Preservation and Expansion of T-cell Subsets Following HAART De-intensification to Atazanavir/Ritonavir (ATV/r)

This study has been completed.
Sponsor:
Collaborators:
National Institute on Drug Abuse (NIDA)
National Institute of Mental Health (NIMH)
International Maternal Pediatric Adolescent AIDS Clinical Trials Group
Information provided by (Responsible Party):
Westat
ClinicalTrials.gov Identifier:
NCT00491556
First received: June 22, 2007
Last updated: May 16, 2016
Last verified: May 2016
Results First Received: March 18, 2016  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: HIV Infections
Interventions: Procedure: Early Initiation of Highly Active Anti-Retroviral Therapy
Procedure: Standard Care

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
This research was conducted at 23 clinical sites. Accrual was open between August 2007 and June 2010.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Experimental-Early Initiation of HAART (EXP) Began HAART consisting of TDF/FTC/ATV/r (preferred regimen), AZT/3TC/ATV/r, or other recommended NRTI HAART backbone with ATV/r upon entry to study. Subjects who achieved virologic control by week 24 (viral load (VL) < 100 copies/ml) and maintained good control through 48 weeks then entered deintensification (de-int) to ATV/r alone and were followed for two years.
Standard Care (STAND) Began HAART with ATV/r under the current DHHS guidelines (CD4+ T cells below 350 cells/mm3 or for other clinical concerns as outlined in the recommendations and as determined by the site clinician).

Participant Flow for 2 periods

Period 1:   Entry-Week (WK) 48: EXP/Standard Care
    Experimental-Early Initiation of HAART (EXP)     Standard Care (STAND)  
STARTED     75     27  
Wk 24 VL Suppressed (EXP)/WK 24 (STAND)     53     27  
COMPLETED     49     27  
NOT COMPLETED     26     0  
Lost to Follow-up                 1                 0  
Physician Decision                 1                 0  
Withdrawal by Subject                 1                 0  
Moved Out of Area                 2                 0  
Failure to Suppress VL at Week 24                 11                 0  
VL Failure at Week 24                 2                 0  
Adherence Issues                 2                 0  
Toxicity                 3                 0  
Not Specified                 3                 0  

Period 2:   Wk 48-152: EXP (On De-Int)/Standard Care
    Experimental-Early Initiation of HAART (EXP)     Standard Care (STAND)  
STARTED     49     27  
COMPLETED     25     22  
NOT COMPLETED     24     5  
Lost to Follow-up                 2                 2  
Pregnancy                 2                 0  
Moved Out of Area                 2                 1  
VL Failure After Week 48                 5                 0  
CD4 Failure                 2                 0  
Adherence Issues                 5                 0  
Toxicity                 2                 0  
End of Funding                 2                 0  
Not Specified                 2                 0  
Incarceration                 0                 1  
Death of Participant                 0                 1  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
75 subjects were randomized to the experimental arm, however 2 subjects withdrew from the study at the pre-entry visit. Therefore, only 73 experimental arm subjects were available for the baseline analyses.

Reporting Groups
  Description
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.

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.

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.

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.

Total Total of all reporting groups

Baseline Measures
    Experimental Arm     Standard Care Arm     Total  
Number of Participants  
[units: participants]
  73     27     100  
Age, Customized  
[units: participants]
     
18-20 years     31     10     41  
21-24 years     42     17     59  
Gender  
[units: participants]
     
Female     9     4     13  
Male     64     23     87  
Race/Ethnicity, Customized  
[units: participants]
     
White non-Hispanic     6     0     6  
Black non-Hispanic     47     23     70  
Hispanic     17     2     19  
Asian     2     1     3  
Other     1     1     2  
Region of Enrollment  
[units: participants]
     
United States     72     27     99  
Puerto Rico     1     0     1  



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Difference in CD4+ T Cell Percentage Between Week 0 and Week 48   [ Time Frame: Week 0 and Week 48 ]

2.  Primary:   Difference in CD4+ T Cell Percentage Between Week 48 and Week 152   [ Time Frame: 152 Weeks ]

3.  Secondary:   Difference in CD4+ T Cell Count Between Week 0 and Week 48   [ Time Frame: 48 weeks ]

4.  Secondary:   Difference in CD4+ T Cell Count Between Week 48 and Week 152   [ Time Frame: 152 weeks ]

5.  Secondary:   Difference in CD4+ Naïve T Cell Count Between Week 0 and Week 48   [ Time Frame: 48 weeks ]

6.  Secondary:   Difference in CD4+ Naïve T Cell Count Between Week 48 and Week 152   [ Time Frame: 152 weeks ]

7.  Secondary:   Difference in CD4+ Termed Central Memory (TCM) Count Between Week 0 and Week 48   [ Time Frame: 48 weeks ]

8.  Secondary:   Difference in CD4+ TCM Count Between Week 48 and Week 152   [ Time Frame: 152 weeks ]

9.  Secondary:   Difference in CD4+ Effector Memory (TEM)Ro Count Between Week 0 and Week 48   [ Time Frame: 48 weeks ]

10.  Secondary:   Difference in CD4+ TEMRo Count Between Week 48 and Week 152   [ Time Frame: 152 weeks ]

11.  Secondary:   Difference in CD4+ TEMRa Count Between Week 0 and Week 48   [ Time Frame: 48 weeks ]

12.  Secondary:   Difference in CD4+ TEMRa Count Between Week 48 and Week 152   [ Time Frame: 152 weeks ]

13.  Secondary:   Difference in CD8+ Naïve T-Cell Count Between Week 0 and Week 48   [ Time Frame: 48 weeks ]

14.  Secondary:   Difference in CD8+ Naïve T-Cell Count Between Week 48 and Week 152   [ Time Frame: 152 weeks ]

15.  Secondary:   Difference in CD8+ TCM Count Between Week 0 and Week 48   [ Time Frame: 48 weeks ]

16.  Secondary:   Difference in CD8+ TCM Count Between Week 48 and Week 152   [ Time Frame: 152 weeks ]

17.  Secondary:   Difference in CD8+ TEMRo Count Between Week 0 and Week 48   [ Time Frame: 48 weeks ]

18.  Secondary:   Difference in CD8+ TEMRo Count Between Week 48 and Week 152   [ Time Frame: 152 weeks ]

19.  Secondary:   Difference in CD8+ TEMRa Count Between Week 0 and Week 48   [ Time Frame: 48 weeks ]

20.  Secondary:   Difference in CD8+ TEMRa Count Between Week 48 and Week 152   [ Time Frame: 152 weeks ]

21.  Secondary:   Difference in CD8 Naïve CD28 Cell Percentage Between Week 0 and Week 48   [ Time Frame: 48 weeks ]

22.  Secondary:   Difference in CD8 Naïve CD28 Cell Percentage Between Week 48 and Week 152   [ Time Frame: 152 weeks ]

23.  Secondary:   Difference in CD8 Naïve CD38 Cell Percentage Between Week 0 and Week 48   [ Time Frame: 48 weeks ]

24.  Secondary:   Difference in CD8 Naïve CD38 Cell Percentage Between Week 48 and Week 152   [ Time Frame: 152 weeks ]

25.  Secondary:   Difference in CD8 Naïve CD57 Cell Percentage Between Week 0 and Week 48   [ Time Frame: 48 weeks ]

26.  Secondary:   Difference in CD8 Naïve CD57 Cell Percentage Between Week 48 and Week 152   [ Time Frame: 152 weeks ]

27.  Secondary:   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 ]

28.  Secondary:   Difference in CD8 Naïve T-Cell Percentage Expressing HLA-DR Between Week 48 and Week 152   [ Time Frame: 152 weeks ]

29.  Secondary:   Difference in CD8 TCM CD28 Percentage Between Week 0 and Week 48   [ Time Frame: 48 weeks ]

30.  Secondary:   Difference in CD8 TCM CD28 Percentage Between Week 48 and Week 152   [ Time Frame: 152 weeks ]

31.  Secondary:   Difference in CD8 TCM CD38 Percentage Between Week 0 and Week 48   [ Time Frame: 48 weeks ]

32.  Secondary:   Difference in CD8 TCM CD38 Percentage Between Week 48 and Week 152   [ Time Frame: 152 weeks ]

33.  Secondary:   Difference in CD8 TCM CD57 Percentage Between Week 0 and Week 48   [ Time Frame: 48 weeks ]

34.  Secondary:   Difference in CD8 TCM CD57 Percentage Between Week 48 and Week 152   [ Time Frame: 152 weeks ]

35.  Secondary:   Difference in CD8 TCM HLA-DR Percentage Between Week 0 and Week 48   [ Time Frame: 48 weeks ]

36.  Secondary:   Difference in CD8 TCM HLA-DR Percentage Between Week 48 and Week 152   [ Time Frame: 152 weeks ]

37.  Secondary:   Difference in CD8 TEMRo CD28 Percentage Between Week 0 and Week 48   [ Time Frame: 48 weeks ]

38.  Secondary:   Difference in CD8 TEMRo CD28 Percentage Between Week 48 and Week 152   [ Time Frame: 152 weeks ]

39.  Secondary:   Difference in CD8 TEMRo CD38 Percentage Between Week 0 and Week 48   [ Time Frame: 48 weeks ]

40.  Secondary:   Difference in CD8 TEMRo CD38 Percentage Between Week 48 and Week 152   [ Time Frame: 152 weeks ]

41.  Secondary:   Difference in CD8 TEMRo CD57 Percentage Between Week 0 and Week 48   [ Time Frame: 48 weeks ]

42.  Secondary:   Difference in CD8 TEMRo CD57 Percentage Between Week 48 and Week 152   [ Time Frame: 152 weeks ]

43.  Secondary:   Difference in CD8 TEMRO HLADR Percentage Between Week 0 and Week 48   [ Time Frame: 48 weeks ]

44.  Secondary:   Difference in CD8 TEMRo HLA-DR Percentage Between Week 48 and Week 152   [ Time Frame: 152 weeks ]

45.  Secondary:   Difference in CD8 TEMRa CD28 Percentage Between Week 0 and Week 48   [ Time Frame: 48 weeks ]

46.  Secondary:   Difference in CD8 TEMRa CD28 Percentage Between Week 48 and Week 152   [ Time Frame: 152 weeks ]

47.  Secondary:   Difference in CD8 TEMRa CD38 Percentage Between Week 0 and Week 48   [ Time Frame: 48 weeks ]

48.  Secondary:   Difference in CD8 TEMRa CD38 Percentage Between Week 48 and Week 152   [ Time Frame: 152 weeks ]

49.  Secondary:   Difference in CD8 TEMRa CD57 Percentage Between Week 0 and Week 48   [ Time Frame: 48 weeks ]

50.  Secondary:   Difference in CD8 TEMRa CD57 Percentage Between Week 48 and Week 152   [ Time Frame: 152 weeks ]

51.  Secondary:   Difference in CD8 TEMRa HLA-DR Percentage Between Week 0 and Week 48   [ Time Frame: 48 weeks ]

52.  Secondary:   Difference in CD8 TEMRa HLA-DR Percentage Between Week 48 and Week 152   [ Time Frame: 152 weeks ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Dr. Bob Harris
Organization: Westat
phone: 301-251-1500
e-mail: bobharris@westat.com



Responsible Party: Westat
ClinicalTrials.gov Identifier: NCT00491556     History of Changes
Other Study ID Numbers: ATN 061
Study First Received: June 22, 2007
Results First Received: March 18, 2016
Last Updated: May 16, 2016
Health Authority: United States: Federal Government