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

HIV Infections Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00016783
• Other study ID #: P1015
• Secondary ID: PACTG P1015ACTG
• Status: Completed
• Phase: N/A
• First received: June 2, 2001
• Last updated: October 4, 2013
• Est. completion date: October 2006

Study information

• Verified date: October 2013
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 39
• Est. completion date: October 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 2 Years to 21 Years

Eligibility

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 Design

Time Perspective: Prospective

Related Conditions & MeSH terms

• HIV Infections

Locations

Country	Name	City	State
Puerto Rico	San Juan City Hosp	San Juan
United States	Johns Hopkins Hosp - Pediatric	Baltimore	Maryland
United States	Children's Hosp of Boston	Boston	Massachusetts
United States	Bronx Lebanon Hosp Ctr	Bronx	New York
United States	Chicago Children's Memorial Hosp	Chicago	Illinois
United States	Children's Hosp of Denver	Denver	Colorado
United States	Texas Children's Hosp / Baylor Univ	Houston	Texas
United States	Los Angeles County - USC Med Ctr	Los Angeles	California
United States	Univ of Miami (Pediatric)	Miami	Florida
United States	Columbia Presbyterian Med Ctr	New York	New York
United States	Harlem Hosp Ctr	New York	New York
United States	St. Lukes/Roosevelt Hosp Ctr	New York	New York
United States	Univ of Medicine & Dentistry of New Jersey / Univ Hosp	Newark	New Jersey
United States	University of Rochester Medical Center	Rochester	New York
United States	State Univ of New York at Stony Brook	Stony Brook	New York
United States	SUNY Health Sciences Ctr at Syracuse / Pediatrics	Syracuse	New York
United States	Howard Univ Hosp	Washington	District of Columbia

Sponsors (2)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Countries where clinical trial is conducted

United States,  Puerto Rico, 

References & Publications (5)

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. — View Citation

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. — View Citation

García F, Plana M, Vidal C, Cruceta A, O'Brien WA, Pantaleo G, Pumarola T, Gallart T, Miró JM, Gatell JM. Dynamics of viral load rebound and immunological changes after stopping effective antiretroviral therapy. AIDS. 1999 Jul 30;13(11):F79-86. — View Citation

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. — View Citation

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. — View Citation

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