This study will compare the effectiveness of anti-HIV drug regimens with or without a protease inhibitor (PI) in HIV infected adolescents. It will also determine if monitoring drug levels and adjusting the dose as necessary improves the effectiveness of these regimens.

Condition	Treatment or Intervention	Phase
HIV Infections	Drug: Efavirenz + 2 NRTIs  Drug: Lopinavir/Ritonavir + 2 NRTIs  Procedure: Therapeutic Drug Monitoring	Phase III

HIV infected adolescents may have a significantly higher capacity for immune reconsitution following highly active antiretroviral therapy (HAART). Despite this advantage, HIV infected adolescents are often reluctant to get proper medical care, follow through with doctor appointments, and adhere to medication schedules and regimens necessary to keep the infection under control. Lopinavir/ritonavir, a PI, and efavirenz, a non-nucleoside reverse transcriptase inhibitor (NNRTI), both have long half-lives that make them ideal drugs for the adolescent population, as they are more forgiving if patients miss or sleep through doses. This study will examine the effectiveness of two HAART regimens, one with the protease inhibitor lopinavir/ritonavir and two nucleoside reverse transcriptase inhibitors (NRTIs), and the other with the NNRTI efavirenz and two NRTIs. The efficacy of therapeutic drug monitoring (TDM) and subsequent dose adjustment will also be assessed with both regimens.

Patients will be enrolled in this study for 96 weeks (slightly less than 2 years) and will be randomly assigned into one of two groups. Group 1 will receive lopinavir/ritonavir and 2 NRTIs; Group 2 will receive efavirenz and 2 NRTIs. All patients will be independently and simultaneously randomly assigned to receive either TDM with subsequent dose adjustment if necessary or no TDM or dose adjustment. Patient medical history and physical exam will be conducted at screening, entry, and Weeks 2, 4, 16, 32, 40, 48, 60, 72, 84, and 96. Blood work will be completed at screening, entry, and Weeks 2, 4, 8, 16, 24, 32, 40, 48, 60, 72, 84, and 96. Self-reported pill counts and MEMS TrackCap readings (on lopinavir/ritonavir and efavirenz bottles) will be noted at Weeks 2, 4, 16, 32, 48, 60, 72, 84, and 96. Adherence Questionnaire Modules 1 and 2 will be given to patients at selected visits.

Patients enrolled in PACTG 390 (Different Combination Regimens and Treatment-Switching Guidelines in HIV Infected Children 18 Years of Age and Younger) are encouraged to co-enroll simultaneously in this study and in PACTG 219C (Long-Term Effects of HIV Exposure and Infection in Children).

Ages Eligible for Study:  13 Years   -   23 Years,  Genders Eligible for Study:  Both

Criteria

Inclusion Criteria:

• HIV infected
• HIV RNA 10,000 copies/ml or more at screening
• Weigh 35 kg (77.2 lbs) or more
• ART naive or received a single regimen of combination therapy consisting of NRTIs with or without a single PI (except lopinavir). Zidovudine monotherapy during pregnancy or use of low-dose ritonavir as a PI boost are not excluded.
• For PI experienced patients, have sensitivity to lopinavir at screening
• Able to receive, as part of background ART chosen by their physician, at least one new NRTI that is likely to be active against the patient's virus and unlikely to have cross-resistance with previously used NRTIs
• Not pregnant at screening
• Willing to use acceptable forms of contraception
• Parent, legal guardian, or patient informed consent, where applicable

Exclusion Criteria:

• Prior receipt of any NNRTI or lopinavir
• Use of certain medications
• Grade 3 or 4 clinical or laboratory toxicity as defined by the Division of AIDS Toxicity Table for Grading Severity of Pediatric Adverse Effects
• Chemotherapy for active malignancy
• Acute opportunistic or serious bacterial infection requiring therapy at study entry
• Investigational treatment within 30 days of study entry
• Score of 20 or more on Beck Depression Inventory (BDI-II) or suicidal thoughts on BDI-II (score of 2 or 3 on Question 9), regardless of total score
• Pregnant or breastfeeding

California
      Childrens Hospital Los Angeles, Los Angeles,  California,  90027,  United States; Not yet recruiting
      Los Angeles County Medical Center/USC, Los Angeles,  California,  90033,  United States; Recruiting
      Harbor-UCLA Medical Center, Torrance,  California,  90509,  United States; Recruiting
Colorado
      Childrens Hospital (U. Colorado, Denver), Denver,  Colorado,  80218-1088,  United States; Recruiting
District of Columbia
      Howard University Hospital, Washington,  District of Columbia,  20060,  United States; Not yet recruiting
Florida
      University of South Florida, St. Petersburg,  Florida,  33701,  United States; Recruiting
      University of Florida - Health Science Center, Jacksonville,  Florida,  32209,  United States; Recruiting
      University of Miami (Pediatric), Miami,  Florida,  33136,  United States; Recruiting
Illinois
      Cook County Hospital, Chicago,  Illinois,  60612,  United States; Not yet recruiting
      Chicago Childrens Memorial Hospital (Pediatric), Chicago,  Illinois,  60614,  United States; Not yet recruiting
      The University of Chicago Childrens Hospital, Chicago,  Illinois,  60612,  United States; Recruiting
Louisiana
      Tulane University, Charity Hospital of New Orleans, New Orleans,  Louisiana,  70112-2699,  United States; Recruiting
Massachusetts
      Childrens Hospital of Boston, Boston,  Massachusetts,  02115,  United States; Recruiting
      University of Massachusetts Medical School, Worcester,  Massachusetts,  01655-0001,  United States; Recruiting
Michigan
      Childrens Hospital of Michigan, Detroit,  Michigan,  48201,  United States; Recruiting
Missouri
      St. Louis Children's Hospital, St. Louis,  Missouri,  63110,  United States; Not yet recruiting
New Jersey
      Univ. of Med. & Dentistry of NJ/Univ. Hospital, Newark,  New Jersey,  07101-1709,  United States; Recruiting
New York
      State University of New York at Stony Brook, Stony Brook,  New York,  11794-8111,  United States; Not yet recruiting
      Mt. Sinai Medical Center, New York,  New York,  10029,  United States; Not yet recruiting
      Bronx Lebanon Hospital Center, Bronx,  New York,  10457,  United States; Recruiting
North Carolina
      Duke University (Pediatric), Durham,  North Carolina,  27705,  United States; Recruiting
Tennessee
      St. Jude Children's Research Hopital, Memphis, Memphis,  Tennessee,  38105-2794,  United States; Not yet recruiting
Puerto Rico
      Univ. of Puerto Rico, U. Childrens Hospital AIDS, San Juan,  00936-5067,  Puerto Rico; Not yet recruiting
      San Juan City Hospital, San Juan,  Puerto Rico; Recruiting

Study chairs or principal investigators

Margarita Silio, MD,  Study Chair,  Tulane Medical Center   
Russell Van Dyke, MD,  Study Chair,  Tulane Medical Center   

Study ID Numbers:  PACTG P1034
Record last reviewed:  November 2004
Record first received:  January 9, 2004
ClinicalTrials.gov Identifier:  NCT00075907
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2004-11-08