Antiviral Activity of and Resistance to Lamivudine in Combination With Zidovudine, Stavudine, or Didanosine
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
2 other identifiers
interventional
256
2 countries
32
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2 hiv-infections
32 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Completion
Last participant's last visit for all outcomes
March 1, 1998
CompletedFirst Submitted
Initial submission to the registry
November 2, 1999
CompletedFirst Posted
Study publicly available on registry
August 31, 2001
CompletedNovember 4, 2021
October 1, 2021
November 2, 1999
October 27, 2021
Conditions
Keywords
Interventions
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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.
- +4 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (32)
Alabama Therapeutics CRS
Birmingham, Alabama, United States
UCLA CARE Center CRS
Los Angeles, California, 90095, United States
Stanford CRS
Palo Alto, California, 94115, United States
Ucsd, Avrc Crs
San Diego, California, 92103, United States
Santa Clara Valley Med. Ctr.
San Jose, California, 95128, United States
San Mateo County AIDS Program
San Mateo, California, United States
University of Colorado Hospital CRS
Aurora, Colorado, 80262, United States
Univ. of Miami AIDS CRS
Miami, Florida, 33136, United States
Queens Med. Ctr.
Honolulu, Hawaii, 96816, United States
Univ. of Hawaii at Manoa, Leahi Hosp.
Honolulu, Hawaii, 96816, United States
Cook County Hosp. CORE Ctr.
Chicago, Illinois, 60612, United States
Rush Univ. Med. Ctr. ACTG CRS
Chicago, Illinois, 60612, United States
Weiss Memorial Hosp.
Chicago, Illinois, 60640, United States
Northwestern University CRS
Chicago, Illinois, United States
Indiana Univ. School of Medicine, Infectious Disease Research Clinic
Indianapolis, Indiana, 46202, United States
Methodist Hosp. of Indiana
Indianapolis, Indiana, 46202, United States
Johns Hopkins Adult AIDS CRS
Baltimore, Maryland, 21287, United States
Beth Israel Deaconess Med. Ctr., ACTG CRS
Boston, Massachusetts, United States
St. Louis ConnectCare, Infectious Diseases Clinic
St Louis, Missouri, 63112, United States
Washington U CRS
St Louis, Missouri, United States
SUNY - Buffalo, Erie County Medical Ctr.
Buffalo, New York, 14215, United States
Beth Israel Med. Ctr. (Mt. Sinai)
New York, New York, 10003, United States
NYU Med. Ctr., Dept. of Medicine
New York, New York, 10016, United States
Univ. of Rochester ACTG CRS
Rochester, New York, United States
Unc Aids Crs
Chapel Hill, North Carolina, United States
Carolinas HealthCare System, Carolinas Med. Ctr.
Charlotte, North Carolina, United States
Regional Center for Infectious Disease, Wendover Medical Center CRS
Greensboro, North Carolina, United States
MetroHealth CRS
Cleveland, Ohio, 44109, United States
The Ohio State University Medical Center
Columbus, Ohio, 43210, United States
Hosp. of the Univ. of Pennsylvania CRS
Philadelphia, Pennsylvania, 19104, United States
University of Washington AIDS CRS
Seattle, Washington, 98122, United States
Puerto Rico-AIDS CRS
San Juan, Puerto Rico
Related Publications (6)
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)
BACKGROUNDHill 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)
BACKGROUNDKuritzkes 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)
BACKGROUNDKuritzkes 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. doi: 10.1097/00002030-199904160-00009.
PMID: 10397563BACKGROUNDKuritzkes DR, Bassett RL, Hazelwood JD, Barrett H, Rhodes RA, Young RK, Johnson VA; 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 May 1;36(1):600-3. doi: 10.1097/00126334-200405010-00008.
PMID: 15097303BACKGROUNDFisher M. Nucleoside combinations for antiretroviral therapy: efficacy of stavudine in combination with either didanosine or lamivudine. AIDS. 1998;12 Suppl 3:S9-16.
PMID: 15168718BACKGROUND
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY CHAIR
Kuritzkes D
- STUDY CHAIR
Johnson V