The purpose of this study is to compare the effectiveness, safety, and tolerability of 3 anti-HIV combination treatments that do not use protease inhibitors (PIs). The current rule for starting treatment of HIV infection is to combine members from different classes of anti-HIV drugs, such as 2 nucleoside reverse transcriptase inhibitors (NRTIs) and either a PI or a nonnucleoside reverse transcriptase inhibitor (NNRTI). However, these combinations can be complicated and difficult to take, can cause a number of side effects, and may become ineffective. Combinations that are simpler, better tolerated, and more effective are needed. Because PIs can cause long-term side effects and because HIV can become resistant to many of them at the same time, anti-HIV combination treatments that do not use PIs are being tested.

Condition	Treatment or Intervention	Phase
HIV Infections	Drug: Abacavir sulfate, Lamivudine and Zidovudine  Drug: Atazanavir  Drug: Lamivudine/Zidovudine  Drug: Abacavir sulfate  Drug: Efavirenz  Drug: Nevirapine  Drug: Lamivudine  Drug: Stavudine  Drug: Zidovudine  Drug: Didanosine	Phase III

Further Study Details: 

Expected Total Enrollment:  1125

Current treatment guidelines recommend combination regimens of 2 nucleoside analogues with either a PI or an NNRTI for the initial treatment of HIV infection. However, the efficacy of current regimens is limited by their complexity, pharmacokinetic characteristics, short- and long-term side effects, and drug-resistance profiles at the time of virologic failure. Consequently, the identification of new initial regimens that are simpler, better tolerated, preserve treatment options in the event of failure, and improve antiretroviral potency is needed. In addition, recent concern over the long-term toxicities of PIs and the extensive cross-resistance among the available PIs have led to the testing of PI-sparing regimens.

Participants will be in this study for a minimum of 120 weeks and a maximum of approximately 4 years. In Step 1, patients are randomly selected to receive 1 of 3 blinded treatment regimens: abacavir (ABC)/lamivudine (3TC)/zidovudine (ZDV)/efavirenz (EFV), ABC/3TC/ZDV, or 3TC/ZDV/EFV. Patients with confirmed virologic failure on Step 1 and two successive plasma HIV RNA levels of 10,000 copies/ml or greater must register to Step 2. Patients with confirmed virologic failure on Step 1 and whose plasma HIV RNA is under 10,000 copies/ml may remain on Step 1 or register to Step 2. [AS PER AMENDMENT 04/11/03: Discontinuation of Arm B was recommended. Consequently, Arms A and C were unblinded to EFV but not to ABC. A number of options are available for patients originally randomized to Arm B.]

Step 2 is open label. Regimens include 2 or 3 nucleoside reverse transcriptase inhibitors (NRTIs) in combination with EFV, atazanavir (ATZ), ritonavir-boosted ATZ, or tenofovir disoproxil fumarate (TDF). Patients on Arm B treatment who have an HIV RNA level less than 200 copies/ml within the past 8 weeks are eligible for randomization to open-label intensification of Arm B on Step 3.

Step 3 regimens include ABC/3TC/ZDV plus either EFV or TDF. Patients with evidence of treatment-limiting toxicity to Step 3 study drugs have the option of substituting d4T for ZDV, ddI for ABC or TDF, and/or NVP for EFV. Patients with confirmed virologic failure on Step 3 and whose plasma HIV RNA is less than 10,000 copies/ml may either remain on Step 3 or register to Step 4. Patients with two successive plasma HIV RNA levels of 10,000 copies/ml or greater on Step 3 must register to Step 4.

Step 4 is open label. Regimens include two or three NRTIs plus EFV, ATV, ritonavir-boosted ATV, or TDF. Clinical assessments and laboratory evaluations are done at entry, at Weeks 2, 4, 6, 8, 12, 16, 20, 24, and then every 8 weeks thereafter for the duration of the study. Evaluations are also required when a protocol-allowed drug substitution is made. In addition, 3 substudies are being conducted: a neurology substudy for efavirenz, a pharmacology substudy for atazanavir, and a viral dynamics substudy.

Ages Eligible for Study:  16 Years and above,  Genders Eligible for Study:  Both

Criteria

Inclusion Criteria

Patients may be eligible for this study if they:

• Are HIV-positive.
• Have a viral load of at least 400 copies/ml within 90 days prior to study entry.
• Are at least 16 years old.
• Weigh at least 40 kg.
• Have a negative pregnancy test within 48 hours before starting study drugs, if female and able to have children.
• Agree to use 2 effective methods of birth control while taking, and for 3 months after stopping, the study medications.
• Provide written consent of a parent or guardian, if under 18 years of age.

Exclusion Criteria

Patients will not be eligible for this study if they:

• Have taken anti-HIV drugs in the past.
• Are allergic to any of the study drugs or ingredients.
• Are pregnant or breast-feeding.
• Have taken any of the following drugs within 14 days prior to study entry: amiodarone, astemizole, bepridil, cisapride, ergot or ergot derivatives, systemic itraconazole, systemic ketoconazole, midazolam, propoxyphene, quinidine, rifampin, terfenadine, thalidomide, triazolam, or St. John's wort.
• Have taken drugs that influence the immune system, HIV or other vaccines, or investigational drugs within 30 days prior to study entry. Prednisone at a dose of 10 mg or less daily is allowed.
• Have taken drugs or been hospitalized for serious infections or medical illnesses within 14 days prior to study entry.
• Have growths or tumors that require drug therapy.
• Have Pneumocystis carinii pneumonia that is not clinically stable and whose treatment is not completed at least 7 days prior to study entry.
• Have infections or medical illnesses that are not under control or that have not received complete treatment before study entry.
• Have any condition that, in the opinion of the investigator, would prevent them from properly participating in the study.
• Abuse drugs or alcohol.
• This study has been updated to exclude patients who are receiving systemic itraconazole and rifabutin.

Alabama
      Univ of Alabama at Birmingham, Birmingham,  Alabama,  35294,  United States
California
      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
      Harbor UCLA Med Ctr, Torrance,  California,  90502,  United States
      San Mateo AIDS Program / Stanford Univ, Stanford,  California,  943055107,  United States
      Willow Clinic, Menlo Park,  California,  94025,  United States
      Univ of California San Francisco, San Francisco,  California,  94110,  United States
      Kaiser Permanente LAMC, Los Angeles,  California,  90027,  United States
      Univ of California, San Diego, San Diego,  California,  92103,  United States
      Univ of California, Davis Med Ctr, Sacramento,  California,  95814,  United States
Colorado
      Univ of Colorado Health Sciences Ctr, Denver,  Colorado,  80262,  United States
District of Columbia
      Georgetown Univ Med Ctr, Washington,  District of Columbia,  20007,  United States
Florida
      Univ of Miami School of Medicine, Miami,  Florida,  331361013,  United States
Georgia
      Emory Univ, Atlanta,  Georgia,  30308,  United States
Hawaii
      Univ of Hawaii, Honolulu,  Hawaii,  96816,  United States
Illinois
      Northwestern Univ Med School, Chicago,  Illinois,  60611,  United States
      Rush Presbyterian - Saint Luke's Med Ctr, Chicago,  Illinois,  60612,  United States
      The CORE Ctr, Chicago,  Illinois,  60612,  United States
Indiana
      Indiana Univ Hosp, Indianapolis,  Indiana,  462025250,  United States
      Methodist Hosp of Indiana / Life Care Clinic, Indianapolis,  Indiana,  46202,  United States
      Wishard Hosp, Indianapolis,  Indiana,  46202,  United States
Iowa
      Univ of Iowa Hosp and 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
      Beth Israel Deaconess - West Campus, Boston,  Massachusetts,  02215,  United States
      Boston Med Ctr, Boston,  Massachusetts,  02118,  United States
Minnesota
      Univ of Minnesota, Minneapolis,  Minnesota,  55455,  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
      Bellevue Hosp / New York Univ Med Ctr, New York,  New York,  10016,  United States
      Cornell Univ Med Ctr, New York,  New York,  10021,  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
      Aaron Diamond AIDS Rsch Ctr / Rockefeller Univ, New York,  New York,  10021,  United States
      Columbia Presbyterian Med Ctr, New York,  New York,  10032,  United States
      St Mary's Hosp (Univ of Rochester/Infectious Diseases), Rochester,  New York,  14642,  United States
      Cornell Clinical Trials Unit - Chelsea Clinic, New York,  New York,  10011,  United States
      Community Health Network Inc, Rochester,  New York,  14642,  United States
North Carolina
      Univ of North Carolina, Chapel Hill,  North Carolina,  275997215,  United States
      Moses H Cone Memorial Hosp, Greensboro,  North Carolina,  27401,  United States
      Duke Univ Med Ctr, Durham,  North Carolina,  27710,  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
Pennsylvania
      Univ of Pittsburgh, Pittsburgh,  Pennsylvania,  15213,  United States
      Univ of Pennsylvania, Philadelphia,  Pennsylvania,  19104,  United States
      Philadelphia Veterans Administration Med Ctr, Philadelphia,  Pennsylvania,  19104,  United States
Rhode Island
      Miriam Hosp / Brown Univ, Providence,  Rhode Island,  02906,  United States
      Brown Univ / Miriam Hosp, Providence,  Rhode Island,  02906,  United States
South Carolina
      Julio Arroyo, West Columbia,  South Carolina,  29169,  United States
Tennessee
      Vanderbilt Univ Med Ctr, Nashville,  Tennessee,  37203,  United States
Texas
      Univ of Texas Galveston, Galveston,  Texas,  775550435,  United States
      Univ of Texas, Southwestern Med Ctr of Dallas, Dallas,  Texas,  75390,  United States
Washington
      Univ of Washington, Seattle,  Washington,  98104,  United States
Puerto Rico
      Univ of Puerto Rico, San Juan,  009365067,  Puerto Rico

Study chairs or principal investigators

Roy Gulick, MD,  Study Chair
Cecilia Shikuma, MD,  Study Chair

Study ID Numbers:  ACTG A5095; AACTG 5095; Substudy ACTG A5097s; Substudy AACTG 5107s; Substudy AACTG 5166s; Substudy ACTG A5166s; Substudy AACTG 5097s; Substudy ACTG A5107s
Record last reviewed:  November 2004
Last Updated:  January 13, 2005
Record first received:  March 16, 2001
ClinicalTrials.gov Identifier:  NCT00013520
Health Authority: United States: Food and Drug Administration
ClinicalTrials.gov processed this record on 2005-04-08