Little is known about what treatment combinations are best for HIV infected children. This study will examine the long-term effectiveness of different anti-HIV drug combinations in children and strategies for switching treatment if the first treatment does not work. The study will enroll children who have not previously taken anti-HIV medication.

Some children may also enroll in a substudy that will observe changes in body fat in children taking anti-HIV medications.

Condition	Treatment or Intervention	Phase
HIV Infections	Drug: Highly active antiretroviral therapy	Phase II Phase III

Further Study Details: 

Expected Total Enrollment:  256

Antiretroviral therapy in children aims to prolong clinical and immunologic health. Currently, there are no data defining a particular highly active antiretroviral therapy (HAART) strategy as the optimal first-line therapy for children. This study will evaluate the long-term efficacy of two HAART regimens used as initial therapy: 1) two nucleoside reverse transcriptase inhibitors (NRTIs) plus a protease inhibitor (PI), and 2) two NRTIs plus a nonnucleoside reverse transcriptase inhibitor (NNRTI). It will also evaluate different strategies for switching therapy when the initial regimen fails. The long-term nature of this study should clarify whether early switching of therapy improves immunologic and virologic outcomes, or results in a more rapid exhaustion of treatment options. The study will be conducted in the United States and in Europe.

Participants in this study will have a CD4 cell count and viral load test during a screening visit. Participants will have an entry visit that will include blood and urine tests, a neurologic exam, a chest X-ray, and a behavioral and learning development exam. Participants will then be randomly assigned to one of four groups: Groups 1A and 1B will receive two NRTIs plus a PI; Groups 2A and 2B will receive two NRTIs plus an NNRTI. The medications allowed in the study are: abacavir succinate, didanosine, lamivudine, lamivudine/zidovudine, stavudine, zalcitabine, and zidovudine (NRTIs); efavirenz and nevirapine (NNRTIs); and amprenavir, indinavir, lopinavir/ritonavir, nelfinavir, saquinavir, and ritonavir (PIs).

For participants whose initial regimen fails, a second-line therapy is strongly encouraged. In this second-line therapy, participants who initially took NRTIs with a PI will switch to NRTIs and an NNRTI. Participants who initially took NRTIs and an NNRTI will switch to NRTIs and a PI. The timing of the switch will be based on the participant’s group: Groups 1A and 2A will switch to second-line treatment when viral load is 1000 copies/ml or greater; Groups 1B and 2B will switch to second-line treatment when viral load is 30,000 copies/ml or greater.

Participants will have study visits at Weeks 2, 4, 8, 12, 16, 24, and every 12 weeks thereafter until the drug regimen is switched to second-line treatment. Participants will then have a re-entry visit and the schedule of visits will restart. Participants will be in the study between 4 and 8 years, depending on when they enroll.

Participants in the European portion of the study may be asked to enroll in a substudy to observe the development and progression of lipodystrophy syndrome.

Ages Eligible for Study:  up to  18 Years,  Genders Eligible for Study:  Both

Criteria

Inclusion Criteria

• Older than 30 days and younger than 18 years of age (may enroll up to the day before their 18th birthday)
• HIV infected
• Not previously on HAART or received anti-HIV drugs for less than 56 consecutive days after birth to prevent mother-to-infant transmission, and/or no more than two doses of nevirapine
• Acceptable methods of contraception

Exclusion Criteria

• Grade 3 or 4 clinical or laboratory toxicity as defined by the study
• Active opportunistic infection and/or a serious bacterial infection at the time of study entry
• Pancreas, nervous system, blood, liver, or kidney problems that make it impossible to take study medications
• Taking any medication that cannot be combined with the study medications
• Received therapy for cancer
• Pregnant or breast-feeding

California
      Children's Hosp of Oakland, Oakland,  California,  94609-1809,  United States; Recruiting
      UCSD Mother, Child & Adolescent HIV Programs, San Diego,  California,  92103,  United States; Recruiting
      Children's Hosp of LA (Pediatric), Los Angeles,  California,  90054,  United States; Recruiting
      Long Beach Memorial (Pediatric), Long Beach,  California,  90801,  United States; Recruiting
      Los Angeles County Medical Center/USC, Los Angeles,  California,  90033,  United States; Recruiting
Connecticut
      Connecticut Childrens Med Ctr (Pediatric), Farmington,  Connecticut,  06030-3805,  United States; Recruiting
District of Columbia
      Howard Univ Hosp, Washington,  District of Columbia,  20060,  United States; Recruiting
Florida
      Univ of Florida, Gainsville, Gainesville,  Florida,  32610-0296,  United States; Recruiting
      Univ of Miami (Pediatric), Miami,  Florida,  33136,  United States; Recruiting
      Univ of South Florida, St. Petersburg,  Florida,  33701,  United States; Recruiting
      North Broward Hosp District, Fort Lauderdale,  Florida,  33316,  United States; Recruiting
Illinois
      Chicago Children's Memorial Hosp, Chicago,  Illinois,  60614-3394,  United States; Recruiting
      Univ of Chicago Childrens Hosp, Chicago,  Illinois,  60637,  United States; Recruiting
Louisiana
      Tulane Univ / Charity Hosp of New Orleans, New Orleans,  Louisiana,  70112-2699,  United States; Recruiting
Massachusetts
      Children's Hospital of Boston, Boston,  Massachusetts,  02115,  United States; Recruiting
      Lawrence Family Health Center, Lawrence,  Massachusetts,  01841-2884,  United States; Not yet recruiting
      Lowell Community Health Center, Lawrence,  Massachusetts,  01841-2884,  United States; Not yet recruiting
      University of Massachusetts Medical School, Worcester,  Massachusetts,  01655-0001,  United States; Recruiting
Missouri
      St. Louis Children's Hospital, St. Louis,  Missouri,  63110,  United States; Recruiting
New Jersey
      Univ of Medicine & Dentistry of New Jersey / Univ Hosp, Newark,  New Jersey,  07103-2714,  United States; Recruiting
      Robert Wood Johnson AIDS Program, New Brunswick,  New Jersey,  08901-1969,  United States; Recruiting
New York
      State Univ of New York at Stony Brook, Stony Brook,  New York,  11794-8111,  United States; Recruiting
      SUNY Health Sciences Ctr at Syracuse / Pediatrics, Syracuse,  New York,  13210,  United States; Recruiting
      The Columbia Presbyterian Med Ctr, New York,  New York,  10032,  United States; Recruiting
      Harlem Hosp, New York,  New York,  10037,  United States; Recruiting
      Univ of Rochester Med Ctr, Rochester,  New York,  14642-0001,  United States; Recruiting
      New York University School of Medicine, New York,  New York,  10016,  United States; Recruiting
North Carolina
      Duke Univ (Pediatric), Durham,  North Carolina,  27705,  United States; Recruiting
      University of North Carolina at Chapel Hill, Chapel Hill,  North Carolina,  27599-7220,  United States; Recruiting
Oregon
      Oregon Health and Science University, Portland,  Oregon,  97239,  United States; Recruiting
Tennessee
      Saint Jude Children's Research Hosp of Memphis, Memphis,  Tennessee,  38105-2794,  United States; Recruiting
      Vanderbilt Univ Med Ctr, Nashville,  Tennessee,  37232,  United States; Recruiting
Texas
      Texas Children's Hosp / Baylor Univ, Houston,  Texas,  77030,  United States; Recruiting
      Baylor (Texas Childrens Hosp)(Pediatric), Houston,  Texas,  77030,  United States; Recruiting
Washington
      Children's Hospital and Regional Medical Center/Se, Seattle,  Washington,  98105-0371,  United States; Recruiting
Bahamas
      Princess Margaret Hospital, Nassau,  N1784,  Bahamas; No longer recruiting
Brazil
      Federal University of Rio de Janiero, Rio de Janeiro,  21941-590,  Brazil; No longer recruiting
      Escola de Medicina, Universidade Federal de Minas, Belo Horizonte,  30130-100,  Brazil; No longer recruiting
Puerto Rico
      San Juan City Hosp, San Juan,  Puerto Rico; Recruiting
      Univ of Puerto Rico, U. Childrens Hosp AIDS, San Juan,  00936-5067,  Puerto Rico; Recruiting

Study chairs or principal investigators

Ross McKinney, MD,  Study Chair,  Duke University   
Ann J. Melvin, MD,  Study Chair,  Children's Hospital and Medical Center, Seattle, WA   

Study ID Numbers:  PENTA 9/PACTG 390; PENPACT-1B
Record last reviewed:  February 2005
Last Updated:  April 7, 2005
Record first received:  June 7, 2002
ClinicalTrials.gov Identifier:  NCT00039741
Health Authority: United States: Food and Drug Administration
ClinicalTrials.gov processed this record on 2005-04-08