Virologic and Immunologic Activity of Continued Lamivudine (3TC) vs Delavirdine (DLV) in Combination With Indinavir (IDV) and Zidovudine (ZDV) or Stavudine (d4T) in 3TC-Experienced Subjects
2 other identifiers
interventional
300
2 countries
31
Brief Summary
To compare the proportion of patients in the 2 zidovudine (ZDV)-containing arms who have a plasma HIV RNA concentration below the limit of detection (defined as 500 copies/ml or less) at Weeks 20 and 24 \[AS PER AMENDMENT 8/24/98: HIV RNA concentration below the limit of detection is now defined as 200 copies/ml or less\]. To compare the safety and tolerability of the different treatment regimens. To compare the decrease in plasma HIV-1 RNA and the change in CD4 count from baseline to the average of Weeks 20 and 24 \[AS PER AMENDMENT 12/19/97: and to the average of Weeks 44 and 48; AS PER AMENDMENT 8/24/98: and the average of Weeks 88 and 96\] in the 2 ZDV-containing arms. To study the emergence of resistance to ZDV, lamivudine (3TC), stavudine (d4T), delavirdine (DLV), and indinavir (IDV) in treated patients. To correlate the antiviral and immunologic activity and emergence of drug resistance with pharmacologic parameters of study drugs. To delineate the pharmacokinetic interactions of IDV and DLV. \[AS PER AMENDMENT 12/19/97: To delineate the possible development of cellular resistance to nucleoside analogs and the consequences of switching nucleoside study drugs on intracellular phosphorylation.\] To document rates and patterns of adherence over the course of the study, from day of randomization through 48 weeks. \[AS PER AMENDMENT 8/24/98: To define long-term durability of the virologic activity of the different treatment regimens, as defined by the proportion of patients with plasma HIV-1 RNA levels that remains below the limit of detection. To define long-term tolerability of the different treatment regimens.\] Although a change in reverse transcriptase (RT) inhibitors is recommended when adding or changing protease inhibitors in a treatment regimen, the choice of available RT inhibitors is often limited by prior exposure, toxicity, or pharmacologic interaction with the protease inhibitors. This study addresses the question of whether to continue 3TC or substitute the nonnucleoside reverse transcriptase inhibitor (NNRTI) DLV when adding IDV to therapy for patients previously treated with ddI or d4T plus 3TC who have greater than 500 copies/ml of plasma HIV-1 RNA. Although the activity of DLV as monotherapy or in combination with nucleoside reverse transcriptase inhibitors is of limited duration due to rapid emergence of resistance, it is possible that DLV will contribute significantly to the activity of 3-drug regimens that include a new RT inhibitor plus a protease inhibitor.
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
31 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
Primary Completion
Last participant's last visit for primary outcome
May 1, 1999
CompletedFirst Submitted
Initial submission to the registry
November 2, 1999
CompletedFirst Posted
Study publicly available on registry
August 31, 2001
CompletedJuly 29, 2013
July 1, 2013
November 2, 1999
July 26, 2013
Conditions
Keywords
Interventions
Eligibility Criteria
You may qualify if:
- Concurrent Medication:
- Required:
- Patients completing ACTG 306 who remain on blinded therapy through the extension period or
- Patients on stable (6 months or greater) ddI/3TC or d4T/3TC combination therapy who have plasma HIV-1 levels higher than 500 copies/ml by the Amplicor HIV-1 Monitor Assay.
- Allowed following contact with Protocol Pharmacologist:
- Diltiazem, nifedipine, phenytoin, and warfarin.
- Patients must have:
- Absolute CD4 count of 200 cells/mm3 or greater.
- HIV-1 RNA levels greater than 500 copies/ml by the Amplicor HIV-1 Monitor assay. NOTE:
- This is a requirement for those receiving study medication. \[AS PER AMENDMENT 12/19/97:
- HIV-1 infection must be documented by any licensed ELISA test kit and confirmed by either Western blot, HIV culture, HIV antigen, plasma HIV RNA, or a second antibody test by a method other than ELISA at any time prior to entry.\]
- Signed, informed consent from a parent or legal guardian for patients under 18 years of age.
- Life expectancy of at least 24 weeks.
You may not qualify if:
- Co-existing Condition:
- Patients with the following symptoms or conditions are excluded:
- Unexplained temperature of 38.5 C or higher for 7 consecutive days, or chronic diarrhea defined as more than 3 liquid stools per day persisting for 15 days, within 30 days prior to study entry.
- Proven or suspected acute hepatitis within 30 days prior to study entry.
- Malignancy that requires systemic chemotherapy. NOTE:Patients with minimal Kaposi's sarcoma (KS) fewer than 5 cutaneous lesions and no visceral disease or tumor-associated edema) are allowed to enroll provided that they do not require systemic therapy.
- Concurrent Medication:
- Excluded:
- Concurrent ZDV (for patients other than those rolling over from ACTG 306).
- Any experimental antiretroviral agents or other experimental therapies.
- Acute therapy for an infection or other medical illnesses within 14 days prior to study entry.
- Recombinant erythropoietin (rEPO), G-CSF, or GM-CSF within 30 days prior to study entry.
- Interferons, interleukins, or HIV vaccines within 30 days prior to study entry.
- Rifampin, rifabutin, cisapride, triazolam, midazolam, terfenadine, astemizole, or loratadine, within 14 days prior to study entry.
- Patients with the following prior conditions are excluded:
- History of acute or chronic pancreatitis.
- +6 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (31)
Univ of Alabama at Birmingham
Birmingham, Alabama, 35294, United States
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
Santa Clara Valley Med Ctr / AIDS Community Rsch Consortium
San Jose, California, 951282699, United States
San Mateo AIDS Program / Stanford Univ
Stanford, California, 943055107, United States
Stanford Univ Med Ctr
Stanford, California, 943055107, 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
Northwestern Univ Med School
Chicago, Illinois, 60611, United States
Cook County Hosp
Chicago, Illinois, 60612, United States
Rush Presbyterian - Saint Luke's Med Ctr
Chicago, Illinois, 60612, United States
Louis A Weiss Memorial Hosp
Chicago, Illinois, 60640, United States
Indiana Univ Hosp
Indianapolis, Indiana, 462025250, United States
State of MD Div of Corrections / Johns Hopkins Univ Hosp
Baltimore, Maryland, 212052196, United States
Johns Hopkins Hosp
Baltimore, Maryland, 21287, 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
SUNY / Erie County Med Ctr at Buffalo
Buffalo, New York, 14215, United States
Beth Israel Med Ctr
New York, New York, 10003, United States
Univ of Rochester Medical Center
Rochester, New York, 14642, United States
Univ of North Carolina
Chapel Hill, North Carolina, 275997215, United States
Carolinas Med Ctr
Charlotte, North Carolina, 28203, United States
Moses H Cone Memorial Hosp
Greensboro, North Carolina, 27401, United States
MetroHealth Med Ctr
Cleveland, Ohio, 441091998, United States
Ohio State Univ Hosp Clinic
Columbus, Ohio, 432101228, United States
Univ of Pennsylvania at Philadelphia
Philadelphia, Pennsylvania, 19104, United States
Julio Arroyo
West Columbia, South Carolina, 29169, United States
Univ of Washington
Seattle, Washington, 981224304, United States
Univ of Puerto Rico
San Juan, 009365067, Puerto Rico
Related Publications (4)
Kuritzkes DR, Marschner IC, Johnson VA, Bassett RL, Eron JJ, Bell DL, Wood K, Sommadossi JP, Morse G, Pettinelli CB. Continued lamivudine (3TC) vs delavirdine (DLV) in combination with indinavir (IDV) and zidovudine (ZDV) or stavudine (d4T) in 3TC-experienced patients. Conf Retroviruses Opportunistic Infect. 1999 Jan 31-Feb 4;6th:159 (abstract no 488)
BACKGROUNDKuritzkes DR, Bassett RL, Johnson VA, Marschner IC, Eron JJ, Sommadossi JP, Acosta EP, Murphy RL, Fife K, Wood K, Bell D, Martinez A, Pettinelli CB. Continued lamivudine versus delavirdine in combination with indinavir and zidovudine or stavudine in lamivudine-experienced patients: results of Adult AIDS Clinical Trials Group protocol 370. AIDS. 2000 Jul 28;14(11):1553-61. doi: 10.1097/00002030-200007280-00011.
PMID: 10983642BACKGROUNDIckovics JR, Cameron A, Zackin R, Bassett R, Chesney M, Johnson VA, Kuritzkes DR; Adult AIDS Clinical Trials Group 370 Protocol Team. Consequences and determinants of adherence to antiretroviral medication: results from Adult AIDS Clinical Trials Group protocol 370. Antivir Ther. 2002 Sep;7(3):185-93. doi: 10.1177/135965350200700308.
PMID: 12487386BACKGROUNDKuritzkes 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: 15097303BACKGROUND
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY CHAIR
Kuritzkes D
- STUDY CHAIR
Johnson V