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Antiviral Activity of and Resistance to Lamivudine in Combination With Zidovudine, Stavudine, or Didanosine
This study has been completed.
Sponsored by: National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00000838
  Purpose

To evaluate the efficacy, safety, and pharmacokinetics of lamivudine (3TC) combined with zidovudine (AZT), stavudine (d4T), or didanosine (ddI) in comparison with d4T or ddI monotherapy in HIV-infected patients with no prior nucleoside therapy.

3TC may be uniquely effective in combination with AZT due to the interaction of AZT and 3TC resistance mutations. One explanation is that the M184V mutation, which confers resistance to 3TC, suppresses AZT resistance. This benefit of 3TC may not extend to combination therapy with other nucleoside analogs.


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

MedlinePlus related topics: AIDS
Drug Information available for: Zidovudine Lamivudine Didanosine Stavudine
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment
Official Title: A Phase II, Randomized Study of the Antiviral Activity and Resistance Interactions of Lamivudine (3TC) in Combination With Zidovudine (AZT), Stavudine (d4T), or Didanosine (ddI) Versus Monotherapy With ddI or d4T in HIV-Infected Individuals With 200 - 600 CD4+ Cells/mm3 and No Previous Nucleoside Experience

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

Estimated Enrollment: 256
Detailed Description:

3TC may be uniquely effective in combination with AZT due to the interaction of AZT and 3TC resistance mutations. One explanation is that the M184V mutation, which confers resistance to 3TC, suppresses AZT resistance. This benefit of 3TC may not extend to combination therapy with other nucleoside analogs.

Patients are randomized to either a ddI limb or d4T limb, then randomized a second time to one of six treatment arms, as follows: ddI alone, d4T alone, 3TC/AZT (on both ddI and d4T limbs), 3TC/ddI, and 3TC/d4T. Treatment is given for 48 weeks. At study week 24, patients on monotherapy will have 3TC added to their regimen (in a blinded fashion).

PER AMENDMENT 10/18/96: A treatment extension phase has been added to the study design in order to allow subjects who complete 48 weeks of therapy to remain on their same blinded treatment until approximately 2 months after the last enrolled subject completes 48 weeks on the study.

  Eligibility

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

Inclusion Criteria

Concurrent Medication:

Allowed:

  • PCP prophylaxis.

Patients must have:

  • HIV infection.
  • CD4 count 200 - 600 cells/mm3.
  • Life expectancy of at least 24 weeks.
  • Consent of parent or guardian if less than 18 years old.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms or conditions are excluded:

  • Unexplained temperature >= 38.5 C for 7 consecutive days within 30 days prior to study entry.

PER AMENDMENT 1/25/96:

  • A malignancy that requires systemic chemotherapies other than Kaposi's sarcoma.

Concurrent Medication:

Excluded:

  • Concurrent other antiretroviral or immunologic agents.
  • Other experimental therapies.
  • Systemic corticosteroids (except as adjuvant therapy for acute PCP) and other immunosuppressive drugs.
  • Systemic cytotoxic chemotherapy.
  • Induction or maintenance with foscarnet or ganciclovir (oral or IV).

Patients with the following prior conditions are excluded:

  • History of acute or chronic pancreatitis.
  • History of grade 2 or higher peripheral neuropathy.

Prior Medication:

Excluded:

  • Antiretrovirals within 90 days prior to study entry.
  • More than 7 days total lifetime use of any antiretroviral nucleoside.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00000838

  Show 30 Study Locations
Sponsors and Collaborators
Investigators
Study Chair: Kuritzkes D
Study Chair: Johnson V
  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
Click here for more information about lamivudine  This link exits the ClinicalTrials.gov site

Publications:
Marschner I, Betensky RA, Degruttola V, Kuritzkes DR. Biases in the assessment of viral load reduction in HIV clinical trials. Int Conf AIDS. 1998;12:802 (abstract no 42149)
Hill A, Demasi R, Kuhn M. Different analyses give highly variable estimates of HIV-1 RNA undetectability and log reduction in clinical trials. Int Conf AIDS. 1998;12:813-4 (abstract no 42204)
Kuritzkes DR, Marschner IC, Johnson VA, Bassett RL, Eron JJ, Fischl MA, Boone G, Skovronski J, Wood K, Bell DL, Pettinelli CB, Sommadossi JP. A randomized, double-blind, placebo-controlled trial of lamivudine (3TC) in combination with zidovudine (ZDV), stavudine (d4T), or didanosine (ddI) in treatment naive patients. Conf Retroviruses Opportunistic Infect. 1998 Feb 1-5;5th:79 (abstract no 1)
Kuritzkes DR, Marschner I, Johnson VA, Bassett R, Eron JJ, Fischl MA, Murphy RL, Fife K, Maenza J, Rosandich ME, Bell D, Wood K, Sommadossi JP, Pettinelli C. Lamivudine in combination with zidovudine, stavudine, or didanosine in patients with HIV-1 infection. A randomized, double-blind, placebo-controlled trial. National Institute of Allergy and Infectious Disease AIDS Clinical Trials Group Protocol 306 Investigators. AIDS. 1999 Apr 16;13(6):685-94.
For the Adult ACTG Protocol 306 370 Teams. Rate of Thymidine Analogue Resistance Mutation Accumulation With Zidovudine- or Stavudine-Based Regimens. J Acquir Immune Defic Syndr. 2004 Apr 20;36(1):600-603.
Fisher M. Nucleoside combinations for antiretroviral therapy: efficacy of stavudine in combination with either didanosine or lamivudine. AIDS. 1998;12 Suppl 3:S9-16.

Study ID Numbers: ACTG 306
Study First Received: November 2, 1999
Last Updated: August 22, 2008
ClinicalTrials.gov Identifier: NCT00000838  
Health Authority: United States: Federal Government

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

Study placed in the following topic categories:
Virus Diseases
Sexually Transmitted Diseases, Viral
Stavudine
Didanosine
HIV Infections
Sexually Transmitted Diseases
Acquired Immunodeficiency Syndrome
Lamivudine
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