sarcoma.
Concurrent Medication:
[Excluded:
Patients with the following prior conditions are excluded:
Prior Medication:
Excluded:
[AS PER AMENDMENT 5/5/99:
Prior Treatment:
Excluded:
[AS PER AMENDMENT 5/5/99:
Risk Behavior:
Excluded:
Study Chair: | Robert Shafer | |
Study Chair: | Gregory Robbins |
Study ID Numbers: | ACTG 384, AACTG A5005s, AACTG A5006s, AACTG A5007s, AACTG A5031s, AACTG 731 |
Study First Received: | November 2, 1999 |
Last Updated: | July 31, 2007 |
ClinicalTrials.gov Identifier: | NCT00000919 History of Changes |
Health Authority: | United States: Federal Government |
HIV Protease Inhibitors Reverse Transcriptase Inhibitors Anti-HIV Agents Viral Load |
Antimetabolites Sexually Transmitted Diseases, Viral Stavudine Indinavir Hydroxyurea Lamivudine Zidovudine Reverse Transcriptase Inhibitors Anti-Bacterial Agents Amprenavir Anti-Retroviral Agents Abacavir Nelfinavir Retroviridae Infections |
Efavirenz HIV Protease Inhibitors Anti-HIV Agents Acquired Immunodeficiency Syndrome Antiviral Agents Immunologic Deficiency Syndromes Protease Inhibitors Virus Diseases Didanosine HIV Infections Ritonavir Sexually Transmitted Diseases Antitubercular Agents |
Antimetabolites Anti-Infective Agents Communicable Diseases Sexually Transmitted Diseases, Viral Slow Virus Diseases Indinavir Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Hydroxyurea Hematologic Agents Zidovudine Lamivudine Infection Reverse Transcriptase Inhibitors Anti-Bacterial Agents |
Amprenavir Anti-Retroviral Agents Therapeutic Uses Abacavir Nelfinavir Retroviridae Infections Nucleic Acid Synthesis Inhibitors HIV Protease Inhibitors RNA Virus Infections Antisickling Agents Anti-HIV Agents Immune System Diseases Acquired Immunodeficiency Syndrome Enzyme Inhibitors Antiviral Agents |