Stopping and Restarting Anti-HIV Drugs in Children and Adolescents With Low Blood Levels of HIV
Condition: HIV Infections
MeSH terms: HIV Infections
Study type: Observational

Summary: 
      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.
    

Detailed description: 
      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.
    

Time perspective: Prospective
Keywords: Drug Therapy, Combination; Drug Administration Schedule; HIV Protease Inhibitors; CD4 Lymphocyte Count; CD8-Positive T-Lymphocytes; Reverse Transcriptase Inhibitors; Anti-HIV Agents; Viral Load; Antiretroviral Therapy, Highly Active; Treatment Experienced; Treatment Interruption