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

NCT ID: NCT00016783

Last Updated: 2013-10-07

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

39 participants

Study Classification

OBSERVATIONAL

Study Completion Date

2006-10-31

Brief Summary

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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

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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.

Conditions

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HIV Infections

Keywords

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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

Study Design

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Study Time Perspective

PROSPECTIVE

Eligibility Criteria

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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
Minimum Eligible Age

2 Years

Maximum Eligible Age

21 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

NIH

Sponsor Role collaborator

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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William Borkowsky, MD

Role: STUDY_CHAIR

New York University Medical Center, Pediatric Infectious Diseases

Locations

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Los Angeles County - USC Med Ctr

Los Angeles, California, United States

Site Status

Children's Hosp of Denver

Denver, Colorado, United States

Site Status

Howard Univ Hosp

Washington D.C., District of Columbia, United States

Site Status

Univ of Miami (Pediatric)

Miami, Florida, United States

Site Status

Chicago Children's Memorial Hosp

Chicago, Illinois, United States

Site Status

Johns Hopkins Hosp - Pediatric

Baltimore, Maryland, United States

Site Status

Children's Hosp of Boston

Boston, Massachusetts, United States

Site Status

Univ of Medicine & Dentistry of New Jersey / Univ Hosp

Newark, New Jersey, United States

Site Status

St. Lukes/Roosevelt Hosp Ctr

New York, New York, United States

Site Status

Columbia Presbyterian Med Ctr

New York, New York, United States

Site Status

Harlem Hosp Ctr

New York, New York, United States

Site Status

University of Rochester Medical Center

Rochester, New York, United States

Site Status

State Univ of New York at Stony Brook

Stony Brook, New York, United States

Site Status

SUNY Health Sciences Ctr at Syracuse / Pediatrics

Syracuse, New York, United States

Site Status

Bronx Lebanon Hosp Ctr

The Bronx, New York, United States

Site Status

Texas Children's Hosp / Baylor Univ

Houston, Texas, United States

Site Status

San Juan City Hosp

San Juan, , Puerto Rico

Site Status

Countries

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United States Puerto Rico

References

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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.

Reference Type BACKGROUND
PMID: 10553903 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 10611346 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 10449278 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 10397562 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 10770542 (View on PubMed)

Other Identifiers

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PACTG P1015

Identifier Type: -

Identifier Source: secondary_id

ACTG P1015

Identifier Type: -

Identifier Source: secondary_id

11650

Identifier Type: REGISTRY

Identifier Source: secondary_id

P1015

Identifier Type: -

Identifier Source: org_study_id