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The Effectiveness of Three Drug Combinations in HIV-Infected Patients Who Have Taken Zidovudine for More Than 12 Weeks
This study has been completed.
Sponsors and Collaborators: National Institute of Allergy and Infectious Diseases (NIAID)
Bristol-Myers Squibb
Information provided by: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00001063
  Purpose

To compare the effect of stavudine (d4T) alone or with zidovudine (AZT) versus didanosine (ddI) alone or with AZT on CD4 counts, HIV RNA levels, and viral load in HIV-infected patients [AS PER AMENDMENT 3/21/97: To compare the effects of d4T alone versus ddI alone versus AZT plus ddI]. To compare the safety of d4T/AZT. AS PER AMENDMENT 3/21/97: To evaluate the pharmacokinetic interactions of AZT and d4T both at an extracellular and intracellular level.

Although AZT and ddI can delay the advancement of HIV disease, the benefit of either of these drugs has proven to be only temporary. d4T, a new nucleoside analog with a favorable toxicity profile and demonstrated activity against HIV, offers an additional therapeutic option. It is reasonably assumed that the benefit of an antiretroviral agent in terms of delaying clinical disease progression is directly related to its ability to achieve and sustain viral suppression; thus, this study measures effects on viral load and CD4 count.


Condition Intervention Phase
HIV Infections
Drug: Stavudine
Drug: Zidovudine
Drug: Didanosine
Phase II

MedlinePlus related topics: AIDS
Drug Information available for: Zidovudine Didanosine Stavudine
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment
Official Title: A Phase II Randomized Study of the Virologic and Immunologic Effects of d4T vs Zidovudine Plus d4T vs Zidovudine Plus Ddl in HIV-Infected Patients With CD4 Cell Counts Between 300-600/mm3 and Greater Than 12 Weeks Zidovudine Experience

Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Estimated Enrollment: 200
Detailed Description:

Although AZT and ddI can delay the advancement of HIV disease, the benefit of either of these drugs has proven to be only temporary. d4T, a new nucleoside analog with a favorable toxicity profile and demonstrated activity against HIV, offers an additional therapeutic option. It is reasonably assumed that the benefit of an antiretroviral agent in terms of delaying clinical disease progression is directly related to its ability to achieve and sustain viral suppression; thus, this study measures effects on viral load and CD4 count.

Patients are randomized in a blinded fashion to receive AZT or placebo in combination with open-label d4T or ddI for up to 48 weeks. AS PER AMENDMENT 3/21/97: The study is now composed of three arms: open-label d4T versus open-label ddI plus blinded AZT placebo versus blinded AZT plus open-label ddI. Patients originally assigned to the d4T + AZT arm, which was closed 10/96, will be given the option of discontinuing AZT and remaining on d4T monotherapy or discontinuing all study drugs. In addition, all study participants will be asked to participate in a pharmacology substudy.

  Eligibility

Ages Eligible for Study:   12 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

Concurrent Medication:

Required for patients whose CD4 count falls below 200 cells/mm3:

  • PCP prophylaxis with TMP/SMX, aerosolized pentamidine, or dapsone.

Allowed:

  • Atovaquone, IV pentamidine, trimethoprim-dapsone, clindamycin-primaquine, trimetrexate, or TMP/SMX for acute PCP.
  • Topical antifungals, clotrimazole, ketoconazole, fluconazole, and amphotericin B for mucosal and esophageal candidiasis.
  • Itraconazole.
  • Amphotericin B.
  • Rifabutin.
  • Isoniazid.
  • Pyrazinamide.
  • Clofazimine.
  • Clarithromycin.
  • Azithromycin.
  • Ethambutol.
  • Amikacin.
  • Ciprofloxacin.
  • Ofloxacin.
  • Pyrimethamine.
  • Sulfadiazine.
  • Clindamycin.
  • Ganciclovir.
  • G-CSF.
  • Acyclovir (up to 1000 mg/day).
  • Erythropoietin.
  • Antibiotics for bacterial infections.
  • Antipyretics.
  • Analgesics.
  • Antiemetics.
  • Rifampin.

Concurrent Treatment:

Allowed:

  • Local radiation therapy.

Patients must have:

  • HIV infection.
  • CD4 count 300-600 cells/mm3.
  • More than 12 weeks (was 24 weeks, AMENDED 3/31/96) of total prior AZT ( > 500 mg/day without serious adverse event). Subjects must be actively taking ZDV for at least 4 continuous weeks up to the time of study entry.
  • No prior or current history of AIDS.
  • No active opportunistic infection.
  • Life expectancy of at least 2 years.
  • Consent of patient and parent or guardian if less than 18 years of age.

NOTE:

  • Protocol is approved for prisoner enrollment.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms or conditions are excluded:

  • Malignancy requiring systemic cytotoxic chemotherapy.
  • Serious underlying medical condition other than HIV that would reduce life expectancy to < 2 years.

Concurrent Medication:

Excluded:

  • Antiretrovirals other than study drugs.
  • Foscarnet.

Patients with the following prior conditions are excluded:

  • Unexplained temperature >= 38.5 C for 7 days or chronic diarrhea (>= three stools daily) for 15 days, if occurring within 30 days prior to study entry.
  • History of acute or chronic pancreatitis.
  • History of grade 2 or higher peripheral neuropathy.
  • History of grade 3 or worse intolerance to 500-600 mg/day AZT.

Prior Medication:

Excluded:

(within 30 days prior to study entry)

  • Prior ddI, ddC, 3TC or d4T (more than 2 weeks total).
  • Non-nucleoside reverse transcriptase inhibitor or protease inhibitor.
  • Biologic response modifiers such as interferon and IL-2.
  • Other experimental therapy.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00001063

  Show 51 Study Locations
Sponsors and Collaborators
Bristol-Myers Squibb
Investigators
Study Chair: Havlir D
Study Chair: Richman D
Study Chair: Pollard R
Study Chair: Friedland G
  More Information

Click here for more information about Zidovudine  This link exits the ClinicalTrials.gov site
Click here for more information about Didanosine  This link exits the ClinicalTrials.gov site
Click here for more information about Stavudine  This link exits the ClinicalTrials.gov site

Publications:
[No authors listed] d4T+AZT--unexpected CD4 drop seen in study. AIDS Treat News. 1996 Dec 20;(No 261):1. No abstract available.
Shaefer M, Hardy WD, Shaker-Irwin L, Williams V, Maude C, Thommes J, Graham N. HIV viral load response in subjects switched from zidovudine (ZDV)-containing to stavudine (D4T)-containing regimens in the Pacific Oaks Population Study (POPS). Int Conf AIDS. 1998;12:57 (abstract no 12228)
Havlir DV, Friedland G, Pollard R, Tierney C, Smeaton L, Fox L, Richman DD. Combination zidovudine (ZDV) and stavudine (d4T) therapy versus other nucleosides: report of two randomized trials (ACTG 290 and 298). Conf Retroviruses Opportunistic Infect. 1998 Feb 1-5;5th:79 (abstract no 2)
Cadman J. 2, 4, 6, 8, who's afraid to phosphorylate? GMHC Treat Issues. 1998 Feb;12(2):6-8. No abstract available.
Havlir DV, Tierney C, Friedland GH, Pollard RB, Smeaton L, Sommadossi JP, Fox L, Kessler H, Fife KH, Richman DD. In vivo antagonism with zidovudine plus stavudine combination therapy. J Infect Dis. 2000 Jul;182(1):321-5.
Sommadossi JP, Zhou XJ, Moore J, Havlir DV, Friedland G, Tierney C, Smeaton L, Fox L, Richman D, Pollard R. Impairment of stavudine (d4T) phosphorylation in patients receiving a combination of zidovudine (ZDV) and d4T (ACTG 290). Conf Retroviruses Opportunistic Infect. 1998 Feb 1-5;5th:79 (abstract no 3)

Study ID Numbers: ACTG 290
Study First Received: November 2, 1999
Last Updated: August 1, 2008
ClinicalTrials.gov Identifier: NCT00001063  
Health Authority: United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Didanosine
Drug Therapy, Combination
AIDS-Related Complex
Zidovudine
Stavudine

Study placed in the following topic categories:
Virus Diseases
Sexually Transmitted Diseases, Viral
Stavudine
Didanosine
HIV Infections
Sexually Transmitted Diseases
Acquired Immunodeficiency Syndrome
Zidovudine
AIDS-Related Complex
Retroviridae Infections
Immunologic Deficiency Syndromes

Additional relevant MeSH terms:
Antimetabolites
Anti-Infective Agents
RNA Virus Infections
Anti-HIV Agents
Slow Virus Diseases
Immune System Diseases
Molecular Mechanisms of Pharmacological Action
Enzyme Inhibitors
Infection
Antiviral Agents
Pharmacologic Actions
Reverse Transcriptase Inhibitors
Anti-Retroviral Agents
Therapeutic Uses
Lentivirus Infections
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on January 15, 2009