Preservation and Expansion of T-cell Subsets Following HAART De-intensification to Atazanavir/Ritonavir (ATV/r)
1 other identifier
interventional
102
2 countries
23
Brief Summary
This study proposes to evaluate a pre-DHHS guideline of HAART initiation and then de-intensification management strategy in adolescents with mild immunosuppression and compare changes in CD4% from baseline to week 48 and then during de-intensification.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for not_applicable hiv-infections
Started Oct 2007
Longer than P75 for not_applicable hiv-infections
23 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
June 22, 2007
CompletedFirst Posted
Study publicly available on registry
June 26, 2007
CompletedStudy Start
First participant enrolled
October 1, 2007
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 1, 2013
CompletedStudy Completion
Last participant's last visit for all outcomes
June 1, 2013
CompletedResults Posted
Study results publicly available
June 24, 2016
CompletedMarch 29, 2017
May 1, 2016
5.7 years
June 22, 2007
March 18, 2016
February 27, 2017
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Difference in CD4+ T Cell Percentage Between Week 0 and Week 48
Week 0 and Week 48
Difference in CD4+ T Cell Percentage Between Week 48 and Week 152
152 Weeks
Secondary Outcomes (50)
Difference in CD4+ T Cell Count Between Week 0 and Week 48
48 weeks
Difference in CD4+ T Cell Count Between Week 48 and Week 152
152 weeks
Difference in CD4+ Naïve T Cell Count Between Week 0 and Week 48
48 weeks
Difference in CD4+ Naïve T Cell Count Between Week 48 and Week 152
152 weeks
Difference in CD4+ Termed Central Memory (TCM) Count Between Week 0 and Week 48
48 weeks
- +45 more secondary outcomes
Study Arms (2)
Experimental Arm
EXPERIMENTALSubjects in the experimental group will begin HAART consisting of TDF/FTC/ATV/r (preferred), AZT/3TC/ATV/r or other recommended NRTI backbone with ATV/r upon entry or to begin treatment under current DHHS guidelines. Subjects in the experimental group who achieve virologic control by week 24 and maintain good control through 48 weeks will then de-intensify to ATV/r alone and will be followed for an additional two years.
Standard Care Arm
OTHERSubjects randomized to the standard care arm will begin HAART with TDF/FTC/ATV/r (preferred), AZT/3TC/ATV/r, or other recommended ATV/r based HAART regimen according to current DHHS standard of care and will be followed for a total of three years. Under these guidelines and under current clinical standards, subjects on the standard care arm will begin therapy when the CD4+ T cell count drops below 350 cells/mm3 or other clinical criteria necessitating treatment as determined by the site clinician occur.
Interventions
Treatment: TDF/FTC/ATV/r (preferred), AZT/3TC/ATV/r or other recommended NRTI backbone with ATV/r. Duration: Subjects in the experimental group who achieve virologic control by week 24 and maintain good control through 48 weeks will then de-intensify to ATV/r alone and will be followed for an additional two years.
Progression: Subjects on the standard care arm will begin therapy when the CD4+ T cell count drops below 350 cells/mm3 or other clinical criteria necessitating treatment as determined by the site clinician occur. Treatment: HAART with TDF/FTC/ATV/r (preferred), AZT/3TC/ATV/r, or other recommended ATV/r based HAART regimen according to current DHHS standard of care. Duration: three years.
Eligibility Criteria
You may qualify if:
- Age 18 yrs and 0 days to 24 yrs and 364 days;
- CD4+ T cells \> 350/mm3 and HIV RNA ≥ 1,000 copies/ml as determined by two consecutive measures within 6 months of entry with the second measure being collected at pre-entry;
- Infected after age 9. HIV-1 infection should be documented by any licensed ELISA test kit and confirmed by Western blot, HIV-1 culture, HIV-1 antigen, plasma HIV-1 RNA, or a second antibody test by a method other than ELISA at any time prior to entry; Note: Subjects who are in acute seroconversion as evidenced by being ELISA negative (antibody negative) and DNA PCR or HIV-1 RNA positive or who are ELISA positive but Western Blot indeterminate are not eligible.
- Subjects must be naïve to ARV medications except for women who have received HAART for prevention of maternal to child transmission (MTCT) that meet the following criteria: HAART (defined as three medications from two classes) given for no more than six months for prevention of MTCT, Evidence of viral suppression on the HAART regimen defined as a plasma RNA level below the level of detection for the assay used by the site either during the third trimester or around the time of delivery, A minimum of six months since HAART exposure for prevention of MTCT, and Exposure to HAART for a single pregnancy only; Note: Prior treatment with Trizivir for prevention of MCTC is also permitted as long as viral suppression is documented at the time of delivery or in the last trimester, whichever is most recent.
- HIV genotype without major resistance mutations to ATV/r. The following genotypic mutations exclude subjects from participation in ATN 061: Major ATV mutations I50L; I84V; N88D/S, Major PI mutations including: D30N; V32I; L33I/F/V; M46I/L; I47V/A; G48V; I50V/L; I54V/L/A/M/T/S; L76V; V82A/F/T/S/L; L90M, Any major PI mutation as defined by the most current IAS-USA Drug Resistance Mutations Figures that would adversely affect a subject's future PI choices, Major RT mutations: Q151M and 69 insertion complex; Decisions regarding the selection of an NRTI backbone for subjects with NRTI resistance mutations other than those described above will be made by the site PI in consultation with the protocol chair or his designee. Whenever possible and not otherwise contraindicated, NRTI choices should be congruent with the protocol-specified preferred regimens. The site PI must provide a copy of the genotype analysis along with their proposed regimen for review; Note: Subjects who cannot go onto either FTC/TDF or AZT/3TC must have the regimen approved by the protocol team following pre-entry screening and prior to study entry. Note: All HIV-1 genotype profiles with ANY resistance mutations must be evaluated by a physician specializing in the care of HIV-infected patients prior to final determination of subject eligibility. Polymorphism mutations should NOT be reported since their clinical significance is unknown. All other (major and minor) mutations should be appropriately categorized and reported as indicated by the case report form. In circumstances where there are numerous such mutations or other concerns present, consultation with the protocol team by the evaluating physician via the ATN QNS is highly encouraged.
- Calculated creatinine clearance ≥60 mL/min as estimated by the Cockcroft-Gault equation: For men, (140 - age in years) x (body weight in kg) ÷ (serum creatinine in mg/dL x 72) = CrCl (mL/min)\*;\*For women, multiply the result by 0.85 = CrCl (mL/min);
- For females with child-bearing potential, agreement to use one effective birth control method and willing to postpone pregnancy for the duration of the study (See Section 9.3 - criteria for class C drugs should be followed); and
- Able to provide written informed consent/assent.
You may not qualify if:
- Pregnancy;
- On systemic immunosuppressive therapy or immune modulating therapy (short courses (\<14 days) of prednisone for reactive airway disease \[RAD\] are permitted but not within 30 days prior to study entry);
- Currently breast feeding;
- Current treatment for active serious systemic bacterial infections;
- Active hepatitis B infection as defined by Hepatitis B Ag positive;
- Treatment with immune modulators including IL-2, intravenous gammaglobulin, and therapeutic or other experimental vaccines including HIV-1 vaccine given for primary prevention at any time;
- History of cardiac conduction abnormalities including one or more of the following: Symptomatic heart block, Third-degree heart block, even if asymptomatic, Pre-excitation syndromes, Heart Rate \<40 bpm, Ventricular pause length \>3 seconds, QTc \> 500 msec, and Cardiomyopathy;
- Disallowed Medications (see Section 5.3.2);
- Active drug or alcohol use or dependence that, in the opinion of the site personnel, would interfere with adherence to the study;
- History of chronic renal insufficiency or Grade 3 or greater serum creatinine; and
- Any confirmed grade 3 or greater laboratory value at pre-entry (with the exception of grade 3 or greater lipids or platelets).
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (23)
Children's Hopsital of Los Angeles
Los Angeles, California, 90027, United States
University of Southern California - IMPAACT Site
Los Angeles, California, 90033, United States
University of California at San Francisco
San Francisco, California, 94118, United States
Children's Hospital of Denver - IMPAACT Site
Aurora, Colorado, 80045, United States
Children's National Medical Center
Washington D.C., District of Columbia, 20010, United States
Howard University - IMPAACT Site
Washington D.C., District of Columbia, 20060, United States
Children's Diagnostic and Treatment Center
Fort Lauderdale, Florida, 33316, United States
University of Miami
Miami, Florida, 33101, United States
University of Southern Florida College of Medicine
Tampa, Florida, 33606, United States
Stoger Hospital of Cook County
Chicago, Illinois, 60612, United States
Childrens Memorial Hospital
Chicago, Illinois, 60614, United States
Tulane Medical Center
New Orleans, Louisiana, 70112, United States
University of Maryland
Baltimore, Maryland, 21201, United States
Johns Hopkins University - IMPAACT Site
Baltimore, Maryland, 21287, United States
Children's Hospital of Michigan - IMPAACT Site
Detroit, Michigan, 48201, United States
UMDNJ - IMPAACT Site
Newark, New Jersey, 07103, United States
Mount Sinai Medical Center
New York, New York, 10128, United States
Montefiore Medical Center
The Bronx, New York, 10467, United States
Duke Pediatric Infectious Diseases - IMPAACT Site
Durham, North Carolina, 27710, United States
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104, United States
St. Jude Children's Research Hospital (Memphis) - IMPAACT Site
Memphis, Tennessee, 38105, United States
St. Jude Childrens Research Hospital
Memphis, Tennessee, 38105, United States
University of Puerto Rico
San Juan, 00927, Puerto Rico
Related Publications (1)
Borkar SA, Yin L, Venturi GM, Shen J, Chang KF, Fischer BM, Nepal U, Raplee ID, Sleasman JW, Goodenow MM. Youth Who Control HIV on Antiretroviral Therapy Display Unique Plasma Biomarkers and Cellular Transcriptome Profiles Including DNA Repair and RNA Processing. Cells. 2025 Feb 15;14(4):285. doi: 10.3390/cells14040285.
PMID: 39996757DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Dr. Bob Harris
- Organization
- Westat
Study Officials
- STUDY CHAIR
Bret J Rudy, M.D.
Children's Hospital of Philadelphia
- STUDY CHAIR
John Sleasman, M.D.
University of South Florida, Dept of Pediatrics
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- not applicable
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
June 22, 2007
First Posted
June 26, 2007
Study Start
October 1, 2007
Primary Completion
June 1, 2013
Study Completion
June 1, 2013
Last Updated
March 29, 2017
Results First Posted
June 24, 2016
Record last verified: 2016-05