Bone, Immunologic, and Virologic Effects of a Antiretroviral Regimen

• Sponsor: AIDS Clinical Trials Group (Other)
• Overall Status: Completed
• CT.gov ID: NCT01400412
• Collaborator: National Institute of Allergy and Infectious Diseases (NIAID) (NIH)
• Enrollment: 262
• Locations: 38
• Arms: 2
• Actual Duration (Months): 28.5
• Patients Per Site: 6.9
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The main purpose of this study was to compare the effects on bones of the following two drug combinations:

• maraviroc (MVC), emtricitabine (FTC), plus darunavir/ritonavir (DRV/r)

• tenofovir (TDF) plus emtricitabine (FTC) plus darunavir/ritonavir (DRV/r)

Additional study objectives were the following:

• To see how the drug combinations affect the brain and kidneys.

• To see how well the drug combinations lower the HIV viral load.

• To see how safe the drug combinations are, how well people are able to take the study drug combinations, and how well their immune systems respond to the study drugs.

Condition or Disease	Intervention/Treatment	Phase
HIV-1 Infection	Drug: Darunavir; Drug: Ritonavir; Drug: Tenofovir disoproxil fumarate; Drug: Emtricitabine; Drug: Placebo for Tenofovir disoproxil fumarate; Drug: Placebo for Maraviroc; Drug: Maraviroc	Phase 2

Detailed Description

There are now several HIV treatment options for a person with HIV infection who has not yet been treated. Most people who receive treatment and take their medications as directed have a good result. This is usually determined by measuring the amount of HIV in the blood (viral load). The best response is when HIV cannot be found (less than 50 copies/mL) in the blood. However, it has recently become clear that some people with HIV who are receiving effective HIV drugs continue to have more health problems than people without HIV infection. Sometimes, there is damage to organs in the body, including bone, kidneys, and the brain.

Study Design

• Study Type: Interventional
• Actual Enrollment: 262 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Phase 2b, Double-Blind, Placebo-Controlled, Exploratory Randomized Trial to Determine the Bone, Immunologic, Virologic, and Neurocognitive Effects of a Novel Maraviroc-Containing Antiretroviral Regimen in Treatment-Naïve Patients Infected With R5-Tropic HIV-1
• Actual Study Start Date: Jan 17, 2012
• Actual Primary Completion Date: Jun 1, 2014
• Actual Study Completion Date: Jun 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: MVC Arm: DRV/r + MVC + FTC + TDF placebo Darunavir 800 mg PO QD + Ritonavir 100 mg PO QD + Maraviroc 150 mg PO QD + Emtricitabine 200 mg PO QD + Placebo for Tenofovir disoproxil fumarate PO QD	Drug: Darunavir; Darunavir was administered orally once a day as two 400 mg tablets with food. When the 800 mg formulation tablet became available, it was substituted for the two 400 mg tablet.; Other Names: Prezista TMC-114 DRV ; Drug: Ritonavir; Ritonavir was administered orally together with darunavir as one 100 mg tablet once daily with food.; Other Names: Norvir RTV ; Drug: Emtricitabine; Emtricitabine was administered orally once a day as one 200 mg capsule.; Other Names: Emtriva FTC Coviracil ; Drug: Placebo for Tenofovir disoproxil fumarate; Placebo for tenofovir disoproxil fumarate was administered orally once a day as one tablet.; Drug: Maraviroc; Maraviroc was administered orally once a day as one 150 mg tablet.; Other Names: Celesentri Selzentry
Experimental: TDF Arm: DRV/r + TDF + FTC + MVC placebo Darunavir 800 mg PO QD + Ritonavir 100 mg PO QD + Emtricitabine 200 mg PO QD + Tenofovir disoproxil fumarate 300 mg PO QD + Placebo for Maraviroc PO QD	Drug: Darunavir; Darunavir was administered orally once a day as two 400 mg tablets with food. When the 800 mg formulation tablet became available, it was substituted for the two 400 mg tablet.; Other Names: Prezista TMC-114 DRV ; Drug: Ritonavir; Ritonavir was administered orally together with darunavir as one 100 mg tablet once daily with food.; Other Names: Norvir RTV ; Drug: Tenofovir disoproxil fumarate; Tenofovir disoproxil fumarate was administered orally as one 300 mg tablet once a day.; Other Names: Viread TDF ; Drug: Emtricitabine; Emtricitabine was administered orally once a day as one 200 mg capsule.; Other Names: Emtriva FTC Coviracil ; Drug: Placebo for Maraviroc; Placebo for maraviroc was administered orally once a day as one tablet.

Outcome Measures

Primary Outcome Measures

1. Percent Change From Baseline in Total Hip Bone Mineral Density (BMD) [Week 0, week 48]

   The primary endpoint is the percent change in bone mineral density (BMD) at total hip (as measured by DXA scan) from baseline (week 0) to week 48.

Secondary Outcome Measures

1. Percent Change in Lumbar Spine Bone Mineral Density (BMD) [Week 0, week 48]

   The percent change in bone mineral density (BMD) at lumbar spine (as measured by DXA scan) from baseline (week 0) to week 48.

2. Change in CD4 Count From Baseline to Week 24 [Week 0, week 24]

   Change in CD4 count from baseline (week 0) to week 24

3. Change in CD4 Count From Baseline to Week 48 [Week 0, week 48]

   Change in CD4 count from baseline (week 0) to week 48

4. CD8+ T-cell Change From Baseline to Week 48 [At weeks 0 and 48]

   CD8+ T-cell change from baseline to week 48

5. Percentage Change in Expression of CD38+/HLA-DR+ on CD4+ T Cells From Baseline to Week 48 [At weeks 0 and 48]

   percentage change is define as [ (week 48 - week 0) / week 0 ] * 100%

6. Percentage Change in Expression of CD38+/HLA-DR+ on CD8+ T Cells From Baseline to Week 48 [At weeks 0 and 48]

   percentage change is defined as [ (week 48 - week 0) / week 0 ] * 100%

7. Percent Change in Expression of CD28+/CD57+ on CD8+ T Cells From Baseline to Week 48 [At weeks 0 and 48]

   percentage change is define as [ (week 48 - week 0) / week 0 ] * 100%

8. Percent Change in Expression of CD57+ on CD8+ T Cells From Baseline to Week 48 [At weeks 0 and 48]

   percentage change is define as [ (week 48 - week 0) / week 0 ] * 100%

9. Percent Change in Expression of CD28+ on CD8+ T Cells From Baseline to Week 48 [At weeks 0 and 48]

   percentage change is define as [ (week 48 - week 0) / week 0 ] * 100%

10. Percent Change in Expression of RANKL+ on CD8+ T Cells From Baseline to Week 48 [At weeks 0 and 48]

    percentage change is defined as [ (week 48 - week 0) / week 0 ] * 100%

11. Change in Levels of IL-6 From Baseline to Week 48 [At weeks 0 and 48]

    Change in levels of Interleukin 6 (IL-6) from baseline to week 48

12. Change in Level of IP-10 From Baseline to Week 48 [At weeks 0 and 48]

    Change in level of Interferon gamma-induced protein 10 (IP-10) from baseline to week 48

13. Change in Levels of sCD163 From Baseline to Week 48 [At weeks 0 and 48]

    Change in levels of soluble CD163 from baseline to week 48

14. Change in Levels of sCD14 From Baseline [At weeks 0 and 48]

    Change in levels of soluble CD14 from baseline

15. Change in Levels of D-dimer From Baseline [At weeks 0 and 48]

    Change in levels of D-dimer from baseline

16. Cumulative Probability of Virologic Failure by Week 48 [From study treatment initiation to week 48]

    Confirmed virologic failure is defined as confirmed plasma HIV-1 RNA levels > 1000 copies/mL at or after week 16 and before week 24, or confirmed HIV-1 RNA levels> 200 copies/mL at or after week 24. Participants who discontinued the study with an unconfirmed virologic failure (HIV-1 RNA > 1000 copies at 16 weeks or HIV-1 RNA level > 200 copies/mL at or after week 24) are considered as virologic failures at the study visit week of the unconfirmed value. Time to virologic failure is defined as the time from study entry to the planned visit week of the initial failure. Product-limit estimates for the survival function were used to estimate the cumulative probability of virologic failure over time and its corresponding 95% confidence interval for each treatment group.

17. Number of Participants Who Experienced Bone Fractures [From study treatment initiation to week 48]

    Number of participants who experienced bone fractures during the study

18. Number of Participants Who Died During the Study [From study treatment initiation to week 48]

    Number of participants who died during the study

19. Number of Participants Who Developed Grade 3 or 4 Primary Adverse Events [From study treatment initiation to week 48]

    Grade 3 or 4 primary adverse events includes primary signs/symptoms, primary laboratory abnormalities, or primary diagnoses. See DAIDS AE Grading Table Version 1.0, Dec 2004 (Clarification, Aug 2009)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• HIV-1 infection

• No evidence of exclusionary resistance mutations defined as evidence of any major NRTI mutation according to the current IAS list of HIV-1 Resistance Mutations Associated with Drug Resistance, or any DRV RAMs (refer to the A5303 PSWP for a list of these mutations) on any genotype; or evidence of significant NRTI or DRV resistance on any phenotype performed at any time prior to study entry. NNRTI-associated resistance mutations were not exclusionary.

• ARV drug-naïve, defined as </=10 days of ART at any time prior to study entry, except in the instances defined in section 4.1.3 of the protocol.

• R5-only tropism based on Trofile testing performed within 90 days prior to study entry.

• Screening HIV-1 RNA >1000 copies/mL obtained within 90 days prior to study entry by any FDA-approved test for quantifying HIV-1 RNA at any laboratory that has a CLIA certification or its equivalent.

• Known hepatitis C virus (HCV) antibody status (performed at any laboratory that had a CLIA certification or its equivalent).

• Certain laboratory values obtained within 60 days prior to study entry, as defined in section 4.1.7 of the protocol.

• For women of reproductive potential, negative serum or urine pregnancy test with a sensitivity of ≤25 mIU/mL within 72 hours prior to study entry.

• Female subjects of reproductive potential, who were participating in sexual activity that could lead to pregnancy, must agree to use at least one reliable method of contraception (as defined in section 4.1.9.1 of the protocol) while receiving the study drugs and for 6 weeks after stopping the medications.

• Female subjects who were not of reproductive potential or whose male partner(s) had azoospermia were eligible to take study drugs without the use of contraceptives.

• Ability and willingness of subject or legal guardian/representative to give written informed consent.

• Willingness to undergo neuropsychological testing.

• DXA scan performed after confirmation of the subject's eligibility by Trofile testing but no more than 4 weeks prior to randomization.

Exclusion Criteria:

• Use of immunomodulators (e.g., interleukins, interferons, cyclosporine), HIV vaccine, systemic cytotoxic chemotherapy, or investigational therapy within 30 days prior to study entry.

• New use of hormonal therapies within 6 months prior to study entry. (Stable therapy for ≥6 months was permitted.)

• New use of oral contraceptive pills (OCPs) in the past 3 months. (Stable therapy for ≥3 months was permitted.)

• Any oral, intravenous, or inhaled steroids within 30 days prior to study entry. (Intranasal steroids and topical corticosteroids were allowed.)

• Known allergy/sensitivity to study drugs or their formulations. (A history of sulfa allergy was not an exclusionary condition.)

• Known hypersensitivity to soy lecithin.

• Serious illness requiring systemic treatment and/or hospitalization until subject either completes therapy or was clinically stable on therapy, in the opinion of the site investigator, for at least 7 days prior to study entry. (Oral candidiasis, vaginal candidiasis, mucocutaneous herpes simplex, and other minor illnesses (as judged by the site investigator) were not exclusionary conditions.)

• Requirement for any current medications that were prohibited with any study drugs. (Prohibited medications must be discontinued at least 30 days prior to entry. Refer to the A5303 PSWP for a list of prohibited medications.)

• The presence of decompensated cirrhosis.

• A history of or current, active HBV infection defined as positive hepatitis B surface antigen test (or positive HBV DNA in subjects with isolated HBcAb positivity, defined as negative HBsAg, negative HBsAb, and positive HBcAb) at screening.

• Current or prior use of biphosphonates, teriparatide, raloxifene, or denosumab.

• Weight >300 lbs (exceeds weight limit of DXA scanners).

• History after 18 years of age of fracture of the spine, hip, wrist, or other site thought to be related to osteoporosis or bone fragility.

• Currently breastfeeding.

• Any active psychiatric illness including schizophrenia, severe depression, or severe bipolar affective disorder that, in the opinion of the investigator, could confound the analysis of the neurological examination or neuropsychological test results.

• Active drug or alcohol abuse that, in the investigator's opinion, could prevent compliance with study procedures or confound the analysis of study endpoints.

• Active brain infection (except for HIV-1), fungal meningitis, toxoplasmosis, central nervous system (CNS) lymphoma, brain neoplasm, or space-occupying brain lesion requiring acute or chronic therapy.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	31788 Alabama CRS	Birmingham	Alabama	United States	35294
2	University of Southern California (1201)	Los Angeles	California	United States	90033-1079
3	UCLA CARE Center CRS (601)	Los Angeles	California	United States	90095
4	Ucsd, Avrc Crs (701)	San Diego	California	United States	92103
5	Ucsf Aids Crs (801)	San Francisco	California	United States	94110
6	University of Colorado Hospital CRS (6101)	Aurora	Colorado	United States	80045
7	University of Colorado Denver ATN CRS (33022)	Denver	Colorado	United States	80262
8	Georgetown University CRS (GU CRS) (1008)	Washington	District of Columbia	United States	20007
9	Children's National Med. Ctr. ATN CRS (33003)	Washington	District of Columbia	United States	20010
10	Univ. of Miami AIDS CRS (901)	Miami	Florida	United States	33136
11	Univ. of South Florida (USF) College of Medicine ATN CRS (33001)	Tampa	Florida	United States	33606
12	The Ponce de Leon Center CRS (5802)	Atlanta	Georgia	United States	30308
13	Northwestern University CRS (2701)	Chicago	Illinois	United States	60611
14	Rush Univ. Med. Ctr. ACTG CRS (2702)	Chicago	Illinois	United States	60612
15	IHV Baltimore Treatment CRS (4651)	Baltimore	Maryland	United States	21201
16	201 Johns Hopkins University CRS	Baltimore	Maryland	United States	21205
17	Massachusetts General Hospital ACTG CRS (101)	Boston	Massachusetts	United States	02114
18	Brigham and Women's Hosp. ACTG CRS (107)	Boston	Massachusetts	United States	02115
19	Washington U CRS (2101)	Saint Louis	Missouri	United States	63110
20	Cooper Univ. Hosp. CRS (31476)	Camden	New Jersey	United States	08103
21	Columbia Physicians and Surgeons CRS (30329)	New York	New York	United States	10032
22	Trillium Health ACTG CRS (1108)	Rochester	New York	United States	14642
23	University of Rochester Adult HIV Therapeutic Strategies Network CRS (31787)	Rochester	New York	United States	14642
24	Unc Aids Crs (3201)	Chapel Hill	North Carolina	United States	27516
25	Moses H. Cone Memorial Hospital CRS (3203)	Greensboro	North Carolina	United States	27401
26	Univ. of Cincinnati CRS (2401)	Cincinnati	Ohio	United States	45267
27	Case CRS (2501)	Cleveland	Ohio	United States	44106
28	Metro Health CRS (2503)	Cleveland	Ohio	United States	44109
29	The Ohio State Univ. AIDS CRS (2301)	Columbus	Ohio	United States	43210
30	Hops. of Univ. of Pennsylvania CRS (6201)	Philadelphia	Pennsylvania	United States	19104
31	The Miriam Hospital ACTG CRS (2951)	Providence	Rhode Island	United States	02906
32	St. Jude Children's Research Hosp. ATN CRS (33016)	Memphis	Tennessee	United States	38105
33	Vanderbilt Therapeutics CRS (3652)	Nashville	Tennessee	United States	37232
34	Peabody Health Center CRS (31443)	Dallas	Texas	United States	75215
35	Houston AIDS Research Team CRS (31473)	Houston	Texas	United States	77030
36	Texas Childrens Hospital ATN CRS (33018)	Houston	Texas	United States	77030
37	University of Washington AIDS CRS (1401)	Seattle	Washington	United States	98104
38	Puerto Rico-AIDS CRS (5401)	San Juan		Puerto Rico	00935

Sponsors and Collaborators

• AIDS Clinical Trials Group
• National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

• Study Chair: Babafemi Taiwo, MBBS, MD, Northwestern University CRS

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: AIDS Clinical Trials Group
• ClinicalTrials.gov Identifier: NCT01400412
• Other Study ID Numbers: ACTG A5303; 1U01AI068636
• First Posted: Jul 22, 2011
• Last Update Posted: Aug 3, 2021
• Last Verified: Jan 1, 2018

• Additional relevant MeSH terms: Ritonavir; Darunavir; Tenofovir; Emtricitabine; Maraviroc

Study Results

Participant Flow

Recruitment Details	A5303 opened under version 1.0 on 12/4/11, and the first participant was enrolled on 1/17/12. Accrual to the study closed on 6/12/13, with a total of 262 participants enrolled at 38 sites

Arm/Group Title	MVC Arm (DRV/r + MVC + FTC + TDF Placebo)	TDF Arm (DRV/r + TDF + FTC + MVC Placebo)
Arm/Group Description	Darunavir 800 mg PO QD + Ritonavir 100 mg PO QD + Maraviroc 150 mg PO QD + Emtricitabine 200 mg PO QD + Placebo for Tenofovir disoproxil fumarate PO QD Darunavir: Darunavir was administered orally once a day as two 400 mg tablets with food. When the 800 mg formulation tablet became available, it was substituted for the two 400 mg tablet. Ritonavir: Ritonavir was administered orally together with darunavir as one 100 mg tablet once daily with food. Emtricitabine: Emtricitabine was administered orally once a day as one 200 mg capsule. Placebo for Tenofovir disoproxil fumarate: Placebo for tenofovir disoproxil fumarate was administered orally once a day as one tablet.	Darunavir 800 mg PO QD + Ritonavir 100 mg PO QD + Emtricitabine 200 mg PO QD + Tenofovir disoproxil fumarate 300 mg PO QD + Placebo for Maraviroc PO QD Darunavir: Darunavir was administered orally once a day as two 400 mg tablets with food. When the 800 mg formulation tablet became available, it was substituted for the two 400 mg tablet. Ritonavir: Ritonavir was administered orally together with darunavir as one 100 mg tablet once daily with food. Tenofovir disoproxil fumarate: Tenofovir disoproxil fumarate was administered orally as one 300 mg tablet once a day. Emtricitabine: Emtricitabine was administered orally once a day as one 200 mg capsule. Placebo for Maraviroc: Placebo for maraviroc was administered orally once a day as one 150 mg tablet.
Period Title: Overall Study
STARTED	130	132
COMPLETED	120	115
NOT COMPLETED	10	17

Baseline Characteristics

Arm/Group Title	MVC Arm (DRV/r + MVC + FTC + TDF Placebo)	TDF Arm (DRV/r + TDF + FTC + MVC Placebo)	Total
Arm/Group Description	Darunavir 800 mg PO QD + Ritonavir 100 mg PO QD + Maraviroc 150 mg PO QD + Emtricitabine 200 mg PO QD + Placebo for Tenofovir disoproxil fumarate PO QD Darunavir: Darunavir was administered orally once a day as two 400 mg tablets with food. When the 800 mg formulation tablet became available, it was substituted for the two 400 mg tablet. Ritonavir: Ritonavir was administered orally together with darunavir as one 100 mg tablet once daily with food. Emtricitabine: Emtricitabine was administered orally once a day as one 200 mg capsule. Placebo for Tenofovir disoproxil fumarate: Placebo for tenofovir disoproxil fumarate was administered orally once a day as one tablet.	Darunavir 800 mg PO QD + Ritonavir 100 mg PO QD + Emtricitabine 200 mg PO QD + Tenofovir disoproxil fumarate 300 mg PO QD + Placebo for Maraviroc PO QD Darunavir: Darunavir was administered orally once a day as two 400 mg tablets with food. When the 800 mg formulation tablet became available, it was substituted for the two 400 mg tablet. Ritonavir: Ritonavir was administered orally together with darunavir as one 100 mg tablet once daily with food. Tenofovir disoproxil fumarate: Tenofovir disoproxil fumarate was administered orally as one 300 mg tablet once a day. Emtricitabine: Emtricitabine was administered orally once a day as one 200 mg capsule. Placebo for Maraviroc: Placebo for maraviroc was administered orally once a day as one 150 mg tablet.	Total of all reporting groups
Overall Participants	130	129	259
Age (years) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [years]	33	33	33
Age, Customized (participants) [Number]
18-29 Years	49 37.7%	48 37.2%	97 37.5%
30-39 Years	40 30.8%	41 31.8%	81 31.3%
40-49 Years	26 20%	24 18.6%	50 19.3%
>=50 Years	15 11.5%	16 12.4%	31 12%
Sex: Female, Male (Count of Participants)
Female	15 11.5%	9 7%	24 9.3%
Male	115 88.5%	120 93%	235 90.7%
Race/Ethnicity, Customized (participants) [Number]
White non-Hispanic	57 43.8%	59 45.7%	116 44.8%
Black non-Hispanic	45 34.6%	33 25.6%	78 30.1%
Hispanic (regardless of race)	24 18.5%	34 26.4%	58 22.4%
Asian, Pacific Islander	2 1.5%	1 0.8%	3 1.2%
American Indian, Alaskan Native	0 0%	1 0.8%	1 0.4%
More than one race	2 1.5%	1 0.8%	3 1.2%
Region of Enrollment (participants) [Number]
United States	127 97.7%	127 98.4%	254 98.1%
Puerto Rico	3 2.3%	2 1.6%	5 1.9%
CD4 count (cells/mm^3) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [cells/mm^3]	389	392	390
HIV-1 RNA (log10 copies/mL) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [log10 copies/mL]	4.59	4.47	4.50

Outcome Measures

1. Primary Outcome

Title	Percent Change From Baseline in Total Hip Bone Mineral Density (BMD)
Description	The primary endpoint is the percent change in bone mineral density (BMD) at total hip (as measured by DXA scan) from baseline (week 0) to week 48.
Time Frame	Week 0, week 48

Outcome Measure Data

Analysis Population Description

The primary analysis was as-treated which included only participants with total hip BMD measurements available at both week 0 and week 48 who remained on their randomized MVC or TDF component by the time week 48 measurement was taken without an interruption of treatment of more than 10 weeks.

Arm/Group Title	MVC Arm (DRV/r + MVC + FTC + TDF Placebo)	TDF Arm (DRV/r + TDF + FTC + MVC Placebo)
Arm/Group Description	Darunavir 800 mg PO QD + Ritonavir 100 mg PO QD + Maraviroc 150 mg PO QD + Emtricitabine 200 mg PO QD + Placebo for Tenofovir disoproxil fumarate PO QD Darunavir: Darunavir was administered orally once a day as two 400 mg tablets with food. When the 800 mg formulation tablet became available, it was substituted for the two 400 mg tablet. Ritonavir: Ritonavir was administered orally together with darunavir as one 100 mg tablet once daily with food. Emtricitabine: Emtricitabine was administered orally once a day as one 200 mg capsule. Placebo for Tenofovir disoproxil fumarate: Placebo for tenofovir disoproxil fumarate was administered orally once a day as one tablet.	Darunavir 800 mg PO QD + Ritonavir 100 mg PO QD + Emtricitabine 200 mg PO QD + Tenofovir disoproxil fumarate 300 mg PO QD + Placebo for Maraviroc PO QD Darunavir: Darunavir was administered orally once a day as two 400 mg tablets with food. When the 800 mg formulation tablet became available, it was substituted for the two 400 mg tablet. Ritonavir: Ritonavir was administered orally together with darunavir as one 100 mg tablet once daily with food. Tenofovir disoproxil fumarate: Tenofovir disoproxil fumarate was administered orally as one 300 mg tablet once a day. Emtricitabine: Emtricitabine was administered orally once a day as one 200 mg capsule. Placebo for Maraviroc: Placebo for maraviroc was administered orally once a day as one 150 mg tablet.
Measure Participants	115	109
Median (Inter-Quartile Range) [percentage change]	-1.51	-2.40

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	MVC Arm (DRV/r + MVC + FTC + TDF Placebo), TDF Arm (DRV/r + TDF + FTC + MVC Placebo)
	Comments	The null hypothesis is that there is no difference between the two arms in the percent of total hip BMD change from baseline to week 48
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	Two-sided p-value without adjustment for multiple testing, interpreted at the 5% nominal level of significance
	Method	Wilcoxon (Mann-Whitney)
	Comments	Stratified Wilcoxon rank sum test stratified by age (<30 and >=30 years)

2. Secondary Outcome

Title	Percent Change in Lumbar Spine Bone Mineral Density (BMD)
Description	The percent change in bone mineral density (BMD) at lumbar spine (as measured by DXA scan) from baseline (week 0) to week 48.
Time Frame	Week 0, week 48

Outcome Measure Data

Analysis Population Description

As-treated analysis included only participants with available data at both baseline and week 48 who remained on their randomized MVC or TDF component by the time week 48 DEXA measurement was taken without an interruption of treatment for more than 10 weeks.

Arm/Group Title	MVC Arm (DRV/r + MVC + FTC + TDF Placebo)	TDF Arm (DRV/r + TDF + FTC + MVC Placebo)
Arm/Group Description	Darunavir 800 mg PO QD + Ritonavir 100 mg PO QD + Maraviroc 150 mg PO QD + Emtricitabine 200 mg PO QD + Placebo for Tenofovir disoproxil fumarate PO QD Darunavir: Darunavir was administered orally once a day as two 400 mg tablets with food. When the 800 mg formulation tablet became available, it was substituted for the two 400 mg tablet. Ritonavir: Ritonavir was administered orally together with darunavir as one 100 mg tablet once daily with food. Emtricitabine: Emtricitabine was administered orally once a day as one 200 mg capsule. Placebo for Tenofovir disoproxil fumarate: Placebo for tenofovir disoproxil fumarate was administered orally once a day as one tablet.	Darunavir 800 mg PO QD + Ritonavir 100 mg PO QD + Emtricitabine 200 mg PO QD + Tenofovir disoproxil fumarate 300 mg PO QD + Placebo for Maraviroc PO QD Darunavir: Darunavir was administered orally once a day as two 400 mg tablets with food. When the 800 mg formulation tablet became available, it was substituted for the two 400 mg tablet. Ritonavir: Ritonavir was administered orally together with darunavir as one 100 mg tablet once daily with food. Tenofovir disoproxil fumarate: Tenofovir disoproxil fumarate was administered orally as one 300 mg tablet once a day. Emtricitabine: Emtricitabine was administered orally once a day as one 200 mg capsule. Placebo for Maraviroc: Placebo for maraviroc was administered orally once a day as one 150 mg tablet.
Measure Participants	114	108
Median (Inter-Quartile Range) [percentage change]	-0.88	-2.35

3. Secondary Outcome

Title	Change in CD4 Count From Baseline to Week 24
Description	Change in CD4 count from baseline (week 0) to week 24
Time Frame	Week 0, week 24

Outcome Measure Data

Analysis Population Description

Change in total CD4 count is analyzed in the same as-treated population as in the primary as-treated analysis.

Arm/Group Title	MVC Arm (DRV/r + MVC + FTC + TDF Placebo)	TDF Arm (DRV/r + TDF + FTC + MVC Placebo)
Arm/Group Description	Darunavir 800 mg PO QD + Ritonavir 100 mg PO QD + Maraviroc 150 mg PO QD + Emtricitabine 200 mg PO QD + Placebo for Tenofovir disoproxil fumarate PO QD Darunavir: Darunavir was administered orally once a day as two 400 mg tablets with food. When the 800 mg formulation tablet became available, it was substituted for the two 400 mg tablet. Ritonavir: Ritonavir was administered orally together with darunavir as one 100 mg tablet once daily with food. Emtricitabine: Emtricitabine was administered orally once a day as one 200 mg capsule. Placebo for Tenofovir disoproxil fumarate: Placebo for tenofovir disoproxil fumarate was administered orally once a day as one tablet.	Darunavir 800 mg PO QD + Ritonavir 100 mg PO QD + Emtricitabine 200 mg PO QD + Tenofovir disoproxil fumarate 300 mg PO QD + Placebo for Maraviroc PO QD Darunavir: Darunavir was administered orally once a day as two 400 mg tablets with food. When the 800 mg formulation tablet became available, it was substituted for the two 400 mg tablet. Ritonavir: Ritonavir was administered orally together with darunavir as one 100 mg tablet once daily with food. Tenofovir disoproxil fumarate: Tenofovir disoproxil fumarate was administered orally as one 300 mg tablet once a day. Emtricitabine: Emtricitabine was administered orally once a day as one 200 mg capsule. Placebo for Maraviroc: Placebo for maraviroc was administered orally once a day as one 150 mg tablet.
Measure Participants	115	109
Median (Inter-Quartile Range) [cells/mm^3]	165	127

4. Secondary Outcome

Title	Change in CD4 Count From Baseline to Week 48
Description	Change in CD4 count from baseline (week 0) to week 48
Time Frame	Week 0, week 48

Outcome Measure Data

Analysis Population Description

Change in total CD4 count is analyzed in the same as-treated population as in the primary as-treated analysis.

Arm/Group Title	MVC Arm (DRV/r + MVC + FTC + TDF Placebo)	TDF Arm (DRV/r + TDF + FTC + MVC Placebo)
Arm/Group Description	Darunavir 800 mg PO QD + Ritonavir 100 mg PO QD + Maraviroc 150 mg PO QD + Emtricitabine 200 mg PO QD + Placebo for Tenofovir disoproxil fumarate PO QD Darunavir: Darunavir was administered orally once a day as two 400 mg tablets with food. When the 800 mg formulation tablet became available, it was substituted for the two 400 mg tablet. Ritonavir: Ritonavir was administered orally together with darunavir as one 100 mg tablet once daily with food. Emtricitabine: Emtricitabine was administered orally once a day as one 200 mg capsule. Placebo for Tenofovir disoproxil fumarate: Placebo for tenofovir disoproxil fumarate was administered orally once a day as one tablet.	Darunavir 800 mg PO QD + Ritonavir 100 mg PO QD + Emtricitabine 200 mg PO QD + Tenofovir disoproxil fumarate 300 mg PO QD + Placebo for Maraviroc PO QD Darunavir: Darunavir was administered orally once a day as two 400 mg tablets with food. When the 800 mg formulation tablet became available, it was substituted for the two 400 mg tablet. Ritonavir: Ritonavir was administered orally together with darunavir as one 100 mg tablet once daily with food. Tenofovir disoproxil fumarate: Tenofovir disoproxil fumarate was administered orally as one 300 mg tablet once a day. Emtricitabine: Emtricitabine was administered orally once a day as one 200 mg capsule. Placebo for Maraviroc: Placebo for maraviroc was administered orally once a day as one 150 mg tablet.
Measure Participants	117	111
Median (Inter-Quartile Range) [cells/mm^3]	234	188

5. Secondary Outcome

Title	CD8+ T-cell Change From Baseline to Week 48
Description	CD8+ T-cell change from baseline to week 48
Time Frame	At weeks 0 and 48

Outcome Measure Data

Analysis Population Description

As-treated analysis included only participants with available data at both baseline and week 48 who remained on their randomized MVC or TDF component by the time week 48 DEXA measurement was taken without an interruption of treatment for more than 10 weeks.

Arm/Group Title	MVC Arm (DRV/r + MVC + FTC + TDF Placebo)	TDF Arm (DRV/r + TDF + FTC + MVC Placebo)
Arm/Group Description	Darunavir 800 mg PO QD + Ritonavir 100 mg PO QD + Maraviroc 150 mg PO QD + Emtricitabine 200 mg PO QD + Placebo for Tenofovir disoproxil fumarate PO QD Darunavir: Darunavir was administered orally once a day as two 400 mg tablets with food. When the 800 mg formulation tablet became available, it was substituted for the two 400 mg tablet. Ritonavir: Ritonavir was administered orally together with darunavir as one 100 mg tablet once daily with food. Emtricitabine: Emtricitabine was administered orally once a day as one 200 mg capsule. Placebo for Tenofovir disoproxil fumarate: Placebo for tenofovir disoproxil fumarate was administered orally once a day as one tablet.	Darunavir 800 mg PO QD + Ritonavir 100 mg PO QD + Emtricitabine 200 mg PO QD + Tenofovir disoproxil fumarate 300 mg PO QD + Placebo for Maraviroc PO QD Darunavir: Darunavir was administered orally once a day as two 400 mg tablets with food. When the 800 mg formulation tablet became available, it was substituted for the two 400 mg tablet. Ritonavir: Ritonavir was administered orally together with darunavir as one 100 mg tablet once daily with food. Tenofovir disoproxil fumarate: Tenofovir disoproxil fumarate was administered orally as one 300 mg tablet once a day. Emtricitabine: Emtricitabine was administered orally once a day as one 200 mg capsule. Placebo for Maraviroc: Placebo for maraviroc was administered orally once a day as one 150 mg tablet.
Measure Participants	117	111
Median (Inter-Quartile Range) [cell/mm^3]	-6	-109

6. Secondary Outcome

Title	Percentage Change in Expression of CD38+/HLA-DR+ on CD4+ T Cells From Baseline to Week 48
Description	percentage change is define as [ (week 48 - week 0) / week 0 ] * 100%
Time Frame	At weeks 0 and 48

Outcome Measure Data

Analysis Population Description

As-treated analysis included only participants with available data at both baseline and week 48 who remained on their randomized MVC or TDF component by the time week 48 DEXA measurement was taken without an interruption of treatment for more than 10 weeks.

Arm/Group Title	MVC Arm (DRV/r + MVC + FTC + TDF Placebo)	TDF Arm (DRV/r + TDF + FTC + MVC Placebo)
Arm/Group Description	Darunavir 800 mg PO QD + Ritonavir 100 mg PO QD + Maraviroc 150 mg PO QD + Emtricitabine 200 mg PO QD + Placebo for Tenofovir disoproxil fumarate PO QD Darunavir: Darunavir was administered orally once a day as two 400 mg tablets with food. When the 800 mg formulation tablet became available, it was substituted for the two 400 mg tablet. Ritonavir: Ritonavir was administered orally together with darunavir as one 100 mg tablet once daily with food. Emtricitabine: Emtricitabine was administered orally once a day as one 200 mg capsule. Placebo for Tenofovir disoproxil fumarate: Placebo for tenofovir disoproxil fumarate was administered orally once a day as one tablet.	Darunavir 800 mg PO QD + Ritonavir 100 mg PO QD + Emtricitabine 200 mg PO QD + Tenofovir disoproxil fumarate 300 mg PO QD + Placebo for Maraviroc PO QD Darunavir: Darunavir was administered orally once a day as two 400 mg tablets with food. When the 800 mg formulation tablet became available, it was substituted for the two 400 mg tablet. Ritonavir: Ritonavir was administered orally together with darunavir as one 100 mg tablet once daily with food. Tenofovir disoproxil fumarate: Tenofovir disoproxil fumarate was administered orally as one 300 mg tablet once a day. Emtricitabine: Emtricitabine was administered orally once a day as one 200 mg capsule. Placebo for Maraviroc: Placebo for maraviroc was administered orally once a day as one 150 mg tablet.
Measure Participants	115	108
Median (Inter-Quartile Range) [percentage change]	-52.1	-48.6

7. Secondary Outcome

Title	Percentage Change in Expression of CD38+/HLA-DR+ on CD8+ T Cells From Baseline to Week 48
Description	percentage change is defined as [ (week 48 - week 0) / week 0 ] * 100%
Time Frame	At weeks 0 and 48

Outcome Measure Data

Analysis Population Description

As-treated analysis included only participants with available data at both baseline and week 48 who remained on their randomized MVC or TDF component by the time week 48 DEXA measurement was taken without an interruption of treatment for more than 10 weeks.

Arm/Group Title	MVC Arm: DRV/r + MVC + FTC + TDF Placebo	TDF Arm: DRV/r + TDF + FTC + MVC Placebo
Arm/Group Description	Darunavir 800 mg PO QD + Ritonavir 100 mg PO QD + Maraviroc 150 mg PO QD + Emtricitabine 200 mg PO QD + Placebo for Tenofovir disoproxil fumarate PO QD Darunavir: Darunavir was administered orally once a day as two 400 mg tablets with food. When the 800 mg formulation tablet became available, it was substituted for the two 400 mg tablet. Ritonavir: Ritonavir was administered orally together with darunavir as one 100 mg tablet once daily with food. Emtricitabine: Emtricitabine was administered orally once a day as one 200 mg capsule. Placebo for Tenofovir disoproxil fumarate: Placebo for tenofovir disoproxil fumarate was administered orally once a day as one tablet. Maraviroc: Maraviroc was administered orally once a day as one 150 mg tablet.	Darunavir 800 mg PO QD + Ritonavir 100 mg PO QD + Emtricitabine 200 mg PO QD + Tenofovir disoproxil fumarate 300 mg PO QD + Placebo for Maraviroc PO QD Darunavir: Darunavir was administered orally once a day as two 400 mg tablets with food. When the 800 mg formulation tablet became available, it was substituted for the two 400 mg tablet. Ritonavir: Ritonavir was administered orally together with darunavir as one 100 mg tablet once daily with food. Tenofovir disoproxil fumarate: Tenofovir disoproxil fumarate was administered orally as one 300 mg tablet once a day. Emtricitabine: Emtricitabine was administered orally once a day as one 200 mg capsule. Placebo for Maraviroc: Placebo for maraviroc was administered orally once a day as one tablet.
Measure Participants	115	108
Median (Inter-Quartile Range) [percentage change]	-59.5	-60.9

8. Secondary Outcome

Title	Percent Change in Expression of CD28+/CD57+ on CD8+ T Cells From Baseline to Week 48
Description	percentage change is define as [ (week 48 - week 0) / week 0 ] * 100%
Time Frame	At weeks 0 and 48

Outcome Measure Data

Analysis Population Description

As-treated analysis included only participants with available data at both baseline and week 48 who remained on their randomized MVC or TDF component by the time week 48 DEXA measurement was taken without an interruption of treatment for more than 10 weeks.

Arm/Group Title	MVC Arm (DRV/r + MVC + FTC + TDF Placebo)	TDF Arm (DRV/r + TDF + FTC + MVC Placebo)
Arm/Group Description	Darunavir 800 mg PO QD + Ritonavir 100 mg PO QD + Maraviroc 150 mg PO QD + Emtricitabine 200 mg PO QD + Placebo for Tenofovir disoproxil fumarate PO QD Darunavir: Darunavir was administered orally once a day as two 400 mg tablets with food. When the 800 mg formulation tablet became available, it was substituted for the two 400 mg tablet. Ritonavir: Ritonavir was administered orally together with darunavir as one 100 mg tablet once daily with food. Emtricitabine: Emtricitabine was administered orally once a day as one 200 mg capsule. Placebo for Tenofovir disoproxil fumarate: Placebo for tenofovir disoproxil fumarate was administered orally once a day as one tablet.	Darunavir 800 mg PO QD + Ritonavir 100 mg PO QD + Emtricitabine 200 mg PO QD + Tenofovir disoproxil fumarate 300 mg PO QD + Placebo for Maraviroc PO QD Darunavir: Darunavir was administered orally once a day as two 400 mg tablets with food. When the 800 mg formulation tablet became available, it was substituted for the two 400 mg tablet. Ritonavir: Ritonavir was administered orally together with darunavir as one 100 mg tablet once daily with food. Tenofovir disoproxil fumarate: Tenofovir disoproxil fumarate was administered orally as one 300 mg tablet once a day. Emtricitabine: Emtricitabine was administered orally once a day as one 200 mg capsule. Placebo for Maraviroc: Placebo for maraviroc was administered orally once a day as one 150 mg tablet.
Measure Participants	115	108
Median (Inter-Quartile Range) [percentage change]	-9.1	-11.2

9. Secondary Outcome

Title	Percent Change in Expression of CD57+ on CD8+ T Cells From Baseline to Week 48
Description	percentage change is define as [ (week 48 - week 0) / week 0 ] * 100%
Time Frame	At weeks 0 and 48

Outcome Measure Data

Analysis Population Description

As-treated analysis included only participants with available data at both baseline and week 48 who remained on their randomized MVC or TDF component by the time week 48 DEXA measurement was taken without an interruption of treatment for more than 10 weeks.

Arm/Group Title	MVC Arm (DRV/r + MVC + FTC + TDF Placebo)	TDF Arm (DRV/r + TDF + FTC + MVC Placebo)
Arm/Group Description	Darunavir 800 mg PO QD + Ritonavir 100 mg PO QD + Maraviroc 150 mg PO QD + Emtricitabine 200 mg PO QD + Placebo for Tenofovir disoproxil fumarate PO QD Darunavir: Darunavir was administered orally once a day as two 400 mg tablets with food. When the 800 mg formulation tablet became available, it was substituted for the two 400 mg tablet. Ritonavir: Ritonavir was administered orally together with darunavir as one 100 mg tablet once daily with food. Emtricitabine: Emtricitabine was administered orally once a day as one 200 mg capsule. Placebo for Tenofovir disoproxil fumarate: Placebo for tenofovir disoproxil fumarate was administered orally once a day as one tablet.	Darunavir 800 mg PO QD + Ritonavir 100 mg PO QD + Emtricitabine 200 mg PO QD + Tenofovir disoproxil fumarate 300 mg PO QD + Placebo for Maraviroc PO QD Darunavir: Darunavir was administered orally once a day as two 400 mg tablets with food. When the 800 mg formulation tablet became available, it was substituted for the two 400 mg tablet. Ritonavir: Ritonavir was administered orally together with darunavir as one 100 mg tablet once daily with food. Tenofovir disoproxil fumarate: Tenofovir disoproxil fumarate was administered orally as one 300 mg tablet once a day. Emtricitabine: Emtricitabine was administered orally once a day as one 200 mg capsule. Placebo for Maraviroc: Placebo for maraviroc was administered orally once a day as one 150 mg tablet.
Measure Participants	115	108
Median (Inter-Quartile Range) [percentage change]	-3.5	-4.6

10. Secondary Outcome

Title	Percent Change in Expression of CD28+ on CD8+ T Cells From Baseline to Week 48
Description	percentage change is define as [ (week 48 - week 0) / week 0 ] * 100%
Time Frame	At weeks 0 and 48

Outcome Measure Data

Analysis Population Description

As-treated analysis included only participants with available data at both baseline and week 48 who remained on their randomized MVC or TDF component by the time week 48 DEXA measurement was taken without an interruption of treatment for more than 10 weeks.

Arm/Group Title	MVC Arm (DRV/r + MVC + FTC + TDF Placebo)	TDF Arm (DRV/r + TDF + FTC + MVC Placebo)
Arm/Group Description	Darunavir 800 mg PO QD + Ritonavir 100 mg PO QD + Maraviroc 150 mg PO QD + Emtricitabine 200 mg PO QD + Placebo for Tenofovir disoproxil fumarate PO QD Darunavir: Darunavir was administered orally once a day as two 400 mg tablets with food. When the 800 mg formulation tablet became available, it was substituted for the two 400 mg tablet. Ritonavir: Ritonavir was administered orally together with darunavir as one 100 mg tablet once daily with food. Emtricitabine: Emtricitabine was administered orally once a day as one 200 mg capsule. Placebo for Tenofovir disoproxil fumarate: Placebo for tenofovir disoproxil fumarate was administered orally once a day as one tablet.	Darunavir 800 mg PO QD + Ritonavir 100 mg PO QD + Emtricitabine 200 mg PO QD + Tenofovir disoproxil fumarate 300 mg PO QD + Placebo for Maraviroc PO QD Darunavir: Darunavir was administered orally once a day as two 400 mg tablets with food. When the 800 mg formulation tablet became available, it was substituted for the two 400 mg tablet. Ritonavir: Ritonavir was administered orally together with darunavir as one 100 mg tablet once daily with food. Tenofovir disoproxil fumarate: Tenofovir disoproxil fumarate was administered orally as one 300 mg tablet once a day. Emtricitabine: Emtricitabine was administered orally once a day as one 200 mg capsule. Placebo for Maraviroc: Placebo for maraviroc was administered orally once a day as one 150 mg tablet.
Measure Participants	115	108
Median (Inter-Quartile Range) [percentage change]	11.9	14.0

11. Secondary Outcome

Title	Percent Change in Expression of RANKL+ on CD8+ T Cells From Baseline to Week 48
Description	percentage change is defined as [ (week 48 - week 0) / week 0 ] * 100%
Time Frame	At weeks 0 and 48

Outcome Measure Data

Analysis Population Description

As-treated analysis included only participants with available data at both baseline and week 48 who remained on their randomized MVC or TDF component by the time week 48 DEXA measurement was taken without an interruption of treatment for more than 10 weeks.

Arm/Group Title	MVC Arm (DRV/r + MVC + FTC + TDF Placebo)	TDF Arm (DRV/r + TDF + FTC + MVC Placebo)
Arm/Group Description	Darunavir 800 mg PO QD + Ritonavir 100 mg PO QD + Maraviroc 150 mg PO QD + Emtricitabine 200 mg PO QD + Placebo for Tenofovir disoproxil fumarate PO QD Darunavir: Darunavir was administered orally once a day as two 400 mg tablets with food. When the 800 mg formulation tablet became available, it was substituted for the two 400 mg tablet. Ritonavir: Ritonavir was administered orally together with darunavir as one 100 mg tablet once daily with food. Emtricitabine: Emtricitabine was administered orally once a day as one 200 mg capsule. Placebo for Tenofovir disoproxil fumarate: Placebo for tenofovir disoproxil fumarate was administered orally once a day as one tablet.	Darunavir 800 mg PO QD + Ritonavir 100 mg PO QD + Emtricitabine 200 mg PO QD + Tenofovir disoproxil fumarate 300 mg PO QD + Placebo for Maraviroc PO QD Darunavir: Darunavir was administered orally once a day as two 400 mg tablets with food. When the 800 mg formulation tablet became available, it was substituted for the two 400 mg tablet. Ritonavir: Ritonavir was administered orally together with darunavir as one 100 mg tablet once daily with food. Tenofovir disoproxil fumarate: Tenofovir disoproxil fumarate was administered orally as one 300 mg tablet once a day. Emtricitabine: Emtricitabine was administered orally once a day as one 200 mg capsule. Placebo for Maraviroc: Placebo for maraviroc was administered orally once a day as one 150 mg tablet.
Measure Participants	115	108
Median (Inter-Quartile Range) [percentage change]	-20.7	-17.0

12. Secondary Outcome

Title	Change in Levels of IL-6 From Baseline to Week 48
Description	Change in levels of Interleukin 6 (IL-6) from baseline to week 48
Time Frame	At weeks 0 and 48

Outcome Measure Data

Analysis Population Description

As-treated analysis included only participants with available data at both baseline and week 48 who remained on their randomized MVC or TDF component by the time week 48 DEXA measurement was taken without an interruption of treatment for more than 10 weeks.

Arm/Group Title	MVC Arm (DRV/r + MVC + FTC + TDF Placebo)	TDF Arm (DRV/r + TDF + FTC + MVC Placebo)
Arm/Group Description	Darunavir 800 mg PO QD + Ritonavir 100 mg PO QD + Maraviroc 150 mg PO QD + Emtricitabine 200 mg PO QD + Placebo for Tenofovir disoproxil fumarate PO QD Darunavir: Darunavir was administered orally once a day as two 400 mg tablets with food. When the 800 mg formulation tablet became available, it was substituted for the two 400 mg tablet. Ritonavir: Ritonavir was administered orally together with darunavir as one 100 mg tablet once daily with food. Emtricitabine: Emtricitabine was administered orally once a day as one 200 mg capsule. Placebo for Tenofovir disoproxil fumarate: Placebo for tenofovir disoproxil fumarate was administered orally once a day as one tablet.	Darunavir 800 mg PO QD + Ritonavir 100 mg PO QD + Emtricitabine 200 mg PO QD + Tenofovir disoproxil fumarate 300 mg PO QD + Placebo for Maraviroc PO QD Darunavir: Darunavir was administered orally once a day as two 400 mg tablets with food. When the 800 mg formulation tablet became available, it was substituted for the two 400 mg tablet. Ritonavir: Ritonavir was administered orally together with darunavir as one 100 mg tablet once daily with food. Tenofovir disoproxil fumarate: Tenofovir disoproxil fumarate was administered orally as one 300 mg tablet once a day. Emtricitabine: Emtricitabine was administered orally once a day as one 200 mg capsule. Placebo for Maraviroc: Placebo for maraviroc was administered orally once a day as one 150 mg tablet.
Measure Participants	116	107
Median (Inter-Quartile Range) [pg/ml]	-0.21	-0.12

13. Secondary Outcome

Title	Change in Level of IP-10 From Baseline to Week 48
Description	Change in level of Interferon gamma-induced protein 10 (IP-10) from baseline to week 48
Time Frame	At weeks 0 and 48

Outcome Measure Data

Analysis Population Description

As-treated analysis included only participants with available data at both baseline and week 48 who remained on their randomized MVC or TDF component by the time week 48 DEXA measurement was taken without an interruption of treatment for more than 10 weeks.

Arm/Group Title	MVC Arm (DRV/r + MVC + FTC + TDF Placebo)	TDF Arm (DRV/r + TDF + FTC + MVC Placebo)
Arm/Group Description	Darunavir 800 mg PO QD + Ritonavir 100 mg PO QD + Maraviroc 150 mg PO QD + Emtricitabine 200 mg PO QD + Placebo for Tenofovir disoproxil fumarate PO QD Darunavir: Darunavir was administered orally once a day as two 400 mg tablets with food. When the 800 mg formulation tablet became available, it was substituted for the two 400 mg tablet. Ritonavir: Ritonavir was administered orally together with darunavir as one 100 mg tablet once daily with food. Emtricitabine: Emtricitabine was administered orally once a day as one 200 mg capsule. Placebo for Tenofovir disoproxil fumarate: Placebo for tenofovir disoproxil fumarate was administered orally once a day as one tablet.	Darunavir 800 mg PO QD + Ritonavir 100 mg PO QD + Emtricitabine 200 mg PO QD + Tenofovir disoproxil fumarate 300 mg PO QD + Placebo for Maraviroc PO QD Darunavir: Darunavir was administered orally once a day as two 400 mg tablets with food. When the 800 mg formulation tablet became available, it was substituted for the two 400 mg tablet. Ritonavir: Ritonavir was administered orally together with darunavir as one 100 mg tablet once daily with food. Tenofovir disoproxil fumarate: Tenofovir disoproxil fumarate was administered orally as one 300 mg tablet once a day. Emtricitabine: Emtricitabine was administered orally once a day as one 200 mg capsule. Placebo for Maraviroc: Placebo for maraviroc was administered orally once a day as one 150 mg tablet.
Measure Participants	116	107
Median (Inter-Quartile Range) [pg/ml]	-198	-170

14. Secondary Outcome

Title	Change in Levels of sCD163 From Baseline to Week 48
Description	Change in levels of soluble CD163 from baseline to week 48
Time Frame	At weeks 0 and 48

Outcome Measure Data

Analysis Population Description

As-treated analysis included only participants with available data at both baseline and week 48 who remained on their randomized MVC or TDF component by the time week 48 DEXA measurement was taken without an interruption of treatment for more than 10 weeks.

Arm/Group Title	MVC Arm (DRV/r + MVC + FTC + TDF Placebo)	TDF Arm (DRV/r + TDF + FTC + MVC Placebo)
Arm/Group Description	Darunavir 800 mg PO QD + Ritonavir 100 mg PO QD + Maraviroc 150 mg PO QD + Emtricitabine 200 mg PO QD + Placebo for Tenofovir disoproxil fumarate PO QD Darunavir: Darunavir was administered orally once a day as two 400 mg tablets with food. When the 800 mg formulation tablet became available, it was substituted for the two 400 mg tablet. Ritonavir: Ritonavir was administered orally together with darunavir as one 100 mg tablet once daily with food. Emtricitabine: Emtricitabine was administered orally once a day as one 200 mg capsule. Placebo for Tenofovir disoproxil fumarate: Placebo for tenofovir disoproxil fumarate was administered orally once a day as one tablet.	Darunavir 800 mg PO QD + Ritonavir 100 mg PO QD + Emtricitabine 200 mg PO QD + Tenofovir disoproxil fumarate 300 mg PO QD + Placebo for Maraviroc PO QD Darunavir: Darunavir was administered orally once a day as two 400 mg tablets with food. When the 800 mg formulation tablet became available, it was substituted for the two 400 mg tablet. Ritonavir: Ritonavir was administered orally together with darunavir as one 100 mg tablet once daily with food. Tenofovir disoproxil fumarate: Tenofovir disoproxil fumarate was administered orally as one 300 mg tablet once a day. Emtricitabine: Emtricitabine was administered orally once a day as one 200 mg capsule. Placebo for Maraviroc: Placebo for maraviroc was administered orally once a day as one 150 mg tablet.
Measure Participants	116	107
Median (Inter-Quartile Range) [ng/ml]	-250	-258

15. Secondary Outcome

Title	Change in Levels of sCD14 From Baseline
Description	Change in levels of soluble CD14 from baseline
Time Frame	At weeks 0 and 48

Outcome Measure Data

Analysis Population Description

As-treated analysis included only participants with available data at both baseline and week 48 who remained on their randomized MVC or TDF component by the time week 48 DEXA measurement was taken without an interruption of treatment for more than 10 weeks.

Arm/Group Title	MVC Arm (DRV/r + MVC + FTC + TDF Placebo)	TDF Arm (DRV/r + TDF + FTC + MVC Placebo)
Arm/Group Description	Darunavir 800 mg PO QD + Ritonavir 100 mg PO QD + Maraviroc 150 mg PO QD + Emtricitabine 200 mg PO QD + Placebo for Tenofovir disoproxil fumarate PO QD Darunavir: Darunavir was administered orally once a day as two 400 mg tablets with food. When the 800 mg formulation tablet became available, it was substituted for the two 400 mg tablet. Ritonavir: Ritonavir was administered orally together with darunavir as one 100 mg tablet once daily with food. Emtricitabine: Emtricitabine was administered orally once a day as one 200 mg capsule. Placebo for Tenofovir disoproxil fumarate: Placebo for tenofovir disoproxil fumarate was administered orally once a day as one tablet.	Darunavir 800 mg PO QD + Ritonavir 100 mg PO QD + Emtricitabine 200 mg PO QD + Tenofovir disoproxil fumarate 300 mg PO QD + Placebo for Maraviroc PO QD Darunavir: Darunavir was administered orally once a day as two 400 mg tablets with food. When the 800 mg formulation tablet became available, it was substituted for the two 400 mg tablet. Ritonavir: Ritonavir was administered orally together with darunavir as one 100 mg tablet once daily with food. Tenofovir disoproxil fumarate: Tenofovir disoproxil fumarate was administered orally as one 300 mg tablet once a day. Emtricitabine: Emtricitabine was administered orally once a day as one 200 mg capsule. Placebo for Maraviroc: Placebo for maraviroc was administered orally once a day as one 150 mg tablet.
Measure Participants	116	107
Median (Inter-Quartile Range) [ng/ml]	-103	-10

16. Secondary Outcome

Title	Change in Levels of D-dimer From Baseline
Description	Change in levels of D-dimer from baseline
Time Frame	At weeks 0 and 48

Outcome Measure Data

Analysis Population Description

As-treated analysis included only participants with available data at both baseline and week 48 who remained on their randomized MVC or TDF component by the time week 48 DEXA measurement was taken without an interruption of treatment for more than 10 weeks.

Arm/Group Title	MVC Arm (DRV/r + MVC + FTC + TDF Placebo)	TDF Arm (DRV/r + TDF + FTC + MVC Placebo)
Arm/Group Description	Darunavir 800 mg PO QD + Ritonavir 100 mg PO QD + Maraviroc 150 mg PO QD + Emtricitabine 200 mg PO QD + Placebo for Tenofovir disoproxil fumarate PO QD Darunavir: Darunavir was administered orally once a day as two 400 mg tablets with food. When the 800 mg formulation tablet became available, it was substituted for the two 400 mg tablet. Ritonavir: Ritonavir was administered orally together with darunavir as one 100 mg tablet once daily with food. Emtricitabine: Emtricitabine was administered orally once a day as one 200 mg capsule. Placebo for Tenofovir disoproxil fumarate: Placebo for tenofovir disoproxil fumarate was administered orally once a day as one tablet.	Darunavir 800 mg PO QD + Ritonavir 100 mg PO QD + Emtricitabine 200 mg PO QD + Tenofovir disoproxil fumarate 300 mg PO QD + Placebo for Maraviroc PO QD Darunavir: Darunavir was administered orally once a day as two 400 mg tablets with food. When the 800 mg formulation tablet became available, it was substituted for the two 400 mg tablet. Ritonavir: Ritonavir was administered orally together with darunavir as one 100 mg tablet once daily with food. Tenofovir disoproxil fumarate: Tenofovir disoproxil fumarate was administered orally as one 300 mg tablet once a day. Emtricitabine: Emtricitabine was administered orally once a day as one 200 mg capsule. Placebo for Maraviroc: Placebo for maraviroc was administered orally once a day as one 150 mg tablet.
Measure Participants	115	106
Median (Inter-Quartile Range) [ng/ml]	-82	-61

17. Secondary Outcome

Title	Cumulative Probability of Virologic Failure by Week 48
Description	Confirmed virologic failure is defined as confirmed plasma HIV-1 RNA levels > 1000 copies/mL at or after week 16 and before week 24, or confirmed HIV-1 RNA levels> 200 copies/mL at or after week 24. Participants who discontinued the study with an unconfirmed virologic failure (HIV-1 RNA > 1000 copies at 16 weeks or HIV-1 RNA level > 200 copies/mL at or after week 24) are considered as virologic failures at the study visit week of the unconfirmed value. Time to virologic failure is defined as the time from study entry to the planned visit week of the initial failure. Product-limit estimates for the survival function were used to estimate the cumulative probability of virologic failure over time and its corresponding 95% confidence interval for each treatment group.
Time Frame	From study treatment initiation to week 48

Outcome Measure Data

Analysis Population Description

All participants who started study treatment

Arm/Group Title	MVC Arm (DRV/r + MVC + FTC + TDF Placebo)	TDF Arm (DRV/r + TDF + FTC + MVC Placebo)
Arm/Group Description	Darunavir 800 mg PO QD + Ritonavir 100 mg PO QD + Maraviroc 150 mg PO QD + Emtricitabine 200 mg PO QD + Placebo for Tenofovir disoproxil fumarate PO QD Darunavir: Darunavir was administered orally once a day as two 400 mg tablets with food. When the 800 mg formulation tablet became available, it was substituted for the two 400 mg tablet. Ritonavir: Ritonavir was administered orally together with darunavir as one 100 mg tablet once daily with food. Emtricitabine: Emtricitabine was administered orally once a day as one 200 mg capsule. Placebo for Tenofovir disoproxil fumarate: Placebo for tenofovir disoproxil fumarate was administered orally once a day as one tablet.	Darunavir 800 mg PO QD + Ritonavir 100 mg PO QD + Emtricitabine 200 mg PO QD + Tenofovir disoproxil fumarate 300 mg PO QD + Placebo for Maraviroc PO QD Darunavir: Darunavir was administered orally once a day as two 400 mg tablets with food. When the 800 mg formulation tablet became available, it was substituted for the two 400 mg tablet. Ritonavir: Ritonavir was administered orally together with darunavir as one 100 mg tablet once daily with food. Tenofovir disoproxil fumarate: Tenofovir disoproxil fumarate was administered orally as one 300 mg tablet once a day. Emtricitabine: Emtricitabine was administered orally once a day as one 200 mg capsule. Placebo for Maraviroc: Placebo for maraviroc was administered orally once a day as one 150 mg tablet.
Measure Participants	130	129
Number (95% Confidence Interval) [cumulative probability per 100 persons]	6	5

18. Secondary Outcome

Title	Number of Participants Who Experienced Bone Fractures
Description	Number of participants who experienced bone fractures during the study
Time Frame	From study treatment initiation to week 48

Outcome Measure Data

Analysis Population Description

All participants who started study treatment

Arm/Group Title	MVC Arm (DRV/r + MVC + FTC + TDF Placebo)	TDF Arm (DRV/r + TDF + FTC + MVC Placebo)
Arm/Group Description	Darunavir 800 mg PO QD + Ritonavir 100 mg PO QD + Maraviroc 150 mg PO QD + Emtricitabine 200 mg PO QD + Placebo for Tenofovir disoproxil fumarate PO QD Darunavir: Darunavir was administered orally once a day as two 400 mg tablets with food. When the 800 mg formulation tablet became available, it was substituted for the two 400 mg tablet. Ritonavir: Ritonavir was administered orally together with darunavir as one 100 mg tablet once daily with food. Emtricitabine: Emtricitabine was administered orally once a day as one 200 mg capsule. Placebo for Tenofovir disoproxil fumarate: Placebo for tenofovir disoproxil fumarate was administered orally once a day as one tablet.	Darunavir 800 mg PO QD + Ritonavir 100 mg PO QD + Emtricitabine 200 mg PO QD + Tenofovir disoproxil fumarate 300 mg PO QD + Placebo for Maraviroc PO QD Darunavir: Darunavir was administered orally once a day as two 400 mg tablets with food. When the 800 mg formulation tablet became available, it was substituted for the two 400 mg tablet. Ritonavir: Ritonavir was administered orally together with darunavir as one 100 mg tablet once daily with food. Tenofovir disoproxil fumarate: Tenofovir disoproxil fumarate was administered orally as one 300 mg tablet once a day. Emtricitabine: Emtricitabine was administered orally once a day as one 200 mg capsule. Placebo for Maraviroc: Placebo for maraviroc was administered orally once a day as one 150 mg tablet.
Measure Participants	130	129
Number [participants]	2 1.5%	2 1.6%

19. Secondary Outcome

Title	Number of Participants Who Died During the Study
Description	Number of participants who died during the study
Time Frame	From study treatment initiation to week 48

Outcome Measure Data

Analysis Population Description

All participants who started study treatment

Arm/Group Title	MVC Arm (DRV/r + MVC + FTC + TDF Placebo)	TDF Arm (DRV/r + TDF + FTC + MVC Placebo)
Arm/Group Description	Darunavir 800 mg PO QD + Ritonavir 100 mg PO QD + Maraviroc 150 mg PO QD + Emtricitabine 200 mg PO QD + Placebo for Tenofovir disoproxil fumarate PO QD Darunavir: Darunavir was administered orally once a day as two 400 mg tablets with food. When the 800 mg formulation tablet became available, it was substituted for the two 400 mg tablet. Ritonavir: Ritonavir was administered orally together with darunavir as one 100 mg tablet once daily with food. Emtricitabine: Emtricitabine was administered orally once a day as one 200 mg capsule. Placebo for Tenofovir disoproxil fumarate: Placebo for tenofovir disoproxil fumarate was administered orally once a day as one tablet.	Darunavir 800 mg PO QD + Ritonavir 100 mg PO QD + Emtricitabine 200 mg PO QD + Tenofovir disoproxil fumarate 300 mg PO QD + Placebo for Maraviroc PO QD Darunavir: Darunavir was administered orally once a day as two 400 mg tablets with food. When the 800 mg formulation tablet became available, it was substituted for the two 400 mg tablet. Ritonavir: Ritonavir was administered orally together with darunavir as one 100 mg tablet once daily with food. Tenofovir disoproxil fumarate: Tenofovir disoproxil fumarate was administered orally as one 300 mg tablet once a day. Emtricitabine: Emtricitabine was administered orally once a day as one 200 mg capsule. Placebo for Maraviroc: Placebo for maraviroc was administered orally once a day as one 150 mg tablet.
Measure Participants	130	129
Number [participants]	0 0%	0 0%

20. Secondary Outcome

Title	Number of Participants Who Developed Grade 3 or 4 Primary Adverse Events
Description	Grade 3 or 4 primary adverse events includes primary signs/symptoms, primary laboratory abnormalities, or primary diagnoses. See DAIDS AE Grading Table Version 1.0, Dec 2004 (Clarification, Aug 2009)
Time Frame	From study treatment initiation to week 48

Outcome Measure Data

Analysis Population Description

All participants who initiated study treatment

Arm/Group Title	MVC Arm (DRV/r + MVC + FTC + TDF Placebo)	TDF Arm (DRV/r + TDF + FTC + MVC Placebo)
Arm/Group Description	Darunavir 800 mg PO QD + Ritonavir 100 mg PO QD + Maraviroc 150 mg PO QD + Emtricitabine 200 mg PO QD + Placebo for Tenofovir disoproxil fumarate PO QD Darunavir: Darunavir was administered orally once a day as two 400 mg tablets with food. When the 800 mg formulation tablet became available, it was substituted for the two 400 mg tablet. Ritonavir: Ritonavir was administered orally together with darunavir as one 100 mg tablet once daily with food. Emtricitabine: Emtricitabine was administered orally once a day as one 200 mg capsule. Placebo for Tenofovir disoproxil fumarate: Placebo for tenofovir disoproxil fumarate was administered orally once a day as one tablet.	Darunavir 800 mg PO QD + Ritonavir 100 mg PO QD + Emtricitabine 200 mg PO QD + Tenofovir disoproxil fumarate 300 mg PO QD + Placebo for Maraviroc PO QD Darunavir: Darunavir was administered orally once a day as two 400 mg tablets with food. When the 800 mg formulation tablet became available, it was substituted for the two 400 mg tablet. Ritonavir: Ritonavir was administered orally together with darunavir as one 100 mg tablet once daily with food. Tenofovir disoproxil fumarate: Tenofovir disoproxil fumarate was administered orally as one 300 mg tablet once a day. Emtricitabine: Emtricitabine was administered orally once a day as one 200 mg capsule. Placebo for Maraviroc: Placebo for maraviroc was administered orally once a day as one 150 mg tablet.
Measure Participants	130	129
Number [participants]	16 12.3%	22 17.1%

Adverse Events

Time Frame	week 0 to week 48
Adverse Event Reporting Description	Adverse events from participants' first study treatment date to off study date. See DAIDS AE Grading Table Version 1.0, Dec 2004 (Clarification, Aug 2009). All targeted events (see protocol 6.3.4), grade >=3 signs/symptoms or laboratory toxicities, or any adverse events that led to a change in study treatment were required to be recorded.
Arm/Group Title	MVC Arm (DRV/r + MVC + FTC + TDF Placebo)		TDF Arm (DRV/r + TDF + FTC + MVC Placebo)
Arm/Group Description	Darunavir 800 mg PO QD + Ritonavir 100 mg PO QD + Maraviroc 150 mg PO QD + Emtricitabine 200 mg PO QD + Placebo for Tenofovir disoproxil fumarate PO QD Darunavir: Darunavir was administered orally once a day as two 400 mg tablets with food. When the 800 mg formulation tablet became available, it was substituted for the two 400 mg tablet. Ritonavir: Ritonavir was administered orally together with darunavir as one 100 mg tablet once daily with food. Emtricitabine: Emtricitabine was administered orally once a day as one 200 mg capsule. Placebo for Tenofovir disoproxil fumarate: Placebo for tenofovir disoproxil fumarate was administered orally once a day as one tablet.		Darunavir 800 mg PO QD + Ritonavir 100 mg PO QD + Emtricitabine 200 mg PO QD + Tenofovir disoproxil fumarate 300 mg PO QD + Placebo for Maraviroc PO QD Darunavir: Darunavir was administered orally once a day as two 400 mg tablets with food. When the 800 mg formulation tablet became available, it was substituted for the two 400 mg tablet. Ritonavir: Ritonavir was administered orally together with darunavir as one 100 mg tablet once daily with food. Tenofovir disoproxil fumarate: Tenofovir disoproxil fumarate was administered orally as one 300 mg tablet once a day. Emtricitabine: Emtricitabine was administered orally once a day as one 200 mg capsule. Placebo for Maraviroc: Placebo for maraviroc was administered orally once a day as one 150 mg tablet.
All Cause Mortality
	MVC Arm (DRV/r + MVC + FTC + TDF Placebo)		TDF Arm (DRV/r + TDF + FTC + MVC Placebo)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	MVC Arm (DRV/r + MVC + FTC + TDF Placebo)		TDF Arm (DRV/r + TDF + FTC + MVC Placebo)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	10/130 (7.7%)		4/129 (3.1%)
Gastrointestinal disorders
Intestinal ischaemia	1/130 (0.8%)		0/129 (0%)
Infections and infestations
Abscess limb	0/130 (0%)		1/129 (0.8%)
Perineal abscess	1/130 (0.8%)		0/129 (0%)
Pneumonia	2/130 (1.5%)		0/129 (0%)
Injury, poisoning and procedural complications
Road traffic accident	1/130 (0.8%)		0/129 (0%)
Investigations
Weight decreased	1/130 (0.8%)		0/129 (0%)
Metabolism and nutrition disorders
Abnormal loss of weight	0/130 (0%)		1/129 (0.8%)
Nervous system disorders
Headache	0/130 (0%)		1/129 (0.8%)
Pregnancy, puerperium and perinatal conditions
Abortion spontaneous	1/130 (0.8%)		0/129 (0%)
Psychiatric disorders
Major depression	1/130 (0.8%)		0/129 (0%)
Suicide attempt	0/130 (0%)		1/129 (0.8%)
Respiratory, thoracic and mediastinal disorders
Epistaxis	1/130 (0.8%)		0/129 (0%)
Skin and subcutaneous tissue disorders
Rash	1/130 (0.8%)		0/129 (0%)
Other (Not Including Serious) Adverse Events
	MVC Arm (DRV/r + MVC + FTC + TDF Placebo)		TDF Arm (DRV/r + TDF + FTC + MVC Placebo)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	101/130 (77.7%)		78/129 (60.5%)
Investigations
Alanine aminotransferase increased	12/130 (9.2%)		15/129 (11.6%)
Aspartate aminotransferase increased	12/130 (9.2%)		10/129 (7.8%)
Blood cholesterol increased	60/130 (46.2%)		39/129 (30.2%)
Blood creatinine increased	3/130 (2.3%)		8/129 (6.2%)
Blood glucose decreased	7/130 (5.4%)		5/129 (3.9%)
Blood glucose increased	12/130 (9.2%)		9/129 (7%)
Blood phosphorus decreased	27/130 (20.8%)		24/129 (18.6%)
Blood sodium decreased	10/130 (7.7%)		11/129 (8.5%)
Low density lipoprotein increased	46/130 (35.4%)		26/129 (20.2%)
Neutrophil count decreased	13/130 (10%)		10/129 (7.8%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.