Antiviral Activity of and Resistance to Lamivudine in Combination With Zidovudine, Stavudine, or Didanosine
Information source: National Institute of Allergy and Infectious Diseases (NIAID)
Information obtained from ClinicalTrials.gov on June 20, 2008
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: HIV Infections
Intervention: Lamivudine (Drug); Stavudine (Drug); Zidovudine (Drug); Didanosine (Drug)
Phase: Phase 2
Status: Completed
Sponsored by: National Institute of Allergy and Infectious Diseases (NIAID) Official(s) and/or principal investigator(s):
Kuritzkes D, Study Chair
Johnson V, Study Chair
Summary
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.
Clinical Details
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
Study design: Treatment
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
Minimum age: 12 Years.
Maximum age: N/A.
Gender(s): Both.
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.
Locations and Contacts
Univ of Puerto Rico, San Juan 009365067, Puerto Rico
Univ of California / San Diego Treatment Ctr, San Diego, California 921036325, United States
Stanford at Kaiser / Kaiser Permanente Med Ctr, San Francisco, California 94115, United States
UCLA CARE Ctr, Los Angeles, California 90095, United States
San Mateo AIDS Program / Stanford Univ, Stanford, California 943055107, United States
Santa Clara Valley Med Ctr / AIDS Community Rsch Consortium, San Jose, California 951282699, United States
Univ of Colorado Health Sciences Ctr, Denver, Colorado 80262, United States
Univ of Miami School of Medicine, Miami, Florida 331361013, United States
Queens Med Ctr, Honolulu, Hawaii 96816, United States
Univ of Hawaii, Honolulu, Hawaii 96816, United States
Rush Presbyterian - Saint Luke's Med Ctr, Chicago, Illinois 60612, United States
Cook County Hosp, Chicago, Illinois 60612, United States
Illinois Masonic Med Ctr, Chicago, Illinois 606575147, United States
Louis A Weiss Memorial Hosp, Chicago, Illinois 60640, United States
Indiana Univ Hosp, Indianapolis, Indiana 462025250, United States
Methodist Hosp of Indiana / Life Care Clinic, Indianapolis, Indiana 46202, United States
Johns Hopkins Hosp, Baltimore, Maryland 21287, United States
State of MD Div of Corrections / Johns Hopkins Univ Hosp, Baltimore, Maryland 212052196, United States
Beth Israel Deaconess - West Campus, Boston, Massachusetts 02215, United States
St Louis Regional Hosp / St Louis Regional Med Ctr, St. Louis, Missouri 63112, United States
Bellevue Hosp / New York Univ Med Ctr, New York, New York 10016, United States
SUNY / Erie County Med Ctr at Buffalo, Buffalo, New York 14215, United States
Beth Israel Med Ctr, New York, New York 10003, United States
Moses H Cone Memorial Hosp, Greensboro, North Carolina 27401, United States
Ohio State Univ Hosp Clinic, Columbus, Ohio 432101228, United States
MetroHealth Med Ctr, Cleveland, Ohio 441091998, United States
Univ of Pennsylvania at Philadelphia, Philadelphia, Pennsylvania 19104, United States
Julio Arroyo, West Columbia, South Carolina 29169, United States
Vanderbilt Univ Med Ctr, Nashville, Tennessee 37203, United States
Univ of Washington, Seattle, Washington 981224304, United States
Additional Information
Click here for more information about zidovudine Click here for more information about didanosine Click here for more information about stavudine Click here for more information about lamivudine
Related 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.
Last updated: June 23, 2005
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