Preservation and Expansion of T-cell Subsets Following HAART De-intensification to Atazanavir/Ritonavir (ATV/r)
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ClinicalTrials.gov Identifier: NCT00491556 |
Recruitment Status
:
Completed
First Posted
: June 26, 2007
Results First Posted
: June 24, 2016
Last Update Posted
: March 29, 2017
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Condition or disease | Intervention/treatment | Phase |
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HIV Infections | Procedure: Early Initiation of Highly Active Anti-Retroviral Therapy Procedure: Standard Care | Not Applicable |
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 102 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | Preservation and Expansion of T-cell Subsets Following HAART De-intensification to Atazanavir/Ritonavir (ATV/r) in Adolescents With CD4 + T Cells > 350 Cells/mm3 Initiating HAART |
Study Start Date : | October 2007 |
Actual Primary Completion Date : | June 2013 |
Actual Study Completion Date : | June 2013 |

Arm | Intervention/treatment |
---|---|
Experimental: Experimental Arm
Subjects 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.
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Procedure: Early Initiation of Highly Active Anti-Retroviral Therapy
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.
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Standard Care Arm
Subjects 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.
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Procedure: Standard Care
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.
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- Difference in CD4+ T Cell Percentage Between Week 0 and Week 48 [ Time Frame: Week 0 and Week 48 ]
- Difference in CD4+ T Cell Percentage Between Week 48 and Week 152 [ Time Frame: 152 Weeks ]
- Difference in CD4+ T Cell Count Between Week 0 and Week 48 [ Time Frame: 48 weeks ]
- Difference in CD4+ T Cell Count Between Week 48 and Week 152 [ Time Frame: 152 weeks ]
- Difference in CD4+ Naïve T Cell Count Between Week 0 and Week 48 [ Time Frame: 48 weeks ]
- Difference in CD4+ Naïve T Cell Count Between Week 48 and Week 152 [ Time Frame: 152 weeks ]
- Difference in CD4+ Termed Central Memory (TCM) Count Between Week 0 and Week 48 [ Time Frame: 48 weeks ]
- Difference in CD4+ TCM Count Between Week 48 and Week 152 [ Time Frame: 152 weeks ]
- Difference in CD4+ Effector Memory (TEM)Ro Count Between Week 0 and Week 48 [ Time Frame: 48 weeks ]
- Difference in CD4+ TEMRo Count Between Week 48 and Week 152 [ Time Frame: 152 weeks ]
- Difference in CD4+ TEMRa Count Between Week 0 and Week 48 [ Time Frame: 48 weeks ]
- Difference in CD4+ TEMRa Count Between Week 48 and Week 152 [ Time Frame: 152 weeks ]
- Difference in CD8+ Naïve T-Cell Count Between Week 0 and Week 48 [ Time Frame: 48 weeks ]
- Difference in CD8+ Naïve T-Cell Count Between Week 48 and Week 152 [ Time Frame: 152 weeks ]
- Difference in CD8+ TCM Count Between Week 0 and Week 48 [ Time Frame: 48 weeks ]
- Difference in CD8+ TCM Count Between Week 48 and Week 152 [ Time Frame: 152 weeks ]
- Difference in CD8+ TEMRo Count Between Week 0 and Week 48 [ Time Frame: 48 weeks ]
- Difference in CD8+ TEMRo Count Between Week 48 and Week 152 [ Time Frame: 152 weeks ]
- Difference in CD8+ TEMRa Count Between Week 0 and Week 48 [ Time Frame: 48 weeks ]
- Difference in CD8+ TEMRa Count Between Week 48 and Week 152 [ Time Frame: 152 weeks ]
- Difference in CD8 Naïve CD28 Cell Percentage Between Week 0 and Week 48 [ Time Frame: 48 weeks ]
- Difference in CD8 Naïve CD28 Cell Percentage Between Week 48 and Week 152 [ Time Frame: 152 weeks ]
- Difference in CD8 Naïve CD38 Cell Percentage Between Week 0 and Week 48 [ Time Frame: 48 weeks ]
- Difference in CD8 Naïve CD38 Cell Percentage Between Week 48 and Week 152 [ Time Frame: 152 weeks ]
- Difference in CD8 Naïve CD57 Cell Percentage Between Week 0 and Week 48 [ Time Frame: 48 weeks ]
- Difference in CD8 Naïve CD57 Cell Percentage Between Week 48 and Week 152 [ Time Frame: 152 weeks ]
- Difference in CD8 Naïve T-Cell Percentage Expressing Human Leukocyte Antigen-D Related (HLA-DR) Between Week 0 and Week 48 [ Time Frame: 48 weeks ]
- Difference in CD8 Naïve T-Cell Percentage Expressing HLA-DR Between Week 48 and Week 152 [ Time Frame: 152 weeks ]
- Difference in CD8 TCM CD28 Percentage Between Week 0 and Week 48 [ Time Frame: 48 weeks ]
- Difference in CD8 TCM CD28 Percentage Between Week 48 and Week 152 [ Time Frame: 152 weeks ]
- Difference in CD8 TCM CD38 Percentage Between Week 0 and Week 48 [ Time Frame: 48 weeks ]
- Difference in CD8 TCM CD38 Percentage Between Week 48 and Week 152 [ Time Frame: 152 weeks ]
- Difference in CD8 TCM CD57 Percentage Between Week 0 and Week 48 [ Time Frame: 48 weeks ]
- Difference in CD8 TCM CD57 Percentage Between Week 48 and Week 152 [ Time Frame: 152 weeks ]
- Difference in CD8 TCM HLA-DR Percentage Between Week 0 and Week 48 [ Time Frame: 48 weeks ]
- Difference in CD8 TCM HLA-DR Percentage Between Week 48 and Week 152 [ Time Frame: 152 weeks ]
- Difference in CD8 TEMRo CD28 Percentage Between Week 0 and Week 48 [ Time Frame: 48 weeks ]
- Difference in CD8 TEMRo CD28 Percentage Between Week 48 and Week 152 [ Time Frame: 152 weeks ]
- Difference in CD8 TEMRo CD38 Percentage Between Week 0 and Week 48 [ Time Frame: 48 weeks ]
- Difference in CD8 TEMRo CD38 Percentage Between Week 48 and Week 152 [ Time Frame: 152 weeks ]
- Difference in CD8 TEMRo CD57 Percentage Between Week 0 and Week 48 [ Time Frame: 48 weeks ]
- Difference in CD8 TEMRo CD57 Percentage Between Week 48 and Week 152 [ Time Frame: 152 weeks ]
- Difference in CD8 TEMRO HLADR Percentage Between Week 0 and Week 48 [ Time Frame: 48 weeks ]
- Difference in CD8 TEMRo HLA-DR Percentage Between Week 48 and Week 152 [ Time Frame: 152 weeks ]
- Difference in CD8 TEMRa CD28 Percentage Between Week 0 and Week 48 [ Time Frame: 48 weeks ]
- Difference in CD8 TEMRa CD28 Percentage Between Week 48 and Week 152 [ Time Frame: 152 weeks ]
- Difference in CD8 TEMRa CD38 Percentage Between Week 0 and Week 48 [ Time Frame: 48 weeks ]
- Difference in CD8 TEMRa CD38 Percentage Between Week 48 and Week 152 [ Time Frame: 152 weeks ]
- Difference in CD8 TEMRa CD57 Percentage Between Week 0 and Week 48 [ Time Frame: 48 weeks ]
- Difference in CD8 TEMRa CD57 Percentage Between Week 48 and Week 152 [ Time Frame: 152 weeks ]
- Difference in CD8 TEMRa HLA-DR Percentage Between Week 0 and Week 48 [ Time Frame: 48 weeks ]
- Difference in CD8 TEMRa HLA-DR Percentage Between Week 48 and Week 152 [ Time Frame: 152 weeks ]

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
Ages Eligible for Study: | 18 Years to 24 Years (Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria
- 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.
Exclusion Criteria
- 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);
- Any history of an AIDS-defining illness (note: a history of a CD4 + T cell count below 200 cells/mm3 is not an exclusion criterion as long as all other inclusion/exclusion criteria are met);
- 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).

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00491556

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 |
Additional Information:
Responsible Party: | University of North Carolina, Chapel Hill |
ClinicalTrials.gov Identifier: | NCT00491556 History of Changes |
Other Study ID Numbers: |
ATN 061 |
First Posted: | June 26, 2007 Key Record Dates |
Results First Posted: | June 24, 2016 |
Last Update Posted: | March 29, 2017 |
Last Verified: | May 2016 |
Keywords provided by University of North Carolina, Chapel Hill:
Atazanavir/Ritonavir (ATV/r) highly-active antiretroviral therapy (HAART) Treatment Naive |
Additional relevant MeSH terms:
HIV Infections Lentivirus Infections Retroviridae Infections RNA Virus Infections Virus Diseases Sexually Transmitted Diseases, Viral Sexually Transmitted Diseases Immunologic Deficiency Syndromes Immune System Diseases Ritonavir Atazanavir Sulfate |
HIV Protease Inhibitors Protease Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Anti-HIV Agents Anti-Retroviral Agents Antiviral Agents Anti-Infective Agents Cytochrome P-450 CYP3A Inhibitors Cytochrome P-450 Enzyme Inhibitors |