Trial Outcomes & Findings for Impact of Antiretroviral Therapy on Metabolic, Skeletal, and Cardiovascular Parameters (NCT NCT00851799)

NCT ID: NCT00851799

Last Updated: 2016-01-13

Results Overview

Right common carotid artery intima-media thickness was measured by ultrasound scan at study entry and weeks 48, 96 and 144. The annual rate of change in right common carotid artery intima-media thickness (CIMT) was estimated over 144 weeks from study entry using mixed effects linear regression model that adjusted for screening HIV-1 RNA level and Framingham risk score stratification factors.

Recruitment status

COMPLETED

Target enrollment

334 participants

Primary outcome timeframe

Study entry, week 144

Results posted on

2016-01-13

Participant Flow

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).

334 consented and enrolled; 6 participants who initially enrolled were subsequently found ineligible and excluded from all analyses. Results reported for 328 eligible participants.

Participant milestones

Participant milestones
Measure
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)
Overall Study
STARTED
109
106
113
Overall Study
COMPLETED
93
93
89
Overall Study
NOT COMPLETED
16
13
24

Reasons for withdrawal

Reasons for withdrawal
Measure
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)
Overall Study
Death
1
0
1
Overall Study
Lost to Follow-up
5
3
10
Overall Study
Not able to get to clinic
8
5
9
Overall Study
Not willing to adhere to requirements
1
2
2
Overall Study
Withdrew consent prior study completion
1
2
1
Overall Study
Severe Debilitation
0
1
0
Overall Study
Completed protocol due to pregnancy
0
0
1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Cohort A: ATV/RTV + FTC/TDF
n=109 Participants
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
n=106 Participants
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
n=113 Participants
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
n=328 Participants
Total of all reporting groups
Age, Categorical
<=18 years
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
0 Participants
n=4 Participants
Age, Categorical
Between 18 and 65 years
107 Participants
n=5 Participants
105 Participants
n=7 Participants
113 Participants
n=5 Participants
325 Participants
n=4 Participants
Age, Categorical
>=65 years
2 Participants
n=5 Participants
1 Participants
n=7 Participants
0 Participants
n=5 Participants
3 Participants
n=4 Participants
Age, Continuous
37 years
n=5 Participants
36 years
n=7 Participants
35 years
n=5 Participants
36 years
n=4 Participants
Sex: Female, Male
Female
10 Participants
n=5 Participants
12 Participants
n=7 Participants
12 Participants
n=5 Participants
34 Participants
n=4 Participants
Sex: Female, Male
Male
99 Participants
n=5 Participants
94 Participants
n=7 Participants
101 Participants
n=5 Participants
294 Participants
n=4 Participants
Race/Ethnicity, Customized
White Non-Hispanic
53 participants
n=5 Participants
43 participants
n=7 Participants
48 participants
n=5 Participants
144 participants
n=4 Participants
Race/Ethnicity, Customized
Black Non-Hispanic
34 participants
n=5 Participants
34 participants
n=7 Participants
37 participants
n=5 Participants
105 participants
n=4 Participants
Race/Ethnicity, Customized
Hispanic (Regardless of Race)
20 participants
n=5 Participants
20 participants
n=7 Participants
25 participants
n=5 Participants
65 participants
n=4 Participants
Race/Ethnicity, Customized
Asian, Pacific Islander
2 participants
n=5 Participants
5 participants
n=7 Participants
1 participants
n=5 Participants
8 participants
n=4 Participants
Race/Ethnicity, Customized
American Indian, Alaskan Native
0 participants
n=5 Participants
2 participants
n=7 Participants
1 participants
n=5 Participants
3 participants
n=4 Participants
Race/Ethnicity, Customized
More than one race
0 participants
n=5 Participants
1 participants
n=7 Participants
1 participants
n=5 Participants
2 participants
n=4 Participants
Race/Ethnicity, Customized
Unknown/missing
0 participants
n=5 Participants
1 participants
n=7 Participants
0 participants
n=5 Participants
1 participants
n=4 Participants
HIV-1 RNA
4.6 log10 copies/mL
n=5 Participants
4.5 log10 copies/mL
n=7 Participants
4.5 log10 copies/mL
n=5 Participants
4.5 log10 copies/mL
n=4 Participants
CD4+ T-cell count
350 cells/mm^3]
n=5 Participants
343 cells/mm^3]
n=7 Participants
355 cells/mm^3]
n=5 Participants
349 cells/mm^3]
n=4 Participants

PRIMARY outcome

Timeframe: Study entry, week 144

Population: Intention to treat; all eligible participants were included in the analysis. Participants were analyzed per original assigned randomized treatment and stratification in ACTG A5257.

Right common carotid artery intima-media thickness was measured by ultrasound scan at study entry and weeks 48, 96 and 144. The annual rate of change in right common carotid artery intima-media thickness (CIMT) was estimated over 144 weeks from study entry using mixed effects linear regression model that adjusted for screening HIV-1 RNA level and Framingham risk score stratification factors.

Outcome measures

Outcome measures
Measure
Cohort A: ATV/RTV + FTC/TDF
n=109 Participants
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
n=106 Participants
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
n=113 Participants
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)
Annual Rate of Change in Right Common Carotid Artery Intima-media Thickness (CIMT)
8.2 micron/year
Interval 5.6 to 10.8
10.7 micron/year
Interval 9.2 to 12.2
12.9 micron/year
Interval 10.3 to 15.5

PRIMARY outcome

Timeframe: Study entry, week 24

Population: Intention to treat; all eligible participants with available data were included. Participants were analyzed per original assigned randomized treatment and stratification in ACTG A5257.

Brachial artery flow mediated dilation was measured by brachial artery reactivity tests. All results reflect measures captured from participants who reported fasting and not smoking for at least 8 hours prior to FMD assessments. The change from study entry to week 24 in brachial artery FMD (%) was defined as the maximum FMD (%) calculated from resting heart rate (RH) 60 seconds and RH 90 seconds, relative to resting brachial artery diameter.

Outcome measures

Outcome measures
Measure
Cohort A: ATV/RTV + FTC/TDF
n=103 Participants
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
n=102 Participants
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
n=107 Participants
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)
Change in Brachial Artery (BA) Flow Mediated Dilation (FMD) From Study Entry to Week 24
-0.05 percent
Interval -1.51 to 1.6
-0.27 percent
Interval -1.61 to 1.55
0.15 percent
Interval -1.39 to 1.56

SECONDARY outcome

Timeframe: Study entry, weeks 4 and 48

Population: Intention to treat; all eligible participants with available data were included. Participants were analyzed per original assigned randomized treatment and stratification in ACTG A5257.

Brachial artery flow mediated dilation was measured by brachial artery reactivity tests. All results reflect measures captured from participants who reported fasting and not smoking for at least 8 hours prior to FMD assessments. The change from study entry to weeks 4 and 48 in brachial artery FMD (%) was defined as the maximum FMD (%) calculated from resting heart rate (RH) 60 seconds and RH 90 seconds, relative to resting brachial artery diameter.

Outcome measures

Outcome measures
Measure
Cohort A: ATV/RTV + FTC/TDF
n=103 Participants
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
n=102 Participants
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
n=107 Participants
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)
Change in Brachial Artery Flow Mediated Dilation (FMD) From Study Entry to Weeks 4 and 48
Change from study entry to week 4
-0.04 percent
Interval -0.54 to 0.46
0.22 percent
Interval -0.36 to 0.81
-0.15 percent
Interval -0.65 to 0.34
Change in Brachial Artery Flow Mediated Dilation (FMD) From Study Entry to Weeks 4 and 48
Change from study entry to week 48
-0.04 percent
Interval -0.6 to 0.52
-0.08 percent
Interval -0.73 to 0.58
-0.11 percent
Interval -0.71 to 0.49

SECONDARY outcome

Timeframe: Study entry, weeks 4, 24 and 48

Population: Intention to treat; all eligible participants with available data were included. Participants were analyzed per original assigned randomized treatment and stratification in ACTG A5257.

The change in absolute FMD was defined as the maximum absolute FMD from the RH 60 and 90 second measurements, from study entry to weeks 4, 24, and 48 (unit of measure millimeters). All results reflect measures captured from participants who reported fasting and not smoking for at least 8 hours prior to FMD assessments.

Outcome measures

Outcome measures
Measure
Cohort A: ATV/RTV + FTC/TDF
n=103 Participants
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
n=102 Participants
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
n=107 Participants
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)
Change in Absolute Flow Mediated Dilation (FMD) From Study Entry to Weeks 4, 24 and 48
Change from study entry to week 4
0.002 mm
Standard Deviation 0.100
0.012 mm
Standard Deviation 0.105
-0.005 mm
Standard Deviation 0.102
Change in Absolute Flow Mediated Dilation (FMD) From Study Entry to Weeks 4, 24 and 48
Change from study entry to week 24
-0.002 mm
Standard Deviation 0.103
-0.004 mm
Standard Deviation 0.101
0.008 mm
Standard Deviation 0.116
Change in Absolute Flow Mediated Dilation (FMD) From Study Entry to Weeks 4, 24 and 48
Change from study entry to week 48
0.002 mm
Standard Deviation 0.111
0.005 mm
Standard Deviation 0.120
-0.001 mm
Standard Deviation 0.119

SECONDARY outcome

Timeframe: Study entry, week 96

Population: Intention to treat; all eligible participants with available data were included in the analysis. Participants were analyzed per original assigned randomized treatment and stratification in ACTG A5257

Bone mineral density (BMD) of the hip was evaluated by dual-energy x-ray absorptiometry (DXA) scans at study entry and study week 96. The percent change was calculated as ((week 96 value - study entry value) / study entry value)) x 100.

Outcome measures

Outcome measures
Measure
Cohort A: ATV/RTV + FTC/TDF
n=98 Participants
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
n=94 Participants
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
n=96 Participants
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)
Percent Change in Bone Mineral Density (BMD) of the Hip From Study Entry to Week 96
-3.7 percent
Interval -5.7 to -1.4
-2.2 percent
Interval -4.5 to 0.4
-3.3 percent
Interval -5.2 to -0.9

SECONDARY outcome

Timeframe: Study entry, week 96

Population: Intention to treat; all eligible participants with available data were included in the analysis. Participants were analyzed per original assigned randomized treatment and stratification in ACTG A5257.

Bone mineral density (BMD) of the lumber spine was evaluated by dual-energy x-ray absorptiometry (DXA) scans at study entry and study week 96. The percent change was calculated as ((week 96 value - study entry value) / study entry value)) x 100.

Outcome measures

Outcome measures
Measure
Cohort A: ATV/RTV + FTC/TDF
n=99 Participants
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
n=94 Participants
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
n=96 Participants
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)
Percent Change in Bone Mineral Density (BMD) of the Lumber Spine From Study Entry to Week 96
-4.0 percent
Interval -6.5 to -0.3
-1.6 percent
Interval -3.6 to 0.9
-3.1 percent
Interval -5.2 to -0.8

SECONDARY outcome

Timeframe: Study entry, week 96

Population: Intention to treat; all eligible participants with available data were included in the analysis. Participants were analyzed per original assigned randomized treatment and stratification in ACTG A5257.

Bone mineral density (BMD) of the total body was evaluated by dual-energy x-ray absorptiometry (DXA) scans at study entry and study week 96. The percent change was calculated as ((week 96 value - study entry value) / study entry value)) x 100.

Outcome measures

Outcome measures
Measure
Cohort A: ATV/RTV + FTC/TDF
n=98 Participants
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
n=94 Participants
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
n=97 Participants
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)
Percent Change in Bone Mineral Density (BMD) of the Total Body From Study Entry to Week 96
-1.9 percent
Interval -3.7 to -1.0
-0.9 percent
Interval -2.7 to 0.6
-1.0 percent
Interval -2.3 to 0.5

SECONDARY outcome

Timeframe: Study entry, week 96

Population: Intention to treat; all eligible participants with available data were included in the analysis. Participants were analyzed per original assigned randomized treatment and stratification in ACTG A5257.

Total limb fat was evaluated by dual-energy x-ray absorptiometry (DXA) scans at study entry and week 96. The percent change was calculated as ((week 96 value - study entry value) / study entry value)) x 100.

Outcome measures

Outcome measures
Measure
Cohort A: ATV/RTV + FTC/TDF
n=98 Participants
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
n=94 Participants
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
n=97 Participants
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)
Percent Change in Total Limb Fat From Study Entry to Week 96
9.8 percent
Interval -3.7 to 21.3
6.3 percent
Interval -7.5 to 27.7
7.9 percent
Interval -5.8 to 22.9

SECONDARY outcome

Timeframe: Study entry, week 96

Population: Intention to treat; all eligible participants with available data were included in the analysis. Participants were analyzed per original assigned randomized treatment and stratification in ACTG A5257.

Trunk fat was evaluated by dual-energy x-ray absorptiometry (DXA) scans at study entry and week 96. The percent change was calculated as ((week 96 value - study entry value) / study entry value)) x 100.

Outcome measures

Outcome measures
Measure
Cohort A: ATV/RTV + FTC/TDF
n=98 Participants
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
n=94 Participants
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
n=97 Participants
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)
Percent Change in Trunk Fat From Study Entry to Week 96
10.8 percent
Interval -3.4 to 27.7
13.5 percent
Interval -5.3 to 38.3
9.7 percent
Interval -3.7 to 33.6

SECONDARY outcome

Timeframe: Study entry, week 96

Population: Intention to treat; all eligible participants with available data were included in the analysis. Participants were analyzed per original assigned randomized treatment and stratification in ACTG A5257.

Lean mass was evaluated by dual-energy x-ray absorptiometry (DXA) scans at study entry and week 96. The percent change was calculated as ((week 96 value - study entry value) / study entry value)) x 100.

Outcome measures

Outcome measures
Measure
Cohort A: ATV/RTV + FTC/TDF
n=98 Participants
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
n=94 Participants
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
n=97 Participants
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)
Percent Change in Lean Mass From Study Entry to Week 96
1.8 percent
Interval -1.2 to 4.7
1.7 percent
Interval -1.8 to 5.0
0.1 percent
Interval -2.1 to 2.8

SECONDARY outcome

Timeframe: Study entry, week 96

Population: Intention to treat; all eligible participants with available data were included in the analysis. Participants were analyzed per original assigned randomized treatment and stratification in ACTG A5257.

Visceral abdominal fat (VAT) was evaluated by single slice abdominal computerized tomography scans at study entry and week 96. The percent change was calculated as as ((week 96 value - study entry value) / study entry value)) x 100.

Outcome measures

Outcome measures
Measure
Cohort A: ATV/RTV + FTC/TDF
n=97 Participants
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
n=95 Participants
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
n=94 Participants
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)
Percent Change in Visceral Abdominal Fat (VAT) From Study Entry to Week 96
10.7 percent
Interval -12.0 to 50.2
16.2 percent
Interval -7.9 to 43.3
9.5 percent
Interval -8.7 to 37.8

SECONDARY outcome

Timeframe: Study entry, week 96

Population: Intention to treat; all eligible participants with available data were included in the analysis. Participants were analyzed per original assigned randomized treatment and stratification in ACTG A5257.

Subcutaneous abdominal fat (SAT) was evaluated by single slice abdominal computerized tomography scans at study entry and week 96. The percent change was calculated as ((week 96 value - study entry value) / study entry value)) x 100.

Outcome measures

Outcome measures
Measure
Cohort A: ATV/RTV + FTC/TDF
n=97 Participants
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
n=95 Participants
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
n=94 Participants
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)
Percent Change in Subcutaneous Abdominal Fat (SAT) From Study Entry to Week 96
10.3 percent
Interval -5.9 to 26.5
11.8 percent
Interval -6.5 to 36.1
11.4 percent
Interval -7.9 to 33.4

SECONDARY outcome

Timeframe: Study entry, weeks 24, 48, 96 and 144

Population: Intention to treat; all eligible participants with available data were included. Missing data were assumed missing completely at random. Participants were analyzed per original assigned randomized treatment in ACTG A5257.

The absolute levels of CD4+ T-cell counts (cells/mm\^3) measured at study entry and weeks 24, 48, 96 and 144.

Outcome measures

Outcome measures
Measure
Cohort A: ATV/RTV + FTC/TDF
n=109 Participants
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
n=106 Participants
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
n=113 Participants
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)
CD4+ T-cell Count at Study Entry and Weeks 24, 48, 96 and 144
Study Entry
350 cell/mm^3
Interval 211.0 to 461.0
343 cell/mm^3
Interval 185.0 to 445.0
355 cell/mm^3
Interval 207.0 to 461.0
CD4+ T-cell Count at Study Entry and Weeks 24, 48, 96 and 144
Week 48
573 cell/mm^3
Interval 414.0 to 716.0
496 cell/mm^3
Interval 367.0 to 689.0
528 cell/mm^3
Interval 355.0 to 627.0
CD4+ T-cell Count at Study Entry and Weeks 24, 48, 96 and 144
Week 96
634 cell/mm^3
Interval 452.0 to 768.0
569 cell/mm^3
Interval 416.0 to 717.0
567 cell/mm^3
Interval 417.0 to 749.0
CD4+ T-cell Count at Study Entry and Weeks 24, 48, 96 and 144
Week 24
509 cell/mm^3
Interval 356.0 to 653.0
445 cell/mm^3
Interval 348.0 to 610.0
464 cell/mm^3
Interval 299.0 to 592.0
CD4+ T-cell Count at Study Entry and Weeks 24, 48, 96 and 144
Week 144
658 cell/mm^3
Interval 478.0 to 834.0
613 cell/mm^3
Interval 437.0 to 801.0
560 cell/mm^3
Interval 431.0 to 756.0

SECONDARY outcome

Timeframe: Study entry to weeks 24, 48, 96, and 144

Population: Intention to treat; all eligible participants with available data were included. Missing data were assumed missing completely at random. Participants were analyzed per original assigned randomized treatment in ACTG A5257.

Change was calculated as (CD4+ T-cell count at week 24, 48, 96, or 144) - (CD4+ T-cell count at study entry).

Outcome measures

Outcome measures
Measure
Cohort A: ATV/RTV + FTC/TDF
n=107 Participants
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
n=99 Participants
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
n=108 Participants
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)
Change in CD4+ T-cell Count From Study Entry to Weeks 24, 48, 96 and 144
Change from study entry to week 24
161 cell/mm^3
Interval 91.0 to 252.0
133 cell/mm^3
Interval 63.0 to 216.0
118 cell/mm^3
Interval 33.0 to 203.0
Change in CD4+ T-cell Count From Study Entry to Weeks 24, 48, 96 and 144
Change from study entry to week 48
209 cell/mm^3
Interval 138.0 to 319.0
191 cell/mm^3
Interval 89.0 to 311.0
194 cell/mm^3
Interval 76.0 to 276.0
Change in CD4+ T-cell Count From Study Entry to Weeks 24, 48, 96 and 144
Change from study entry to week 96
280 cell/mm^3
Interval 180.0 to 390.0
247 cell/mm^3
Interval 107.0 to 343.0
248 cell/mm^3
Interval 124.0 to 341.0
Change in CD4+ T-cell Count From Study Entry to Weeks 24, 48, 96 and 144
Change from study entry to week 144
305 cell/mm^3
Interval 209.0 to 426.0
279 cell/mm^3
Interval 142.0 to 400.0
227 cell/mm^3
Interval 115.0 to 391.0

SECONDARY outcome

Timeframe: Study entry, weeks 4, 24, 48 and 96

Population: Intention to treat; all eligible participants with available data were included. Participants were analyzed per original assigned randomized treatment and stratification in ACTG A5257.

Total cholesterol (TC, unit of measure mg/dL) was measured at study entry and weeks 4, 24, 48 and 96 from participants who reported fasting for at least 8 hours prior to assessment; all results were centrally laboratory tested in batch. Change in TC was calculated as (week 4, 24, 48 or 96 result) - (study entry result).

Outcome measures

Outcome measures
Measure
Cohort A: ATV/RTV + FTC/TDF
n=109 Participants
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
n=105 Participants
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
n=112 Participants
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)
Change in Fasting Total Cholesterol (TC) From Study Entry to Weeks 4, 24, 48 and 96
Change from study entry to week 24
9 mg/dL
Interval -8.0 to 24.0
-4 mg/dL
Interval -23.0 to 14.0
7 mg/dL
Interval -6.0 to 33.0
Change in Fasting Total Cholesterol (TC) From Study Entry to Weeks 4, 24, 48 and 96
Change from study entry to week 48
8 mg/dL
Interval -8.0 to 26.0
-1 mg/dL
Interval -24.0 to 24.0
12 mg/dL
Interval -7.0 to 31.0
Change in Fasting Total Cholesterol (TC) From Study Entry to Weeks 4, 24, 48 and 96
Change from study entry to week 96
12 mg/dL
Interval -6.0 to 32.0
1 mg/dL
Interval -16.0 to 23.0
14 mg/dL
Interval -8.0 to 38.0
Change in Fasting Total Cholesterol (TC) From Study Entry to Weeks 4, 24, 48 and 96
Change from study entry to week 4
4 mg/dL
Interval -11.0 to 19.0
-7 mg/dL
Interval -25.0 to 9.0
3 mg/dL
Interval -13.0 to 21.0

SECONDARY outcome

Timeframe: Study entry, weeks 4, 24, 48 and 96

Population: Intention to treat; all eligible participants with available data were included. Participants were analyzed per original assigned randomized treatment and stratification in ACTG A5257.

Triglyceride (TG, unit of measure mg/dL) was measured at study entry and weeks 4, 24, 48 and 96 from participants who reported fasting for at least 8 hours prior to assessment; all results were centrally laboratory tested in batch. Change in TG was calculated as (week 4, 24, 48 or 96 result) - (study entry result).

Outcome measures

Outcome measures
Measure
Cohort A: ATV/RTV + FTC/TDF
n=109 Participants
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
n=105 Participants
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
n=112 Participants
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)
Change in Fasting Triglyceride (TG) From Study Entry to Weeks 4, 24, 48 and 96
Change from study entry to week 24
6 mg/dL
Interval -20.0 to 39.0
-16 mg/dL
Interval -48.0 to 4.0
2 mg/dL
Interval -19.0 to 46.0
Change in Fasting Triglyceride (TG) From Study Entry to Weeks 4, 24, 48 and 96
Change from study entry to week 48
9 mg/dL
Interval -22.0 to 50.0
-13 mg/dL
Interval -40.0 to 13.0
8 mg/dL
Interval -18.0 to 41.0
Change in Fasting Triglyceride (TG) From Study Entry to Weeks 4, 24, 48 and 96
Change from study entry to week 96
10 mg/dL
Interval -29.0 to 45.0
-7 mg/dL
Interval -28.0 to 19.0
0 mg/dL
Interval -27.0 to 28.0
Change in Fasting Triglyceride (TG) From Study Entry to Weeks 4, 24, 48 and 96
Change from study entry to week 4
14 mg/dL
Interval -19.0 to 50.0
-12 mg/dL
Interval -41.0 to 11.0
15 mg/dL
Interval -7.0 to 43.0

SECONDARY outcome

Timeframe: Study entry, weeks 4, 24, 48 and 96

Population: Intention to treat; all eligible participants with available data were included. Participants were analyzed per original assigned randomized treatment and stratification in ACTG A5257.

HDL cholesterol (unit of measure mg/dL) was measured at study entry and weeks 4, 24, 48 and 96 from participants who reported fasting for at least 8 hours prior to assessment; all results were centrally laboratory tested in batch. Change in HDL-C was calculated as (week 4, 24, 48 or 96 result) - (study entry result).

Outcome measures

Outcome measures
Measure
Cohort A: ATV/RTV + FTC/TDF
n=109 Participants
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
n=105 Participants
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
n=112 Participants
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)
Change in Fasting High-density Lipoprotein Cholesterol (HDL-C) From Study Entry to Weeks 4, 24, 48 and 96
Change from study entry to week 48
2 mg/dL
Interval -5.0 to 10.0
2 mg/dL
Interval -3.0 to 10.0
1 mg/dL
Interval -3.0 to 6.0
Change in Fasting High-density Lipoprotein Cholesterol (HDL-C) From Study Entry to Weeks 4, 24, 48 and 96
Change from study entry to week 96
4 mg/dL
Interval -3.0 to 10.0
4 mg/dL
Interval -2.0 to 10.0
4 mg/dL
Interval -3.0 to 9.0
Change in Fasting High-density Lipoprotein Cholesterol (HDL-C) From Study Entry to Weeks 4, 24, 48 and 96
Change from study entry to week 4
-1 mg/dL
Interval -6.0 to 6.0
-2 mg/dL
Interval -6.0 to 4.0
-3 mg/dL
Interval -7.0 to 2.0
Change in Fasting High-density Lipoprotein Cholesterol (HDL-C) From Study Entry to Weeks 4, 24, 48 and 96
Change from study entry to week 24
3 mg/dL
Interval -3.0 to 10.0
3 mg/dL
Interval -4.0 to 7.0
0 mg/dL
Interval -5.0 to 9.0

SECONDARY outcome

Timeframe: Study entry, weeks 4, 24, 48 and 96

Population: Intention to treat; all eligible participants with available data were included. Participants were analyzed per original assigned randomized treatment and stratification in ACTG A5257.

Calculated LDL-C (unit of measure mg/dL) was measured at study entry and weeks 4, 24, 48 and 96 from participants who reported fasting for at least 8 hours prior to assessment; all results were centrally laboratory tested in batch. Change in calculated LDL-C was calculated as (week 4, 24, 48 or 96 result) - (study entry result).

Outcome measures

Outcome measures
Measure
Cohort A: ATV/RTV + FTC/TDF
n=108 Participants
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
n=104 Participants
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
n=110 Participants
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)
Change in Fasting Calculated Low-density Lipoprotein Cholesterol (LDL-C) From Study Entry to Weeks 4, 24, 48 and 96
Change from study entry to week 4
0 mg/dL
Interval -12.0 to 11.0
-3 mg/dL
Interval -17.0 to 10.0
1 mg/dL
Interval -6.0 to 17.0
Change in Fasting Calculated Low-density Lipoprotein Cholesterol (LDL-C) From Study Entry to Weeks 4, 24, 48 and 96
Change from study entry to week 24
2 mg/dL
Interval -15.0 to 16.0
-2 mg/dL
Interval -16.0 to 14.0
3 mg/dL
Interval -8.0 to 24.0
Change in Fasting Calculated Low-density Lipoprotein Cholesterol (LDL-C) From Study Entry to Weeks 4, 24, 48 and 96
Change from study entry to week 48
1 mg/dL
Interval -12.0 to 17.0
-1 mg/dL
Interval -16.0 to 21.0
5 mg/dL
Interval -8.0 to 19.0
Change in Fasting Calculated Low-density Lipoprotein Cholesterol (LDL-C) From Study Entry to Weeks 4, 24, 48 and 96
Change from study entry to week 96
2 mg/dL
Interval -11.0 to 20.0
-1 mg/dL
Interval -15.0 to 18.0
6 mg/dL
Interval -8.0 to 31.0

SECONDARY outcome

Timeframe: Study entry, weeks 4, 24, 48 and 96

Population: Intention to treat; all eligible participants with available data were included. Participants were analyzed per original assigned randomized treatment and stratification in ACTG A5257.

Glucose (unit of measure mg/dL) was measured at study entry and weeks 4, 24, 48 and 96; all results reflect measures captured from participants who reported fasting for at least 8 hours prior to assessment. Change was calculated as (fasting result during at week 4, 24, 48 or 96) - (fasting result at study entry).

Outcome measures

Outcome measures
Measure
Cohort A: ATV/RTV + FTC/TDF
n=109 Participants
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
n=105 Participants
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
n=112 Participants
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)
Change in Fasting Glucose Level From Study Entry to Weeks 4, 24, 48 and 96
Change from study entry to week 96
3 mg/dL
Interval -2.0 to 10.0
6 mg/dL
Interval 2.0 to 13.0
2 mg/dL
Interval -2.0 to 8.0
Change in Fasting Glucose Level From Study Entry to Weeks 4, 24, 48 and 96
Change from study entry to week 4
3 mg/dL
Interval -2.0 to 8.0
3 mg/dL
Interval -2.0 to 8.0
2 mg/dL
Interval -3.0 to 7.0
Change in Fasting Glucose Level From Study Entry to Weeks 4, 24, 48 and 96
Change from study entry to week 24
4 mg/dL
Interval -1.0 to 8.0
4 mg/dL
Interval 0.0 to 10.0
4 mg/dL
Interval -3.0 to 8.0
Change in Fasting Glucose Level From Study Entry to Weeks 4, 24, 48 and 96
Change from study entry to week 48
4 mg/dL
Interval -2.0 to 14.0
4 mg/dL
Interval -2.0 to 10.0
2 mg/dL
Interval -5.0 to 7.0

SECONDARY outcome

Timeframe: Study entry, weeks 4, 24, 48 and 96

Population: Intention to treat; all eligible participants with available data were included. Participants were analyzed per original assigned randomized treatment and stratification in ACTG A5257.

Insulin (unit of measure uIU/dL) was measured at study entry and weeks 4, 24, 48 and 96; all results reflect measures captured from participants who reported fasting for at least 8 hours prior to assessment. Change was calculated as (fasting result during at week 4, 24, 48 or 96) - (fasting result at study entry).

Outcome measures

Outcome measures
Measure
Cohort A: ATV/RTV + FTC/TDF
n=109 Participants
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
n=105 Participants
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
n=112 Participants
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)
Change in Fasting Insulin Level From Study Entry to Weeks 4, 24, 48 and 96
Change from study entry to week 4
4.0 uIU/dL
Interval 1.0 to 8.0
3.0 uIU/dL
Interval 0.0 to 6.0
3.0 uIU/dL
Interval 0.0 to 5.0
Change in Fasting Insulin Level From Study Entry to Weeks 4, 24, 48 and 96
Change from study entry to week 24
4.0 uIU/dL
Interval 1.0 to 8.0
3.0 uIU/dL
Interval 1.0 to 5.0
2.0 uIU/dL
Interval 0.0 to 6.0
Change in Fasting Insulin Level From Study Entry to Weeks 4, 24, 48 and 96
Change from study entry to week 48
4.0 uIU/dL
Interval 0.0 to 9.0
3.0 uIU/dL
Interval 0.0 to 7.0
3.0 uIU/dL
Interval 0.0 to 5.0
Change in Fasting Insulin Level From Study Entry to Weeks 4, 24, 48 and 96
Change from study entry to week 96
3.5 uIU/dL
Interval 0.0 to 8.0
3.0 uIU/dL
Interval 0.0 to 6.0
2.0 uIU/dL
Interval 0.0 to 6.0

SECONDARY outcome

Timeframe: Study entry, weeks 48 and 96

Population: Intention to treat; all eligible participants with available data were included. Participants were analyzed per original assigned randomized treatment and stratification in ACTG A5257.

D-dimer was measured at study entry and weeks 48 and 96 (unit of measure ug/ml). Fold change from study entry to week 48 or week 96 was calculated as (week 48 value or week 96 value) / (study entry value). Results identified above or below the limit of quantification were imputed at the quantification limit of the respective assay.

Outcome measures

Outcome measures
Measure
Cohort A: ATV/RTV + FTC/TDF
n=108 Participants
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
n=105 Participants
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
n=110 Participants
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)
Fold Change in D-dimer From Study Entry to Weeks 48 and 96
Fold change from study entry to week 96
0.52 Fold change
Interval 0.26 to 1.0
0.72 Fold change
Interval 0.44 to 1.15
0.65 Fold change
Interval 0.29 to 1.53
Fold Change in D-dimer From Study Entry to Weeks 48 and 96
Fold change from study entry to week 48
0.57 Fold change
Interval 0.31 to 1.0
0.73 Fold change
Interval 0.4 to 1.43
0.65 Fold change
Interval 0.35 to 1.0

SECONDARY outcome

Timeframe: Study entry, weeks 48 and 96

Population: Intention to treat; all eligible participants with available data were included. Participants were analyzed per original assigned randomized treatment and stratification in ACTG A5257.

hsCRP was measured at study entry and weeks 48 and 96 (unit of measure ug/ml). Fold change from study entry to week 48 or week 96 was calculated as (week 48 value or week 96 value) / (study entry value). Results identified above or below the limit of quantification were imputed at the quantification limit of the respective assay.

Outcome measures

Outcome measures
Measure
Cohort A: ATV/RTV + FTC/TDF
n=109 Participants
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
n=106 Participants
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
n=109 Participants
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)
Fold Change in High Sensitivity C-reactive Protein (hsCRP) From Study Entry to Weeks 48 and 96
Fold change from study entry to week 48
0.75 Fold change
Interval 0.44 to 1.54
0.88 Fold change
Interval 0.4 to 1.75
0.78 Fold change
Interval 0.32 to 1.54
Fold Change in High Sensitivity C-reactive Protein (hsCRP) From Study Entry to Weeks 48 and 96
Fold change from study entry to week 96
0.85 Fold change
Interval 0.45 to 1.64
0.78 Fold change
Interval 0.32 to 1.54
1.31 Fold change
Interval 0.65 to 2.6

SECONDARY outcome

Timeframe: Study entry, weeks 48 and 96

Population: Intention to treat; all eligible participants with available data were included. Participants were analyzed per original assigned randomized treatment and stratification in ACTG A5257.

IL-6 was measured at study entry and weeks 48 and 96 (unit of measure pg/ml). Fold change from study entry to week 48 or week 96 was calculated as (week 48 value or week 96 value) / (study entry value). Results identified above or below the limit of quantification were imputed at the quantification limit of the respective assay.

Outcome measures

Outcome measures
Measure
Cohort A: ATV/RTV + FTC/TDF
n=109 Participants
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
n=106 Participants
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
n=109 Participants
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)
Fold Change in Interleukin-6 (IL-6) From Study Entry to Weeks 48 and 96
Fold change from study entry to week 96
0.89 Fold change
Interval 0.56 to 1.45
0.82 Fold change
Interval 0.51 to 1.34
0.89 Fold change
Interval 0.58 to 1.65
Fold Change in Interleukin-6 (IL-6) From Study Entry to Weeks 48 and 96
Fold change from study entry to week 48
0.62 Fold change
Interval 0.39 to 1.16
0.71 Fold change
Interval 0.51 to 1.23
0.75 Fold change
Interval 0.46 to 1.37

SECONDARY outcome

Timeframe: Study entry, weeks 48 and 96

Population: Intention to treat; all eligible participants with available data were included. Participants were analyzed per original assigned randomized treatment and stratification in ACTG A5257.

Soluble CD14 was measured at study entry and weeks 48 and 96 (unit of measure ng/ml). Fold change from study entry to week 48 or week 96 was calculated as (week 48 value or week 96 value) / (study entry value). Results identified above or below the limit of quantification were imputed at the quantification limit of the respective assay.

Outcome measures

Outcome measures
Measure
Cohort A: ATV/RTV + FTC/TDF
n=108 Participants
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
n=106 Participants
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
n=108 Participants
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)
Fold Change in Soluble CD14 From Study Entry to Weeks 48 and 96
Fold change from study entry to week 48
1.01 Fold change
Interval 0.9 to 1.14
0.91 Fold change
Interval 0.78 to 1.07
1.00 Fold change
Interval 0.83 to 1.13
Fold Change in Soluble CD14 From Study Entry to Weeks 48 and 96
Fold change from study entry to week 96
0.98 Fold change
Interval 0.83 to 1.18
0.90 Fold change
Interval 0.76 to 1.02
0.98 Fold change
Interval 0.79 to 1.17

SECONDARY outcome

Timeframe: Study entry, weeks 48 and 96

Population: Intention to treat; all eligible participants with available data were included. Participants were analyzed per original assigned randomized treatment and stratification in ACTG A5257.

Soluble CD163 was measured at study entry and weeks 48 and 96 (unit of measure ng/ml). Fold change from study entry to week 48 or week 96 was calculated as (week 48 value or week 96 value) / (study entry value). Results identified above or below the limit of quantification were imputed at the quantification limit of the respective assay.

Outcome measures

Outcome measures
Measure
Cohort A: ATV/RTV + FTC/TDF
n=104 Participants
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
n=101 Participants
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
n=102 Participants
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)
Fold Change in Soluble CD163 From Study Entry to Weeks 48 and 96
Fold change from study entry to week 48
0.54 Fold change
Interval 0.44 to 0.71
0.62 Fold change
Interval 0.48 to 0.78
0.61 Fold change
Interval 0.49 to 0.78
Fold Change in Soluble CD163 From Study Entry to Weeks 48 and 96
Fold change from study entry to week 96
0.51 Fold change
Interval 0.4 to 0.66
0.56 Fold change
Interval 0.43 to 0.72
0.58 Fold change
Interval 0.44 to 0.8

SECONDARY outcome

Timeframe: Study entry, weeks 24 and 96

Population: Intention to treat; all eligible participants with available data were included. Participants were analyzed per original assigned randomized treatment and stratification in ACTG A5257.

Percent expression of CD38+HLADR+ on CD4+ was measured at study entry and weeks 24 and 96 (unit of measure percent). Fold change from study entry to week 24 or week 96 was calculated as (week 24 value or week 96 value) / (study entry value).

Outcome measures

Outcome measures
Measure
Cohort A: ATV/RTV + FTC/TDF
n=101 Participants
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
n=95 Participants
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
n=101 Participants
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)
Fold Change in Percent Expression of CD38+HLADR+ on CD4+ (Percent) From Study Entry to Weeks 24 and 96
Fold change from study entry to week 96
0.38 Fold change
Interval 0.24 to 0.55
0.34 Fold change
Interval 0.23 to 0.54
0.37 Fold change
Interval 0.25 to 0.56
Fold Change in Percent Expression of CD38+HLADR+ on CD4+ (Percent) From Study Entry to Weeks 24 and 96
Fold change from study entry to week 24
0.49 Fold change
Interval 0.35 to 0.7
0.51 Fold change
Interval 0.37 to 0.68
0.52 Fold change
Interval 0.4 to 0.79

SECONDARY outcome

Timeframe: Study entry, weeks 24 and 96

Population: Intention to treat; all eligible participants with available data were included. Participants were analyzed per original assigned randomized treatment and stratification in ACTG A5257.

Percent expression of CD38+HLADR+ on CD8+ was measured at study entry and weeks 24 and 96 (unit of measure percent). Fold change from study entry to week 24 or week 96 was calculated as (week 24 value or week 96 value) / (study entry value).

Outcome measures

Outcome measures
Measure
Cohort A: ATV/RTV + FTC/TDF
n=101 Participants
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
n=95 Participants
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
n=101 Participants
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)
Fold Change in Percent Expression of CD38+HLADR+ on CD8+ (Percent) From Study Entry to Weeks 24 and 96
Fold change from study entry to week 24
0.51 Fold change
Interval 0.39 to 0.63
0.56 Fold change
Interval 0.46 to 0.71
0.59 Fold change
Interval 0.39 to 0.74
Fold Change in Percent Expression of CD38+HLADR+ on CD8+ (Percent) From Study Entry to Weeks 24 and 96
Fold change from study entry to week 96
0.35 Fold change
Interval 0.27 to 0.5
0.36 Fold change
Interval 0.24 to 0.46
0.38 Fold change
Interval 0.22 to 0.56

Adverse Events

Cohort A: ATV/RTV + FTC/TDF

Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths

Cohort B: RAL + FTC/TDF

Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths

Cohort C: DRV/RTV + FTC/TDF

Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

ACTG Clinicaltrials.gov Coordinator

ACTG Network Coordinating Center, Social and Scientific Systems, Inc.

Phone: (301) 628-3313

Results disclosure agreements

  • Principal investigator is a sponsor employee In accordance with the Clinical Trials Agreement between NIAID (DAIDS) and company collaborators, NIAID (DAIDS) provides companies with a copy of any abstract, press release, or manuscript prior to submission for publication with sufficient time for company review and comment. The publication/other disclosure can be delayed for up to 30 additional business days for manuscripts and five (5) business days for abstracts, to preserve U.S. or foreign patent or other intellectual property rights.
  • Publication restrictions are in place

Restriction type: OTHER