Some patients taking anti-HIV drugs as part of highly active antiretroviral therapy (HAART) do not show any HIV in the blood; however, some HIV will remain hidden in the body and, if the drugs are stopped, will return to the blood. The purpose of this study is to determine if short periods of stopping HAART increase the activity of CD8 and CD4 cells (cells of the immune system that fight infection), if repeated stopping of these drugs for longer periods of time and restarting them will increase effectiveness of HAART, and if the increased immune system activity as a result of stopping treatment leads to lower levels of HIV over time.

Condition
HIV Infections

Further Study Details: 

Expected Total Enrollment:  39

Some HIV infected patients taking HAART have been able to achieve prolonged suppression of HIV viral load for extended periods of time. However, discontinuing HAART has consistently resulted in HIV's return to plasma. Both CD8 and CD4 cells are markedly reduced in individuals with prolonged HIV suppression; control of and response to cell-associated HIV is dependent on immune-mediated mechanisms involving these cells. It is hypothesized that a brief and low-level increase in HIV levels resulting from HAART interruption might boost HIV-specific CD8 and CD4 T-cell counts. After suppression of viral load with the reintroduction of HAART, the expanded CD8 population might be able to better control viral replication and better respond to cell-associated HIV. Future treatment interruption may lead to longer periods of undetectable viral loads.

Patients are divided into 2 age cohorts, with Cohort 1 consisting of children and adolescents 4 years and older up to 21 years of age, and Cohort 2 consisting of children and adolescents 2 years and older up to 4 years of age. Patients will be assigned to one of 2 groups. Group A patients will participate in drug holiday cycles from HAART and then back to HAART; Group B is a control group that remains on continuous HAART throughout the study. Cycle 1 for Group A patients begins with 18 days of HAART and a 3-day drug holiday. At the end of the drug holiday, viral load is measured and HAART is resumed for 28 days (detectable virus cycle) if viral load is detectable after the drug holiday. If viral load remains below the level of detection, the patient begins the next drug holiday cycle. With each subsequent drug holiday cycle, time off HAART will increase by 2 days. Patients failing 4 repeated detectable virus (28-day treatment) cycles will be taken off study.

Patients will be enrolled in this study for a minimum of 142 weeks. For Group A, HIV viral load and CD4 cell count are measured at the end of each drug holiday and each HAART resumption; HIV-specific CD4 and CD8 responses are measured every 3 cycles; and cell-associated HIV is assessed at entry, at 12-week intervals, and at the end of the study. For Group B, physical exams are conducted and HIV viral load and other blood work are measured every 12 weeks.

Ages Eligible for Study:  2 Years   -   21 Years,  Genders Eligible for Study:  Both

Criteria

Inclusion Criteria

• HIV infected
• For Cohort 1, CD4 T-cell percent greater than 20
• For Cohort 2, CD4 T-cell percent greater than 25
• Viral load less than 400 copies/ml in the year prior to study entry and less than 50 copies/ml at screening
• Taking anti-HIV drugs (including at least 1 protease inhibitor) and have been on anti-HIV drugs for at least 1 year prior to study entry
• Have been on their current drug regimen for at least 4 months
• Willing to follow study procedures
• Parental or guardian consent if under 18 years old
• Acceptable forms of contraception

Exclusion Criteria

• Taking abacavir, nevirapine, efavirenz, or delavirdine
• AIDS-related or other infections needing drug treatment at study entry
• Pregnant or breastfeeding
• Have, or have had in the past, diseases (other than HIV infection) or other conditions that, in the doctor's opinion, would interfere with the study
• Taking experimental drugs without the consent of the protocol team

California
      Los Angeles County - USC Med Ctr, Los Angeles,  California,  90033,  United States
Colorado
      Children's Hosp of Denver, Denver,  Colorado,  802181088,  United States
District of Columbia
      Howard Univ Hosp, Washington,  District of Columbia,  20060,  United States
Florida
      Univ of Miami (Pediatric), Miami,  Florida,  33161,  United States
Illinois
      Chicago Children's Memorial Hosp, Chicago,  Illinois,  606143394,  United States
Maryland
      Johns Hopkins Hosp - Pediatric, Baltimore,  Maryland,  21287,  United States
Massachusetts
      Children's Hosp of Boston, Boston,  Massachusetts,  021155724,  United States
New Jersey
      Univ of Medicine & Dentistry of New Jersey / Univ Hosp, Newark,  New Jersey,  071032714,  United States
New York
      Harlem Hosp Ctr, New York,  New York,  10037,  United States
      Columbia Presbyterian Med Ctr, New York,  New York,  10032,  United States
      SUNY Health Sciences Ctr at Syracuse / Pediatrics, Syracuse,  New York,  13210,  United States
      State Univ of New York at Stony Brook, Stony Brook,  New York,  117948111,  United States
      St. Lukes/Roosevelt Hosp Ctr, New York,  New York,  10025,  United States
      Bronx Lebanon Hosp Ctr, Bronx,  New York,  10457,  United States
      University of Rochester Medical Center, Rochester,  New York,  14642-0001,  United States
Texas
      Texas Children's Hosp / Baylor Univ, Houston,  Texas,  77030,  United States
Puerto Rico
      San Juan City Hosp, San Juan,  009367344,  Puerto Rico

Study chairs or principal investigators

William Borkowsky, MD,  Study Chair,  New York University Medical Center, Pediatric Infectious Diseases   

Study ID Numbers:  ACTG P1015; PACTG P1015
Record last reviewed:  February 2005
Last Updated:  April 7, 2005
Record first received:  June 2, 2001
ClinicalTrials.gov Identifier:  NCT00016783
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08