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Antiviral Activity of and Resistance to Lamivudine in Combination With Zidovudine, Stavudine, or Didanosine
This study has been completed.
First Received: November 2, 1999   Last Updated: August 22, 2008   History of Changes
Sponsor: 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

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

Resource links provided by NLM:


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

  Hide Study Locations
Locations
United States, California
Univ of California / San Diego Treatment Ctr
San Diego, California, United States, 921036325
Stanford at Kaiser / Kaiser Permanente Med Ctr
San Francisco, California, United States, 94115
UCLA CARE Ctr
Los Angeles, California, United States, 90095
San Mateo AIDS Program / Stanford Univ
Stanford, California, United States, 943055107
Santa Clara Valley Med Ctr / AIDS Community Rsch Consortium
San Jose, California, United States, 951282699
United States, Colorado
Univ of Colorado Health Sciences Ctr
Denver, Colorado, United States, 80262
United States, Florida
Univ of Miami School of Medicine
Miami, Florida, United States, 331361013
United States, Hawaii
Queens Med Ctr
Honolulu, Hawaii, United States, 96816
Univ of Hawaii
Honolulu, Hawaii, United States, 96816
United States, Illinois
Rush Presbyterian - Saint Luke's Med Ctr
Chicago, Illinois, United States, 60612
Cook County Hosp
Chicago, Illinois, United States, 60612
Illinois Masonic Med Ctr
Chicago, Illinois, United States, 606575147
Louis A Weiss Memorial Hosp
Chicago, Illinois, United States, 60640
United States, Indiana
Indiana Univ Hosp
Indianapolis, Indiana, United States, 462025250
Methodist Hosp of Indiana / Life Care Clinic
Indianapolis, Indiana, United States, 46202
United States, Maryland
Johns Hopkins Hosp
Baltimore, Maryland, United States, 21287
State of MD Div of Corrections / Johns Hopkins Univ Hosp
Baltimore, Maryland, United States, 212052196
United States, Massachusetts
Beth Israel Deaconess - West Campus
Boston, Massachusetts, United States, 02215
United States, Missouri
St Louis Regional Hosp / St Louis Regional Med Ctr
St Louis, Missouri, United States, 63112
United States, New York
Bellevue Hosp / New York Univ Med Ctr
New York, New York, United States, 10016
SUNY / Erie County Med Ctr at Buffalo
Buffalo, New York, United States, 14215
Beth Israel Med Ctr
New York, New York, United States, 10003
United States, North Carolina
Moses H Cone Memorial Hosp
Greensboro, North Carolina, United States, 27401
United States, Ohio
Ohio State Univ Hosp Clinic
Columbus, Ohio, United States, 432101228
MetroHealth Med Ctr
Cleveland, Ohio, United States, 441091998
United States, Pennsylvania
Univ of Pennsylvania at Philadelphia
Philadelphia, Pennsylvania, United States, 19104
United States, South Carolina
Julio Arroyo
West Columbia, South Carolina, United States, 29169
United States, Tennessee
Vanderbilt Univ Med Ctr
Nashville, Tennessee, United States, 37203
United States, Washington
Univ of Washington
Seattle, Washington, United States, 981224304
Puerto Rico
Univ of Puerto Rico
San Juan, Puerto Rico, 009365067
Sponsors and Collaborators
Investigators
Study Chair: Kuritzkes D
Study Chair: Johnson V
  More Information

Additional Information:
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     History of Changes
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

Additional relevant MeSH terms:
Antimetabolites
Anti-Infective Agents
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Stavudine
Molecular Mechanisms of Pharmacological Action
Zidovudine
Lamivudine
Infection
Reverse Transcriptase Inhibitors
Anti-Retroviral Agents
Therapeutic Uses
Retroviridae Infections
Nucleic Acid Synthesis Inhibitors
RNA Virus Infections
Anti-HIV Agents
Immune System Diseases
Acquired Immunodeficiency Syndrome
Enzyme Inhibitors
Antiviral Agents
Immunologic Deficiency Syndromes
Pharmacologic Actions
Virus Diseases
Didanosine
HIV Infections
Sexually Transmitted Diseases
Lentivirus Infections

ClinicalTrials.gov processed this record on November 25, 2009