Stopping and Restarting Anti-HIV Drugs in Children and Adolescents With Low Blood Levels of HIV

Intensification of HIV-Specific CD4 and CD8 Activity by Cycling Highly Active Antiretroviral Therapy (HAART) in Pediatric/Adolescent Patients With Less Than 50 HIV RNA Copies/ml

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.

Study Overview

• Status: Completed
• Conditions: HIV Infections

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.

• Study Type: Observational
• Enrollment: 39

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 21 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Note: A Study Monitoring Committee (SMC) recommended on 06/22/05 that this study close, because the primary objectives in this proof-of-concept study could not be achieved. As of 06/28/05, Group A participants will discontinue their drug holiday cycles and will be given the best possible therapy. All participants in this study will have a final study visit to be scheduled as soon as possible, prior to 07/29/05.

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

Study Plan

How is the study designed?

Collaborators and Investigators

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Collaborators: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
• Investigators: Study Chair: William Borkowsky, MD, New York University Medical Center, Pediatric Infectious Diseases

Publications and helpful links

General Publications

• Davey RT Jr, Bhat N, Yoder C, Chun TW, Metcalf JA, Dewar R, Natarajan V, Lempicki RA, Adelsberger JW, Miller KD, Kovacs JA, Polis MA, Walker RE, Falloon J, Masur H, Gee D, Baseler M, Dimitrov DS, Fauci AS, Lane HC. HIV-1 and T cell dynamics after interruption of highly active antiretroviral therapy (HAART) in patients with a history of sustained viral suppression. Proc Natl Acad Sci U S A. 1999 Dec 21;96(26):15109-14. doi: 10.1073/pnas.96.26.15109.
• Garcia F, Plana M, Vidal C, Cruceta A, O'Brien WA, Pantaleo G, Pumarola T, Gallart T, Miro JM, Gatell JM. Dynamics of viral load rebound and immunological changes after stopping effective antiretroviral therapy. AIDS. 1999 Jul 30;13(11):F79-86. doi: 10.1097/00002030-199907300-00002.
• Neumann AU, Tubiana R, Calvez V, Robert C, Li TS, Agut H, Autran B, Katlama C. HIV-1 rebound during interruption of highly active antiretroviral therapy has no deleterious effect on reinitiated treatment. Comet Study Group. AIDS. 1999 Apr 16;13(6):677-83. doi: 10.1097/00002030-199904160-00008.
• Chun TW, Davey RT Jr, Engel D, Lane HC, Fauci AS. Re-emergence of HIV after stopping therapy. Nature. 1999 Oct 28;401(6756):874-5. doi: 10.1038/44755. No abstract available.
• Ruiz L, Martinez-Picado J, Romeu J, Paredes R, Zayat MK, Marfil S, Negredo E, Sirera G, Tural C, Clotet B. Structured treatment interruption in chronically HIV-1 infected patients after long-term viral suppression. AIDS. 2000 Mar 10;14(4):397-403. doi: 10.1097/00002030-200003100-00013.

Study record dates

Study Major Dates

• Study Completion (Actual): October 1, 2006

Study Registration Dates

• First Submitted: June 2, 2001
• First Submitted That Met QC Criteria: August 30, 2001
• First Posted (Estimate): August 31, 2001

Study Record Updates

• Last Update Posted (Estimate): October 7, 2013
• Last Update Submitted That Met QC Criteria: October 4, 2013
• Last Verified: October 1, 2013

More Information

Terms related to this study

• Keywords: Antiretroviral Therapy, Highly Active; Drug Therapy, Combination; Reverse Transcriptase Inhibitors; Anti-HIV Agents; Viral Load; CD8-Positive T-Lymphocytes; Treatment Experienced; CD4 Lymphocyte Count; HIV Protease Inhibitors; Drug Administration Schedule; 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: P1015; PACTG P1015; ACTG P1015; 11650 (Registry Identifier: DAIDS ES)