To elucidate the relationship between virologic risk factors and immunologic and clinical progression in patients receiving monotherapy in protocol ACTG 175, and to compare new treatment regimens with combinations of reverse transcriptase inhibitors in long-term recipients of monotherapy. Specifically, to determine, in patients who have been taking zidovudine (AZT) alone for a long time, whether it is beneficial to add lamivudine (3TC) to AZT or to switch to d4T alone, and also to determine, in patients who have been taking didanosine (ddI) alone for a long time, whether it is beneficial to add AZT or AZT/3TC to ddI. Characteristics of virus replication, pathogenicity, and resistance are thought to determine the durability of virologic and clinical response to nucleoside reverse transcriptase inhibitors. Previous results of ACTG 175 suggest that either a switch to ddI or addition of ddI in patients receiving AZT results in better clinical, virologic, and CD4 cell response compared to continuation of AZT alone.

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

Further Study Details: 

Expected Total Enrollment:  280

Characteristics of virus replication, pathogenicity, and resistance are thought to determine the durability of virologic and clinical response to nucleoside reverse transcriptase inhibitors. Previous results of ACTG 175 suggest that either a switch to ddI or addition of ddI in patients receiving AZT results in better clinical, virologic, and CD4 cell response compared to continuation of AZT alone.

Patients with prior AZT experience only are randomized to receive either d4T alone or AZT/3TC. Patients with prior ddI experience only are randomized to receive ddI/AZT or ddI/AZT/3TC. PER AMENDMENT 8/27/96: The study has been extended 6 months and treatment will be available until March 15, 1997 at the latest. Each patient will have regularly scheduled 12 week safety visits during the extension period. AS PER AMENDMENT 1/22/97: The study has been extended for approximately 16 additional weeks beyond the current 6-month extension. Subjects will be unblinded to their assigned regimen beginning 2/21/97 and will continue therapy for up to 16 weeks in open-label fashion. AS PER AMENDMENT 5/9/97: The study has been extended for an additional 8 weeks; study drug will not be provided after 9/15/97.

Ages Eligible for Study:  12 Years and above,  Genders Eligible for Study:  Both

Criteria

Inclusion Criteria

Concurrent Medication: Recommended:

• PCP prophylaxis in patients with CD4 count <= 200 cells/mm3.

Allowed:

• Chemophylaxis against Mycobacterium tuberculosis.
• Acyclovir.
• Vaccination with pneumococcal vaccine polyvalent.
• Haemophilus B Conjugate vaccine.
• Chemoprophylaxis for MAC and Toxoplasma gondii.
• Antibiotics.
• Recombinant erythropoietin ( EPO ) and G-CSF.
• Systemic corticosteroids for < 21 days.
• Regularly prescribed medications such as antipyretics, analgesics, allergy medications, antidepressants, sleep medications, and oral contraceptives.
• Vitamins and herbal therapies.

Concurrent Treatment: Allowed:

• Limited local radiation therapy to skin.
• Blood transfusions if 3 units or less per 21-day period.
• Acupuncture.
• Visualization techniques.

Patients must have:

• Completed AZT or ddI monotherapy on ACTG 175 and remained on that regimen during any subsequent interval.
• Not reached an ACTG 175 endpoint prior to May 1, 1995.
• Consent of parent or guardian if less than 18 years old.

PER AMENDMENT 8/27/96:

• Patients must be on study/on treatment at the time the protocol study treatment is extended.

Exclusion Criteria

Co-existing Condition: Patients with the following symptoms or conditions are excluded:

• Grade 2 or worse peripheral neuropathy.
• Malignancy requiring systemic therapy.

Concurrent Medication: Excluded:

• Anti-HIV drugs other than study drugs.
• Biologic response modifiers.
• Systemic cytotoxic chemotherapy.
• Any drug known to affect glucuronidation and/or clearance of AZT.

Concurrent Treatment: Excluded:

• Radiation therapy other than limited local therapy to skin.

Patients with the following prior condition are excluded:

• History of acute or chronic pancreatitis.

Prior Medication: Excluded:

• Prior 3TC.
• Acute therapy for an infection (other than HIV) or other medical illness within 14 days prior to study entry.

Current ethanol abuse.

California
      Univ of California / San Diego Treatment Ctr, San Diego,  California,  921036325,  United States
      Stanford Univ Med Ctr, Stanford,  California,  943055107,  United States
      UCLA CARE Ctr, Los Angeles,  California,  90095,  United States
      Univ of Southern California / LA County USC Med Ctr, Los Angeles,  California,  900331079,  United States
      Children's Hosp of Los Angeles, Los Angeles,  California,  90027,  United States
      Harbor UCLA Med Ctr, Torrance,  California,  90502,  United States
      Los Angeles County - USC Med Ctr, Los Angeles,  California,  90033,  United States
Colorado
      Mountain States Reg Hemo Ctr / Univ of Colorado, Denver,  Colorado,  80262,  United States
District of Columbia
      George Washington Univ / Hershey Med Ctr, Washington,  District of Columbia,  20037,  United States
      Georgetown Univ Hosp, Washington,  District of Columbia,  20037,  United States
Georgia
      Emory Hemo Comp Evaluation Clinic / East TN Comp Hemo Ctr, Atlanta,  Georgia,  303652225,  United States
Illinois
      Northwestern Univ Med School, Chicago,  Illinois,  60611,  United States
      Rush Presbyterian - Saint Luke's Med Ctr, Chicago,  Illinois,  60612,  United States
      Cook County Hosp, Chicago,  Illinois,  60612,  United States
Indiana
      Indiana Univ Hosp, Indianapolis,  Indiana,  462025250,  United States
Iowa
      Great Plains - Hemophilia / Univ of Iowa Hosp & Clinic, Iowa City,  Iowa,  52242,  United States
Maryland
      Johns Hopkins Hosp, Baltimore,  Maryland,  21287,  United States
Massachusetts
      Harvard (Massachusetts Gen Hosp), Boston,  Massachusetts,  02114,  United States
      Boston Med Ctr, Boston,  Massachusetts,  02118,  United States
      Worcester Memorial Hosp / Med Ctr of Cntrl MA-Memorial, Worcester,  Massachusetts,  01605,  United States
Michigan
      Michigan State Univ Hemophilia Comprehensive Care Clinic, Lansing,  Michigan,  48912,  United States
Minnesota
      St Paul Ramsey Med Ctr, St. Paul,  Minnesota,  55101,  United States
Missouri
      St Louis Regional Hosp / St Louis Regional Med Ctr, St. Louis,  Missouri,  63112,  United States
New Jersey
      Robert Wood Johnson Med School / Hershey Med Ctr, New Brunswick,  New Jersey,  08903,  United States
New York
      SUNY / State Univ of New York, Syracuse,  New York,  13210,  United States
      Univ of Rochester Medical Center, Rochester,  New York,  14642,  United States
      Bellevue Hosp / New York Univ Med Ctr, New York,  New York,  10016,  United States
      Mount Sinai Med Ctr, New York,  New York,  10029,  United States
      Cornell Univ Med Ctr, New York,  New York,  10021,  United States
      Montefiore Med Ctr / Bronx Municipal Hosp, Bronx,  New York,  10467,  United States
      SUNY / Erie County Med Ctr at Buffalo, Buffalo,  New York,  14215,  United States
      Mount Sinai Med Ctr / Hemophilia Treatment Ctr, New York,  New York,  10029,  United States
North Carolina
      Carolinas Med Ctr, Charlotte,  North Carolina,  28203,  United States
      Univ of North Carolina, Chapel Hill,  North Carolina,  275997215,  United States
      Moses H Cone Memorial Hosp, Greensboro,  North Carolina,  27401,  United States
Ohio
      Univ of Cincinnati, Cincinnati,  Ohio,  452670405,  United States
Pennsylvania
      Univ of Pennsylvania at Philadelphia, Philadelphia,  Pennsylvania,  19104,  United States
      Milton S Hershey Med Ctr, Hershey,  Pennsylvania,  170330850,  United States
South Carolina
      Julio Arroyo, West Columbia,  South Carolina,  29169,  United States
Texas
      Univ Texas Health Science Ctr / Univ Texas Med School, Houston,  Texas,  77030,  United States
Washington
      Univ of Washington, Seattle,  Washington,  981224304,  United States

Study chairs or principal investigators

Katzenstein D,  Study Chair
Hammer S,  Study Chair

Study ID Numbers:  ACTG 302
Record last reviewed:  April 1999
Last Updated:  April 7, 2005
Record first received:  November 2, 1999
ClinicalTrials.gov Identifier:  NCT00000831
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08