ACTG 388 was a clinical trial that compared three- and four-drug anti-HIV drug regimens and demonstrated the effectiveness of a three-drug regimen. This study will compare the ability of two different three-drug anti-HIV drug regimens to reduce levels of HIV in the blood. The study will also evaluate whether patients discontinue the regimens because of drug side effects.

Condition	Treatment or Intervention
HIV Infections	Drug: lopinavir/ritonavir  Drug: lamivudine/zidovudine  Drug: efavirenz  Drug: lamivudine  Drug: stavudine  Drug: zidovudine  Drug: didanosine

Further Study Details: 

Expected Total Enrollment:  240

ACTG 388 was designed to evaluate two four-drug regimens compared with a three-drug regimen in patients who were relatively treatment naive. Based on the increased complexity and toxicity of four-drug regimens and the resultant negative impact on response as compared with three-drug regimens, studies evaluating simplified potent regimens appear warranted. This study will evaluate simpilified drug regimens designed to enhance virologic activity without necessarily increasing the number of antiretroviral drugs. The study regimens will be assessed for both virologic control and tolerability. The study population will include patients previously enrolled in ACTG 388 and patients with prior advanced HIV disease who received and responded to potent antiretroviral therapy without evidence of virologic relapse.

Patients will be stratified according to ACTG 388 treatment or non-ACTG 388 study participation. Patients will then be randomized to receive either a protease inhibitor (PI)-sparing regimen of 2 nucleoside reverse transcriptase inhibitors (NRTIs) with efavirenz (EFV) (Arm I) or an NRTI-sparing regimen of EFV with lopinavir/ritonavir (LPV/r) (Arm II). Arm I options are enteric-coated didanosine (ddI-EC) plus lamivudine (3TC), ddI-EC plus zidovudine (ZDV), ZDV plus 3TC (or Combivir), stavudine (d4T) plus 3TC, or ddI-EC plus d4T (with exceptions as noted in the protocol). Only LPV/r, EFV, d4T, and ddI are provided by the study; other medications are obtained by nonstudy prescription.

All patients are evaluated for safety and for virologic and immunologic responses at Weeks 4 and 8, then every 8 weeks until the study ends. In addition, all patients have assessments for fat redistribution, fasting lipid profiles, fasting insulin levels, venous lactate levels, and treatment adherence. Patients will be followed for 1.5 to 3 years. Interim safety analyses will be conducted in June 2002 and June 2003. Patients in this study may also enroll in A5125s, a fat distribution and bone mineral density substudy.

Ages Eligible for Study:  13 Years and above,  Genders Eligible for Study:  Both

Criteria

Inclusion Criteria for ACTG 388 Participants

• HIV-1 RNA level <= 200 copies/ml within 70 days of study entry
• Stable anti-HIV drug plan without harmful drug side effects or serious illness at the time of study entry

Inclusion Criteria for Non-ACTG 388 Participants

• Potent anti-HIV drug regimen as a first HIV treatment for at least 18 months
• HIV-1 RNA level >= 80,000 copies/ml or CD4+ count <= 200 cells/mm3 prior to starting anti-HIV drug regimen
• HIV-1 RNA level <= 400 copies/ml (or less than 500 copies/ml by bDNA) within 32 weeks of initial therapy
• HIV-1 RNA level <= 200 copies/ml within 60 days of study entry

Inclusion Criteria for Both ACTG 388 and Non-ACTG 388 Participants

• Acceptable methods of contraception
• Consent of parent or legal guardian if under 18 years of age

Exclusion Criteria for ACTG 388 Participants

• Viral resistance to study drugs as determined by resistance studies during ACTG 388

Exclusion Criteria for ACTG 388 and Non-ACTG 388 Participants

• Pregnancy or breastfeeding
• Certain heart medicines (flecainide or propafenone); antihistamines (astemizole and terfenadine); rifampin; ergot derivatives (dihydroergotamine, ergonovine, ergotamine, or methylergonovine); intestinal agents (cisapride); herbal products (St. John's wort); lovastatin or simvastatin; neuroleptics (pimozide); and sedatives/hypnotics (midazolam or triazolam)
• Allergy study drugs

California
      Univ of Southern California / LA County USC Med Ctr, Los Angeles,  California,  900331079,  United States
Colorado
      Univ of Colorado Health Sciences Ctr, Denver,  Colorado,  80262,  United States
      Denver Dept of Health and Hosps, Denver,  Colorado,  80262,  United States
Connecticut
      Connecticut Children's Medical Center (Pediatric), Farmington,  Connecticut,  06030-3805,  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
      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
Louisiana
      Charity Hosp / Tulane Univ Med School, New Orleans,  Louisiana,  70112,  United States
Minnesota
      Univ of Minnesota, Minneapolis,  Minnesota,  55455,  United States
Missouri
      Washington Univ School of Medicine, St. Louis,  Missouri,  63108,  United States
      Washington Univ / St Louis Connect Care, Saint Louis,  Missouri,  63108,  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
      Cornell Clinical Trials Unit - Chelsea Clinic, New York,  New York,  10011,  United States
North Carolina
      Univ of North Carolina, Chapel Hill,  North Carolina,  275997215,  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 Pennsylvania, Philadelphia,  Pennsylvania,  19104,  United States
Washington
      Univ of Washington, Seattle,  Washington,  98104,  United States
Italy
      Spedali Civili - Carosi, Brescia,  Italy
      Universita di Genova, Genova,  Italy
      Universita degli Studi di Modena e Reggio Emilia, Modena,  Italy
      Ospedale Luigi Sacco Milazzo, Milano,  Italy
Puerto Rico
      Univ of Puerto Rico, San Juan,  009365067,  Puerto Rico

Study chairs or principal investigators

Margaret Fischl, MD,  Study Chair,  University of Miami   

Study ID Numbers:  ACTG A5116; AACTG 5116; Substudy AACTG A5124s; Substudy AACTG A5125s
Record last reviewed:  February 2005
Last Updated:  April 7, 2005
Record first received:  April 14, 2001
ClinicalTrials.gov Identifier:  NCT00014937
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08