Treatment Plan to Decrease Drug Exposure in HIV Infected Adolescents

Structured Treatment Interruption as an Autovaccination Approach to Enhance Immune Based HIV-1 Control in an Adolescent/Young Adult Population

This study will attempt to stimulate the immune system in HIV infected adolescents and young adults so that it can better control the HIV infection. When anti-HIV drugs are stopped for a period of time, the virus "grows back." This may stimulate the immune system, which may then be more effective in controlling the virus.

Study Overview

• Status: Withdrawn
• Conditions: HIV Infections
• Intervention / Treatment: Behavioral: Structured treatment interruption

Detailed Description

The focus of this study is to use Structured Treatment Interruption (STI) as an approach to auto-immunization. The STI management schema is based on current understanding of HIV-1 viral dynamics, pharmacology of available antiretroviral medications, and HIV-specific host responses. This is a Phase II trial to provide preliminary data on the feasibility and possible efficacy of using STI to enhance immune-based control of HIV-1 replication. A steady state HIV-1 viral load determined from historical tests prior to initiating highly active antiretroviral therapy (HAART) will be compared to the steady state viral load post-STI. HIV-1 specific CD4 and CD8 cell responses will be measured before and after the period of STI management and HIV-1 specific CD8 cell maturational phenotype will be assessed and correlated with ability to control viral replication.

Adolescents and young adults who have either had sustained viral suppression on HAART for at least 2 years or who have had sustained viral suppression from 3 to 6 months will be eligible for this study. Participants will have 12 weeks of HAART followed by 2 to 4 weeks of treatment interruption. Participants will undergo three rounds of this regimen. After the third STI, participants will have an additional 12 weeks of HAART and then stop therapy. Participants will be monitored off HAART for up to 20 weeks. During this time, if there is evidence of HIV progression (two consecutive viral loads exceeding 10,000 copies/ml; two consecutive CD4 cell counts under 350 cells/microL; two consecutive CD4 percentages less than 15%; or two consecutive CD4 cell counts less than 50% of baseline), standard continuous antiretroviral therapy will be reinstituted. Plasma HIV RNA will be tested monthly during therapy and weekly while subjects are off treatment. Immunologic studies are monthly throughout the study. Participants will be involved in the study for approximately 2 years.

• Study Type: Interventional
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • San Diego, California, United States
      • University of California at San Diego
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Children's National Medical Center
  • Florida
    • Fort Lauderdale, Florida, United States
      • Children's Diagnostic and Treatment Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States
      • Children's Hospital of Philadelphia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 21 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria

• Acquired HIV infection after age 12 years
• CD4 cell count greater than 500 cells/microL within 30 days of study entry
• Either on HAART for 3 to 6 months with HIV-1 RNA < 400 copies/ml or on HAART for more than 2 years with at least one HIV-1 RNA < 400 copies/ml each six month period
• HAART regimen of two NRTIs and at least one PI (not nelfinavir)
• HIV-1 RNA 5,000 copies/ml prior to HAART and documented CD4 cell values
• CMV positive
• Ability and willingness of subject (and parent/guardian where required) to give informed consent

Exclusion Criteria

• Started initial HAART regimen less than one year after known HIV-1 seroconversion
• Immunosuppressive therapy
• Certain medications
• Pregnancy
• Evidence of an opportunistic infection
• Laboratory values that are classified as Grade 3 or higher toxicities at the time of study enrollment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Collaborators and Investigators

• Sponsor: University of North Carolina, Chapel Hill
• Collaborators: National Institute on Drug Abuse (NIDA); National Institute on Alcohol Abuse and Alcoholism (NIAAA); National Institute of Mental Health (NIMH)
• Investigators: Study Chair: Craig M Wilson, MD, University of Alabama at Birmingham

Publications and helpful links

Helpful Links

• Description of Adolescent Trials Networks (ATN) and contact information

Study record dates

Study Major Dates

• Study Start: July 1, 2003

Study Registration Dates

• First Submitted: August 25, 2003
• First Submitted That Met QC Criteria: August 25, 2003
• First Posted (Estimate): August 26, 2003

Study Record Updates

• Last Update Posted (Actual): March 6, 2017
• Last Update Submitted That Met QC Criteria: March 2, 2017
• Last Verified: July 1, 2016

More Information

Terms related to this study

• Keywords: Treatment experienced; Structured treatment interruption
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; HIV Infections
• Other Study ID Numbers: ATN 008