To compare the proportion of patients who sustain suppression of plasma HIV RNA to undetectable levels [AS PER AMENDMENT 09/19/97: below 200 copies/mL by Roche UltraSensitive assay] among the 3 regimens during the maintenance phase. The objective of antiretroviral therapy is to reduce HIV replication, preserve immunologic function and delay the development of HIV-related complications. In patients administered potent antiretroviral regimens, HIV RNA levels are reduced below 500 copies/ml of plasma and below the level of detection of commercially available assays. This protocol attempts to learn if a less intensive regimen can successfully sustain viral suppression after induction with a triple-drug regimen. The study also addresses whether HIV can be eradicated in patients following prolonged treatment with induction and maintenance regimens.

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

Further Study Details: 

Expected Total Enrollment:  500

The objective of antiretroviral therapy is to reduce HIV replication, preserve immunologic function and delay the development of HIV-related complications. In patients administered potent antiretroviral regimens, HIV RNA levels are reduced below 500 copies/ml of plasma and below the level of detection of commercially available assays. This protocol attempts to learn if a less intensive regimen can successfully sustain viral suppression after induction with a triple-drug regimen. The study also addresses whether HIV can be eradicated in patients following prolonged treatment with induction and maintenance regimens.

All patients will receive open label induction therapy with zidovudine (ZDV), lamivudine (3TC) and indinavir (IDV) for 6 months. Following the 6 month induction phase, patients with undetectable plasma HIV RNA at weeks 16, 20 and 24 will enter the maintenance phase [blinded maintenance phase AS PER AMENDMENT 09/19/97] and be randomized to one of three maintenance regimens, i.e., either continued ZDV/3TC/IDV (control), or ZDV/3TC/IDV placebo or ZDV placebo/3TC placebo/IDV. Prior to randomization, patients are stratified according to entry HIV RNA level (greater than or equal to 30,000 or less than 30,000 copies/ml) and by prior ZDV therapy (at least 7 days or less than 7 days). After 12 months [AS PER AMENDMENT 09/19/97: 18 months] of maintenance therapy, treatment will be withdrawn at 6-month intervals in randomly-selected patients who have achieved undetectable HIV RNA. AS PER 09/19/97 AMENDMENT: After 18 months of blinded maintenance therapy, treatment is unblinded for patients whose HIV RNA levels remain detectable. Such patients receive optimal therapy, either continuing the protocol regimen or initiating alternative therapy. AS PER AMENDMENT 2/27/98: An interim review conducted in January, 1998 demonstrated that the strategy of less intensive antiviral therapy after 6 months of IDV/3TC/ZDV induction therapy is less effective than continuation of triple drug therapy except for ZDV-naive patients assigned to ZDV/3TC. Therefore, the maintenance phase of this study has been discontinued. Patients currently on blinded maintenance are unblinded immediately and have the option of reinitiating open-label triple therapy with IDV/3TC/ZDV or discontinuing study treatment. Patients currently on induction may register for continued open-label triple therapy or may discontinue study treatment. This amendment allows treatment extension so that subjects may receive open-label triple therapy until May 31, 1998. At that time, a rollover protocol or another modification with a longer period of drug supply may become available. Patients who choose to go off treatment are followed until May 31, 1998. AS PER AMENDMENT 04/23/98: This study will now provide treatment with open-label ZDV/3TC/IDV until August 1, 1998. A rollover protocol or another 343 protocol modification with a longer period of drug supply may become available, but this cannot be guaranteed. AS PER AMENDMENT 06/19/98: This study will now provide treatment with open-label ZDV/3TC/IDV until either November 1, 1998 or until 3 months after the rollover study (A5025) is available to the study sites (whichever comes first).

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

Inclusion Criteria

Patients must have:

• Documented HIV infection.
• A CD4 cell count >= 200 cells/mm3 within 90 days prior to study entry.
• Plasma HIV RNA >= 1000 copies/ml within 90 days prior to study entry.

Exclusion Criteria

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

• A malignancy that requires systemic chemotherapy.

Concurrent Medication: Excluded:

• Oral ketoconazole (Nizoral), terfenadine (Seldane), astemizole (Hismanal), cisapride (Propulsid), triazolam (Halcion) or midazolam (Versed).
• All antiretroviral therapies other than study medications.
• Rifabutin and rifampin.
• Investigational drugs and vaccines.
• Systemic cytotoxic chemotherapy.
• Interferon, interleukins, GM-CSF and HIV vaccines.

Patients with any of the following prior conditions are excluded:

• Unexplained temperature > 38.5 degrees C for any 7 days within 30 days prior to study entry.
• Chronic diarrhea as defined as > 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, even if AST and ALT are <= 5.0 X ULN (upper limit of normal).
• A history of >= Grade 2 bilateral peripheral neuropathy within 60 days prior to study entry.
• A history of intolerance to 300 mg/day of ZDV defined as any toxicity requiring a dose reduction or termination of ZDV.

Prior Medication: Excluded:

• Acute therapy for an infection or other medical illness within 14 days prior to study entry.
• Any prior therapy with 3TC or experimental drug 1592.
• More than 2 weeks of lifetime exposure to protease inhibitor therapy; any exposure within 14 days prior to study entry.
• Interferons, interleukins, GM-CSF or HIV vaccines within 30 days prior to study entry.
• Any experimental therapy (drugs or vaccines) within 30 days prior to study entry.
• Rifampin or rifabutin within 14 days prior to study entry.
• Systemic cytotoxic chemotherapy within 30 days prior to study entry.
• Oral ketoconazole (Nizoral), terfenadine (Seldane), astemizole (Hismanal), cisapride (Propulsid), triazolam (Halcion) or midazolam (Versed).

California
      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
      San Francisco Gen Hosp, San Francisco,  California,  941102859,  United States
      Stanford Univ Med Ctr, Stanford,  California,  943055107,  United States
      Univ of Southern California / LA County USC Med Ctr, Los Angeles,  California,  900331079,  United States
      Harbor UCLA Med Ctr, Torrance,  California,  90502,  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
Colorado
      Univ of Colorado Health Sciences Ctr, Denver,  Colorado,  80262,  United States
Florida
      Univ of Miami School of Medicine, Miami,  Florida,  331361013,  United States
Georgia
      Emory Univ, Atlanta,  Georgia,  30308,  United States
Hawaii
      Queens Med Ctr, Honolulu,  Hawaii,  96816,  United States
      Univ of Hawaii, Honolulu,  Hawaii,  96816,  United States
Illinois
      Northwestern Univ Med School, Chicago,  Illinois,  60611,  United States
      Cook County Hosp, Chicago,  Illinois,  60612,  United States
Indiana
      Indiana Univ Hosp, Indianapolis,  Indiana,  462025250,  United States
      Division of Inf Diseases/ Indiana Univ Hosp, Indianapolis,  Indiana,  46202,  United States
Iowa
      Univ of Iowa Hosp and Clinic, Iowa City,  Iowa,  52242,  United States
Louisiana
      Tulane Univ School of Medicine, New Orleans,  Louisiana,  70112,  United States
      Tulane Med Ctr Hosp, New Orleans,  Louisiana,  70112,  United States
Maryland
      Johns Hopkins Hosp, Baltimore,  Maryland,  21287,  United States
      State of MD Div of Corrections / Johns Hopkins Univ Hosp, Baltimore,  Maryland,  212052196,  United States
Massachusetts
      Harvard (Massachusetts Gen Hosp), Boston,  Massachusetts,  02114,  United States
      Beth Israel Deaconess - West Campus, Boston,  Massachusetts,  02215,  United States
Minnesota
      Univ of Minnesota, Minneapolis,  Minnesota,  55455,  United States
      St Paul Ramsey Med Ctr, St. Paul,  Minnesota,  55101,  United States
      Hennepin County Med Clinic, Minneapolis,  Minnesota,  55415,  United States
Missouri
      St Louis Regional Hosp / St Louis Regional Med Ctr, St. Louis,  Missouri,  63112,  United States
Nebraska
      Univ of Nebraska Med Ctr, Omaha,  Nebraska,  681985130,  United States
New York
      Univ of Rochester Medical Center, Rochester,  New York,  14642,  United States
      Mem Sloan - Kettering Cancer Ctr, New York,  New York,  10021,  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
      Beth Israel Med Ctr, New York,  New York,  10003,  United States
      Saint Clare's Hosp and Health Ctr, New York,  New York,  10019,  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
      Case Western Reserve Univ, Cleveland,  Ohio,  44106,  United States
      Univ of Cincinnati, Cincinnati,  Ohio,  452670405,  United States
      Ohio State Univ Hosp Clinic, Columbus,  Ohio,  432101228,  United States
      MetroHealth Med Ctr, Cleveland,  Ohio,  441091998,  United States
South Carolina
      Julio Arroyo, West Columbia,  South Carolina,  29169,  United States
Texas
      Univ of Texas Galveston, Galveston,  Texas,  775550435,  United States
Washington
      Univ of Washington, Seattle,  Washington,  981224304,  United States

Study chairs or principal investigators

Havlir D,  Study Chair
Richman D,  Study Chair

Study ID Numbers:  ACTG 343
Record last reviewed:  April 1997
Last Updated:  April 7, 2005
Record first received:  November 2, 1999
ClinicalTrials.gov Identifier:  NCT00001084
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08