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Impact of Antiretroviral Therapy on Metabolic, Skeletal, and Cardiovascular Parameters

This study has been completed.
Sponsor:
Collaborator:
National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by (Responsible Party):
AIDS Clinical Trials Group
ClinicalTrials.gov Identifier:
NCT00851799
First received: February 24, 2009
Last updated: December 9, 2015
Last verified: December 2015
Results First Received: November 4, 2015  
Study Type: Observational
Study Design: Observational Model: Cohort;   Time Perspective: Prospective
Condition: HIV Infection
Interventions: Drug: Emtricitabine/tenofovir disoproxil fumarate
Drug: Ritonavir
Drug: Atazanavir
Drug: Raltegravir
Drug: Darunavir

  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
Consented and enrolled at AIDS clinical trials units in the United States. Enrollment occurred between June 1, 2009 (date first participant was enrolled) and April 13, 2011 (date last subject was enrolled).

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
334 consented and enrolled; 6 participants who initially enrolled were subsequently found ineligible and excluded from all analyses. Results reported for 328 eligible participants.

Reporting Groups
  Description
Cohort A: ATV/RTV + FTC/TDF

ATV/RTV + FTC/TDF

Emtricitabine/tenofovir disoproxil fumarate (FTC/TDF), ritonavir (RTV), and atazanavir (ATV) to be taken orally, once daily.

Emtricitabine/tenofovir disoproxil fumarate: A combination drug of two nucleoside reverse transcriptase inhibitors (NRTIs) Ritonavir: A protease inhibitor (PI) Atazanavir: A protease inhibitor (PI)

Cohort B: RAL + FTC/TDF

RAL + FTC/TDF

FTC/TDF orally, once daily, and raltegravir (RAL) orally, twice daily.

Emtricitabine/tenofovir disoproxil fumarate: A combination drug of two nucleoside reverse transcriptase inhibitors (NRTIs) Raltegravir: An integrase inhibitor (INI)

Cohort C: DRV/RTV + FTC/TDF

DRV/RTV + FTC/TDF

FTC/TDF, darunavir (DRV), and RTV, orally, once daily.

Emtricitabine/tenofovir disoproxil fumarate: A combination drug of two nucleoside reverse transcriptase inhibitors (NRTIs) Darunavir: A protease inhibitor (PI) Ritonavir: A protease inhibitor (PI)


Participant Flow:   Overall Study
    Cohort A: ATV/RTV + FTC/TDF     Cohort B: RAL + FTC/TDF     Cohort C: DRV/RTV + FTC/TDF  
STARTED     109     106     113  
COMPLETED     93     93     89  
NOT COMPLETED     16     13     24  
Death                 1                 0                 1  
Lost to Follow-up                 5                 3                 10  
Not able to get to clinic                 8                 5                 9  
Not willing to adhere to requirements                 1                 2                 2  
Withdrew consent prior study completion                 1                 2                 1  
Severe Debilitation                 0                 1                 0  
Completed protocol due to pregnancy                 0                 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.
All eligible participants were included in the baseline characteristics.

Reporting Groups
  Description
Cohort A: ATV/RTV + FTC/TDF

ATV/RTV + FTC/TDF

Emtricitabine/tenofovir disoproxil fumarate (FTC/TDF), ritonavir (RTV), and atazanavir (ATV) to be taken orally, once daily.

Emtricitabine/tenofovir disoproxil fumarate: A combination drug of two nucleoside reverse transcriptase inhibitors (NRTIs) Ritonavir: A protease inhibitor (PI) Atazanavir: A protease inhibitor (PI)

Cohort B: RAL + FTC/TDF

RAL + FTC/TDF

FTC/TDF orally, once daily, and raltegravir (RAL) orally, twice daily.

Emtricitabine/tenofovir disoproxil fumarate: A combination drug of two nucleoside reverse transcriptase inhibitors (NRTIs) Raltegravir: An integrase inhibitor (INI)

Cohort C: DRV/RTV + FTC/TDF

DRV/RTV + FTC/TDF

FTC/TDF, darunavir (DRV), and RTV, orally, once daily.

Emtricitabine/tenofovir disoproxil fumarate: A combination drug of two nucleoside reverse transcriptase inhibitors (NRTIs) Darunavir: A protease inhibitor (PI) Ritonavir: A protease inhibitor (PI)

Total Total of all reporting groups

Baseline Measures
    Cohort A: ATV/RTV + FTC/TDF     Cohort B: RAL + FTC/TDF     Cohort C: DRV/RTV + FTC/TDF     Total  
Number of Participants  
[units: participants]
  109     106     113     328  
Age  
[units: participants]
       
<=18 years     0     0     0     0  
Between 18 and 65 years     107     105     113     325  
>=65 years     2     1     0     3  
Age  
[units: years]
Median (Inter-Quartile Range)
  37  
  (31 to 45)  
  36  
  (27 to 44)  
  35  
  (27 to 46)  
  36  
  (28 to 45)  
Gender  
[units: participants]
       
Female     10     12     12     34  
Male     99     94     101     294  
Race/Ethnicity, Customized [1]
[units: participants]
       
White Non-Hispanic     53     43     48     144  
Black Non-Hispanic     34     34     37     105  
Hispanic (Regardless of Race)     20     20     25     65  
Asian, Pacific Islander     2     5     1     8  
American Indian, Alaskan Native     0     2     1     3  
More than one race     0     1     1     2  
Unknown/missing     0     1     0     1  
HIV-1 RNA [2]
[units: log10 copies/mL]
Median (Inter-Quartile Range)
  4.6  
  (4.0 to 5.1)  
  4.5  
  (4.1 to 5.1)  
  4.5  
  (4.0 to 4.9)  
  4.5  
  (4.0 to 5.1)  
CD4+ T-cell count [3]
[units: cells/mm^3]]
Median (Inter-Quartile Range)
  350  
  (211 to 461)  
  343  
  (185 to 445)  
  355  
  (207 to 461)  
  349  
  (203 to 455)  
[1] Race/Ethnicity was collected prior to study entry.
[2] HIV-1 RNA was calculated as the geometric mean of the two most recent HIV-1 RNA (log 10 copies/mL) obtained on or before study entry. In the event that these two values differed by more than 1 log10 copy/mL, the outlying value (based on review of all HIV-1 RNA levels available prior to study entry by the study virologist) was excluded with the baseline level determined by the remaining sample. Note that screening HIV-1 RNA values were not used in the calculation of baseline HIV-1 RNA levels.
[3] CD4+ T-cell counts were calculated as the mean of the two most recent values available on or before study entry.



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Annual Rate of Change in Right Common Carotid Artery Intima-media Thickness (CIMT)   [ Time Frame: Study entry, week 144 ]

2.  Primary:   Change in Brachial Artery (BA) Flow Mediated Dilation (FMD) From Study Entry to Week 24   [ Time Frame: Study entry, week 24 ]

3.  Secondary:   Change in Brachial Artery Flow Mediated Dilation (FMD) From Study Entry to Weeks 4 and 48   [ Time Frame: Study entry, weeks 4 and 48 ]

4.  Secondary:   Change in Absolute Flow Mediated Dilation (FMD) From Study Entry to Weeks 4, 24 and 48   [ Time Frame: Study entry, weeks 4, 24 and 48 ]

5.  Secondary:   Percent Change in Bone Mineral Density (BMD) of the Hip From Study Entry to Week 96   [ Time Frame: Study entry, week 96 ]

6.  Secondary:   Percent Change in Bone Mineral Density (BMD) of the Lumber Spine From Study Entry to Week 96   [ Time Frame: Study entry, week 96 ]

7.  Secondary:   Percent Change in Bone Mineral Density (BMD) of the Total Body From Study Entry to Week 96   [ Time Frame: Study entry, week 96 ]

8.  Secondary:   Percent Change in Total Limb Fat From Study Entry to Week 96   [ Time Frame: Study entry, week 96 ]

9.  Secondary:   Percent Change in Trunk Fat From Study Entry to Week 96   [ Time Frame: Study entry, week 96 ]

10.  Secondary:   Percent Change in Lean Mass From Study Entry to Week 96   [ Time Frame: Study entry, week 96 ]

11.  Secondary:   Percent Change in Visceral Abdominal Fat (VAT) From Study Entry to Week 96   [ Time Frame: Study entry, week 96 ]

12.  Secondary:   Percent Change in Subcutaneous Abdominal Fat (SAT) From Study Entry to Week 96   [ Time Frame: Study entry, week 96 ]

13.  Secondary:   CD4+ T-cell Count at Study Entry and Weeks 24, 48, 96 and 144   [ Time Frame: Study entry, weeks 24, 48, 96 and 144 ]

14.  Secondary:   Change in CD4+ T-cell Count From Study Entry to Weeks 24, 48, 96 and 144   [ Time Frame: Study entry to weeks 24, 48, 96, and 144 ]

15.  Secondary:   Change in Fasting Total Cholesterol (TC) From Study Entry to Weeks 4, 24, 48 and 96   [ Time Frame: Study entry, weeks 4, 24, 48 and 96 ]

16.  Secondary:   Change in Fasting Triglyceride (TG) From Study Entry to Weeks 4, 24, 48 and 96   [ Time Frame: Study entry, weeks 4, 24, 48 and 96 ]

17.  Secondary:   Change in Fasting High-density Lipoprotein Cholesterol (HDL-C) From Study Entry to Weeks 4, 24, 48 and 96   [ Time Frame: Study entry, weeks 4, 24, 48 and 96 ]

18.  Secondary:   Change in Fasting Calculated Low-density Lipoprotein Cholesterol (LDL-C) From Study Entry to Weeks 4, 24, 48 and 96   [ Time Frame: Study entry, weeks 4, 24, 48 and 96 ]

19.  Secondary:   Change in Fasting Glucose Level From Study Entry to Weeks 4, 24, 48 and 96   [ Time Frame: Study entry, weeks 4, 24, 48 and 96 ]

20.  Secondary:   Change in Fasting Insulin Level From Study Entry to Weeks 4, 24, 48 and 96   [ Time Frame: Study entry, weeks 4, 24, 48 and 96 ]

21.  Secondary:   Fold Change in D-dimer From Study Entry to Weeks 48 and 96   [ Time Frame: Study entry, weeks 48 and 96 ]

22.  Secondary:   Fold Change in High Sensitivity C-reactive Protein (hsCRP) From Study Entry to Weeks 48 and 96   [ Time Frame: Study entry, weeks 48 and 96 ]

23.  Secondary:   Fold Change in Interleukin-6 (IL-6) From Study Entry to Weeks 48 and 96   [ Time Frame: Study entry, weeks 48 and 96 ]

24.  Secondary:   Fold Change in Soluble CD14 From Study Entry to Weeks 48 and 96   [ Time Frame: Study entry, weeks 48 and 96 ]

25.  Secondary:   Fold Change in Soluble CD163 From Study Entry to Weeks 48 and 96   [ Time Frame: Study entry, weeks 48 and 96 ]

26.  Secondary:   Fold Change in Percent Expression of CD38+HLADR+ on CD4+ (Percent) From Study Entry to Weeks 24 and 96   [ Time Frame: Study entry, weeks 24 and 96 ]

27.  Secondary:   Fold Change in Percent Expression of CD38+HLADR+ on CD8+ (Percent) From Study Entry to Weeks 24 and 96   [ Time Frame: Study entry, weeks 24 and 96 ]


  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: ACTG Clinicaltrials.gov Coordinator
Organization: ACTG Network Coordinating Center, Social and Scientific Systems, Inc.
phone: (301) 628-3313
e-mail: ACTGCT.Gov@s-3.com


Publications of Results:

Other Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: AIDS Clinical Trials Group
ClinicalTrials.gov Identifier: NCT00851799     History of Changes
Other Study ID Numbers: ACTG A5260s
1U01AI068636 ( US NIH Grant/Contract Award Number )
ACTG A5257 metabolic substudy
Study First Received: February 24, 2009
Results First Received: November 4, 2015
Last Updated: December 9, 2015
Health Authority: United States: Federal Government