High Dose Vitamin D and Calcium for Bone Health in Individuals Initiating HAART

• ClinicalTrials.gov Identifier: NCT01403051
• Recruitment Status: Completed
• First Posted: July 27, 2011
• Results First Posted: March 19, 2014
• Last Update Posted: October 12, 2018
• Sponsor: AIDS Clinical Trials Group
• Collaborator: National Institute of Allergy and Infectious Diseases (NIAID)
• Information provided by (Responsible Party): AIDS Clinical Trials Group

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: HIV-1 Infection
• Interventions: Drug: EFV/FTC/TDF; Drug: Calcium Carbonate; Drug: Vitamin D3; Drug: Placebo for calcium carbonate; Drug: Placebo for vitamin D3
• Enrollment: 167

Participant Flow

Recruitment Details	A5280 opened under version 1.0 on September 15, 2011, and the first subject was randomized on September 26, 2011. Accrual to the study closed on March 2, 2012, with a total of 167 subjects enrolled from 39 sites within the US.
Pre-assignment Details	Subjects were randomized with a 1:1 ratio at enrollment.

Arm/Group Title	Arm A: Vitamin D3 and Calcium Carbonate Plus EFV/FTC/TDF	Arm B: Vitamin D3 Placebo and Calcium Placebo Plus EFV/FTC/TDF
Arm/Group Description	The participants were administered vitamin D3, calcium carbonate and FDC efavirenz/emtricitabine/tenofovir disoproxil fumarate (Atripla). Vitamin D3: One Vitamin D3 4000 IU capsule taken orally once daily with food for 48 weeks. Calcium Carbonate: Calcium carbonate 500 mg tablet taken orally twice daily with food for 48 weeks. Atripla: FDC efavirenz/emtricitabine/tenofovir disoproxil fumarate (EFV/FTC/TDF) 600 mg/200 mg/ 300 mg tablet taken orally once daily at bedtime on an empty stomach.	The participants were administered a placebo for vitamin D3, a placebo for calcium carbonate, and FDC efavirenz/emtricitabine/tenofovir disoproxil fumarate (Atripla) Placebo for vitamin D3: A placebo for vitamin D3 once daily taken orally as one capsule with food for 48 weeks. Placebo for calcium carbonate: A placebo for calcium carbonate twice daily taken orally as one x 0 mg tablets with food for 48 weeks Atripla: FDC efavirenz/emtricitabine/tenofovir disoproxil fumarate (EFV/FTC/TDF) 600 mg/200 mg/ 300 mg tablet taken orally once daily at bedtime on an empty stomach.
Period Title: Overall Study
Started	81	86
Initiated Study Treatment	81	86
Completed	71	80
Not Completed	10	6
Reason Not Completed
Protocol Violation	2	0
Death	1	0
Withdrawal by Subject	2	1
Lost to Follow-up	5	5

Baseline Characteristics

Arm/Group Title		Arm A: Vitamin D3 and Calcium Carbonate Plus EFV/FTC/TDF	Arm B: Vitamin D3 Placebo and Calcium Placebo Plus EFV/FTC/TDF	Total
Arm/Group Description		The participants were administered vitamin D3, calcium carbonate and FDC efavirenz/emtricitabine/tenofovir disoproxil fumarate (Atripla). Vitamin D3: One Vitamin D3 4000 IU capsule taken orally once daily with food for 48 weeks. Calcium Carbonate: Calcium carbonate 500 mg tablet taken orally twice daily with food for 48 weeks. Atripla: FDC efavirenz/emtricitabine/tenofovir disoproxil fumarate (EFV/FTC/TDF) 600 mg/200 mg/ 300 mg tablet taken orally once daily at bedtime on an empty stomach.	The participants were administered a placebo for vitamin D3, a placebo for calcium carbonate, and FDC efavirenz/emtricitabine/tenofovir disoproxil fumarate (Atripla). Placebo for vitamin D3: A placebo for vitamin D3 once daily taken orally as one capsule with food for 48 weeks. Placebo for calcium carbonate: A placebo for calcium carbonate twice daily taken orally as one x 0 mg tablets with food for 48 weeks Atripla: FDC efavirenz/emtricitabine/tenofovir disoproxil fumarate (EFV/FTC/TDF) 600 mg/200 mg/ 300 mg tablet taken orally once daily at bedtime on an empty stomach.	Total of all reporting groups
Overall Number of Baseline Participants		79	86	165
Baseline Analysis Population Description		Includes only subjects who did not have eligibility violations
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	79 participants	86 participants	165 participants
	<=18 years	0 0.0%	0 0.0%	0 0.0%
	Between 18 and 65 years	76 96.2%	85 98.8%	161 97.6%
	>=65 years	3 3.8%	1 1.2%	4 2.4%
Age, Continuous; Median (Inter-Quartile Range); Unit of measure: Years
	Number Analyzed	79 participants	86 participants	165 participants
		36; (28 to 47)	31; (25 to 44)	33; (26 to 46)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	79 participants	86 participants	165 participants
	Female	7 8.9%	9 10.5%	16 9.7%
	Male	72 91.1%	77 89.5%	149 90.3%
Race/Ethnicity, Customized; Measure Type: Number; Unit of measure: Participants	Number Analyzed	79 participants	86 participants	165 participants
White Non-Hispanic		28	33	61
Black Non-Hispanic		24	30	54
Hispanic (Regardless of Race)		23	18	41
Asian, Pacific Islander		2	5	7
American Indian, Alaskan Native		2	0	2
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
United States	Number Analyzed	79 participants	86 participants	165 participants
		79	86	165
HIV-1 RNA level [1]; Median (Inter-Quartile Range); Unit of measure: Log10 copies/mL
	Number Analyzed	79 participants	86 participants	165 participants
		4.5; (4.1 to 5.1)	4.5; (4.0 to 5.1)	4.5; (4.1 to 5.1)
		[1] Measure Description: Entry HIV-RNA level (log10 copies/mL)
CD4 count [1]; Median (Inter-Quartile Range); Unit of measure: Cells/mm3
	Number Analyzed	79 participants	86 participants	165 participants
		339; (230 to 500)	342; (232 to 454)	341; (230 to 490)
		[1] Measure Description: Entry total CD4 count (cells/mm3)

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

The primary analysis is intent-to-treat (ITT) which is limited to eligible subjects who have baseline and week 48 follow-up regardless of treatment change or discontinuation.

Arm/Group Title	Arm A: Vitamin D3 and Calcium Carbonate Plus EFV/FTC/TDF	Arm B: Vitamin D3 Placebo and Calcium Placebo Plus EFV/FTC/TDF
Arm/Group Description:	The participants were administered vitamin D3, calcium carbonate and FDC efavirenz/emtricitabine/tenofovir disoproxil fumarate (Atripla). Vitamin D3: One Vitamin D3 4000 IU capsule taken orally once daily with food for 48 weeks. Calcium Carbonate: Calcium carbonate 500 mg tablet taken orally twice daily with food for 48 weeks. Atripla: FDC efavirenz/emtricitabine/tenofovir disoproxil fumarate (EFV/FTC/TDF) 600 mg/200 mg/ 300 mg tablet taken orally once daily at bedtime on an empty stomach.	The participants were administered a placebo for vitamin D3, a placebo for calcium carbonate, and FDC efavirenz/emtricitabine/tenofovir disoproxil fumarate (Atripla). Placebo for vitamin D3: A placebo for vitamin D3 once daily taken orally as one capsule with food for 48 weeks. Placebo for calcium carbonate: A placebo for calcium carbonate twice daily taken orally as one x 0 mg tablets with food for 48 weeks Atripla: FDC efavirenz/emtricitabine/tenofovir disoproxil fumarate (EFV/FTC/TDF) 600 mg/200 mg/ 300 mg tablet taken orally once daily at bedtime on an empty stomach.
Overall Number of Participants Analyzed	65	77
Median (Inter-Quartile Range); Unit of Measure: percentage change
	-1.46; (-3.16 to -0.40)	-3.19; (-5.12 to -1.02)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm A: Vitamin D3 and Calcium Carbonate Plus EFV/FTC/TDF, Arm B: Vitamin D3 Placebo and Calcium Placebo Plus EFV/FTC/TDF
	Comments	The study was sized to have 80% power to detect a 2 % difference in BMD of the hip from baseline to week 48.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.001
	Comments	2-sided test with type I error rate of 5%, not adjusted for multiple comparisons.
	Method	Stratified Wilcoxon rank sum test
	Comments	Stratified Wilcoxon rank sum test for differences between the two treatment groups, stratified by the screening 25-OH vitamin (<=20 vs. >20 ng/mL)

2. Secondary Outcome

Title	The Percent Change From Baseline in Bone Mineral Density (BMD) at Spine
Description	The percent change from baseline to week 48 in bone mineral density (BMD) at spine as measured by DXA scan
Time Frame	Weeks 0 and 48

Outcome Measure Data

Analysis Population Description

This analysis is intent-to-treat (ITT) which is limited to eligible subjects who have baseline and week 48 follow-up regardless of treatment change or discontinuation.

Arm/Group Title	Arm A: Vitamin D3 and Calcium Carbonate Plus EFV/FTC/TDF	Arm B: Vitamin D3 Placebo and Calcium Placebo Plus EFV/FTC/TDF
Arm/Group Description:	The participants were administered vitamin D3, calcium carbonate and FDC efavirenz/emtricitabine/tenofovir disoproxil fumarate (Atripla). Vitamin D3: One Vitamin D3 4000 IU capsule taken orally once daily with food for 48 weeks. Calcium Carbonate: Calcium carbonate 500 mg tablet taken orally twice daily with food for 48 weeks. Atripla: FDC efavirenz/emtricitabine/tenofovir disoproxil fumarate (EFV/FTC/TDF) 600 mg/200 mg/ 300 mg tablet taken orally once daily at bedtime on an empty stomach.	The participants were administered a placebo for vitamin D3, a placebo for calcium carbonate, and FDC efavirenz/emtricitabine/tenofovir disoproxil fumarate (Atripla). Placebo for vitamin D3: A placebo for vitamin D3 once daily taken orally as one capsule with food for 48 weeks. Placebo for calcium carbonate: A placebo for calcium carbonate twice daily taken orally as one x 0 mg tablets with food for 48 weeks Atripla: FDC efavirenz/emtricitabine/tenofovir disoproxil fumarate (EFV/FTC/TDF) 600 mg/200 mg/ 300 mg tablet taken orally once daily at bedtime on an empty stomach.
Overall Number of Participants Analyzed	67	78
Median (Inter-Quartile Range); Unit of Measure: percentage change
	-1.41; (-3.78 to 0.00)	-2.91; (-4.84 to -1.06)

3. Secondary Outcome

Title	Number of Participants With Primary Adverse Events
Description	Primary adverse events include all SAEs defined according to ICH guidelines and targeted protocol events, which include all diagnoses of hypercalcemia, hypophoatemia, and nephrolithiasis as well as signs and symptoms grade 2 or higher that may be associated with hypercalcemia and all laboratory toxicities grade 2 or higher defined by the 2004 DAIDS grading table
Time Frame	From first study treatment to week 48

Outcome Measure Data

Analysis Population Description

All enrolled subjects including subjects excluded from efficacy analysis due to eligibility violation.

Arm/Group Title	Arm A: Vitamin D3 and Calcium Carbonate Plus EFV/FTC/TDF	Arm B: Vitamin D3 Placebo and Calcium Placebo Plus EFV/FTC/TDF
Arm/Group Description:	The participants were administered vitamin D3, calcium carbonate and FDC efavirenz/emtricitabine/tenofovir disoproxil fumarate (Atripla). Vitamin D3: One Vitamin D3 4000 IU capsule taken orally once daily with food for 48 weeks. Calcium Carbonate: Calcium carbonate 500 mg tablet taken orally twice daily with food for 48 weeks. Atripla: FDC efavirenz/emtricitabine/tenofovir disoproxil fumarate (EFV/FTC/TDF) 600 mg/200 mg/ 300 mg tablet taken orally once daily at bedtime on an empty stomach.	The participants were administered a placebo for vitamin D3, a placebo for calcium carbonate, and FDC efavirenz/emtricitabine/tenofovir disoproxil fumarate (Atripla) Placebo for vitamin D3: A placebo for vitamin D3 once daily taken orally as one capsule with food for 48 weeks. Placebo for calcium carbonate: A placebo for calcium carbonate twice daily taken orally as one x 0 mg tablets with food for 48 weeks Atripla: FDC efavirenz/emtricitabine/tenofovir disoproxil fumarate (EFV/FTC/TDF) 600 mg/200 mg/ 300 mg tablet taken orally once daily at bedtime on an empty stomach.
Overall Number of Participants Analyzed	81	86
Measure Type: Number; Unit of Measure: participants
	50	53

4. Secondary Outcome

Title	The Change in Total 25-OH Vitamin D Level From Baseline to Weeks 24 and 48
Description	Changes in total 25-OH vitamin D from baseline to weeks 24 and 48 ( [week 24-baseline] and [week 48 - baseline], respectively). Total 25-OH vitamin D is the sum of vitamin 25-OH D2 and D3 levels. All 25-OH vitamin D2 or D3 values below the lower limit of 1.25 ng/mL were imputed to 0 ng/mL
Time Frame	Weeks 0, 24, and 48

Outcome Measure Data

Analysis Population Description

Included all available data regardless of treatment change/discontinuation, but was limited to eligible subjects who had both baseline and follow-up data.

n=71 and 74 for changes at week 24, n=65 and 68 for changes at week 48.

Arm/Group Title	Arm A: Vitamin D3 and Calcium Carbonate Plus EFV/FTC/TDF	Arm B: Vitamin D3 Placebo and Calcium Placebo Plus EFV/FTC/TDF
Arm/Group Description:	The participants were administered vitamin D3, calcium carbonate and FDC efavirenz/emtricitabine/tenofovir disoproxil fumarate (Atripla). Vitamin D3: One Vitamin D3 4000 IU capsule taken orally once daily with food for 48 weeks. Calcium Carbonate: Calcium carbonate 500 mg tablet taken orally twice daily with food for 48 weeks. Atripla: FDC efavirenz/emtricitabine/tenofovir disoproxil fumarate (EFV/FTC/TDF) 600 mg/200 mg/ 300 mg tablet taken orally once daily at bedtime on an empty stomach.	The participants were administered a placebo for vitamin D3, a placebo for calcium carbonate, and FDC efavirenz/emtricitabine/tenofovir disoproxil fumarate (Atripla) Placebo for vitamin D3: A placebo for vitamin D3 once daily taken orally as one capsule with food for 48 weeks. Placebo for calcium carbonate: A placebo for calcium carbonate twice daily taken orally as one x 0 mg tablets with food for 48 weeks Atripla: FDC efavirenz/emtricitabine/tenofovir disoproxil fumarate (EFV/FTC/TDF) 600 mg/200 mg/ 300 mg tablet taken orally once daily at bedtime on an empty stomach.
Overall Number of Participants Analyzed	71	74
Median (Inter-Quartile Range); Unit of Measure: ng/mL
change from baseline to week 24	27.5; (15.0 to 38.0)	-0.8; (-5.9 to 4.9)
change from baseline to week 48	24.2; (14.3 to 35.8)	0.6; (-6.1 to 4.3)

5. Secondary Outcome

Title	The Changes From Baseline in IL-6 to Weeks 24 and 48
Description	Interleukin 6 (IL-6) changes from baseline to weeks 24 and 48 ( [week 24-baseline] and [week 48 - baseline], respectively).
Time Frame	Weeks 0, 24 and 48

Outcome Measure Data

Analysis Population Description

Included all available data regardless of treatment change/discontinuation, but was limited to eligible subjects who had both baseline and follow-up data.

n=66 and 68 for changes at week 24, n=58 and 62 for changes at week 48.

Arm/Group Title	Arm A: Vitamin D3 and Calcium Carbonate Plus EFV/FTC/TDF	Arm B: Vitamin D3 Placebo and Calcium Placebo Plus EFV/FTC/TDF
Arm/Group Description:	The participants were administered vitamin D3, calcium carbonate and FDC efavirenz/emtricitabine/tenofovir disoproxil fumarate (Atripla). Vitamin D3: One Vitamin D3 4000 IU capsule taken orally once daily with food for 48 weeks. Calcium Carbonate: Calcium carbonate 500 mg tablet taken orally twice daily with food for 48 weeks. Atripla: FDC efavirenz/emtricitabine/tenofovir disoproxil fumarate (EFV/FTC/TDF) 600 mg/200 mg/ 300 mg tablet taken orally once daily at bedtime on an empty stomach.	The participants were administered a placebo for vitamin D3, a placebo for calcium carbonate, and FDC efavirenz/emtricitabine/tenofovir disoproxil fumarate (Atripla) Placebo for vitamin D3: A placebo for vitamin D3 once daily taken orally as one capsule with food for 48 weeks. Placebo for calcium carbonate: A placebo for calcium carbonate twice daily taken orally as one x 0 mg tablets with food for 48 weeks Atripla: FDC efavirenz/emtricitabine/tenofovir disoproxil fumarate (EFV/FTC/TDF) 600 mg/200 mg/ 300 mg tablet taken orally once daily at bedtime on an empty stomach.
Overall Number of Participants Analyzed	66	68
Median (Inter-Quartile Range); Unit of Measure: log10 pg/mL
change from baseline to week 24	-0.05; (-0.23 to 0.11)	-0.04; (-0.23 to 0.14)
change from baseline to week 48	-0.07; (-0.24 to 0.12)	-0.03; (-0.23 to 0.10)

6. Secondary Outcome

Title	The Changes From Baseline in sCD14 to Weeks 24 and 48
Description	Soluble cluster of differentiation 14 (sCD14) changes from baseline to weeks 24 and 48 ( [week 24-baseline] and [week 48 - baseline], respectively).
Time Frame	Weeks 0, 24 and 48

Outcome Measure Data

Analysis Population Description

Included all available data regardless of treatment change/discontinuation, but was limited to eligible subjects who had both baseline and follow-up data.

n=68 and 68 for changes at week 24, n=62 and 63 for changes at week 48.

Arm/Group Title	Arm A: Vitamin D3 and Calcium Carbonate Plus EFV/FTC/TDF	Arm B: Vitamin D3 Placebo and Calcium Placebo Plus EFV/FTC/TDF
Arm/Group Description:	The participants were administered vitamin D3, calcium carbonate and FDC efavirenz/emtricitabine/tenofovir disoproxil fumarate (Atripla). Vitamin D3: One Vitamin D3 4000 IU capsule taken orally once daily with food for 48 weeks. Calcium Carbonate: Calcium carbonate 500 mg tablet taken orally twice daily with food for 48 weeks. Atripla: FDC efavirenz/emtricitabine/tenofovir disoproxil fumarate (EFV/FTC/TDF) 600 mg/200 mg/ 300 mg tablet taken orally once daily at bedtime on an empty stomach.	The participants were administered a placebo for vitamin D3, a placebo for calcium carbonate, and FDC efavirenz/emtricitabine/tenofovir disoproxil fumarate (Atripla) Placebo for vitamin D3: A placebo for vitamin D3 once daily taken orally as one capsule with food for 48 weeks. Placebo for calcium carbonate: A placebo for calcium carbonate twice daily taken orally as one x 0 mg tablets with food for 48 weeks Atripla: FDC efavirenz/emtricitabine/tenofovir disoproxil fumarate (EFV/FTC/TDF) 600 mg/200 mg/ 300 mg tablet taken orally once daily at bedtime on an empty stomach.
Overall Number of Participants Analyzed	68	68
Median (Inter-Quartile Range); Unit of Measure: log10 ng/mL
change from baseline to week 24	0.02; (-0.08 to 0.15)	0.00; (-0.07 to 0.14)
change from baseline to week 48	0.07; (-0.05 to 0.16)	0.02; (-0.06 to 0.14)

7. Secondary Outcome

Title	The Changes From Baseline in P1NP to Weeks 24 and 48
Description	P1NP (marker of bone formation) changes from baseline to weeks 24 and 48 ( [week 24-baseline] and [week 48 - baseline], respectively).
Time Frame	Weeks 0, 24 and 48

Outcome Measure Data

Analysis Population Description

Included all available data regardless of treatment change/discontinuation, but was limited to eligible subjects who had both baseline and follow-up data.

n=72 and 77 for changes at week 24, n=66 and 72 for changes at week 48.

Arm/Group Title	Arm A: Vitamin D3 and Calcium Carbonate Plus EFV/FTC/TDF	Arm B: Vitamin D3 Placebo and Calcium Placebo Plus EFV/FTC/TDF
Arm/Group Description:	The participants were administered vitamin D3, calcium carbonate and FDC efavirenz/emtricitabine/tenofovir disoproxil fumarate (Atripla). Vitamin D3: One Vitamin D3 4000 IU capsule taken orally once daily with food for 48 weeks. Calcium Carbonate: Calcium carbonate 500 mg tablet taken orally twice daily with food for 48 weeks. Atripla: FDC efavirenz/emtricitabine/tenofovir disoproxil fumarate (EFV/FTC/TDF) 600 mg/200 mg/ 300 mg tablet taken orally once daily at bedtime on an empty stomach.	The participants were administered a placebo for vitamin D3, a placebo for calcium carbonate, and FDC efavirenz/emtricitabine/tenofovir disoproxil fumarate (Atripla) Placebo for vitamin D3: A placebo for vitamin D3 once daily taken orally as one capsule with food for 48 weeks. Placebo for calcium carbonate: A placebo for calcium carbonate twice daily taken orally as one x 0 mg tablets with food for 48 weeks Atripla: FDC efavirenz/emtricitabine/tenofovir disoproxil fumarate (EFV/FTC/TDF) 600 mg/200 mg/ 300 mg tablet taken orally once daily at bedtime on an empty stomach.
Overall Number of Participants Analyzed	72	77
Median (Inter-Quartile Range); Unit of Measure: ng/mL
change from baseline to week 24	11; (2 to 26)	21; (12 to 38)
change from baseline to week 48	15; (0 to 29)	18; (7 to 39)

8. Secondary Outcome

Title	The Changes From Baseline in CTX to Weeks 24 and 48
Description	CTX (marker of bone resorption) changes from baseline to weeks 24 and 48 ( [week 24-baseline] and [week 48 - baseline], respectively).
Time Frame	Weeks 0, 24 and 48

Outcome Measure Data

Analysis Population Description

Included all available data regardless of treatment change/discontinuation, but was limited to eligible subjects who had both baseline and follow-up data.

n=72 and 77 for changes at week 24, n=66 and 72 for changes at week 48.

Arm/Group Title	Arm A: Vitamin D3 and Calcium Carbonate Plus EFV/FTC/TDF	Arm B: Vitamin D3 Placebo and Calcium Placebo Plus EFV/FTC/TDF
Arm/Group Description:	The participants were administered vitamin D3, calcium carbonate and FDC efavirenz/emtricitabine/tenofovir disoproxil fumarate (Atripla). Vitamin D3: One Vitamin D3 4000 IU capsule taken orally once daily with food for 48 weeks. Calcium Carbonate: Calcium carbonate 500 mg tablet taken orally twice daily with food for 48 weeks. Atripla: FDC efavirenz/emtricitabine/tenofovir disoproxil fumarate (EFV/FTC/TDF) 600 mg/200 mg/ 300 mg tablet taken orally once daily at bedtime on an empty stomach.	The participants were administered a placebo for vitamin D3, a placebo for calcium carbonate, and FDC efavirenz/emtricitabine/tenofovir disoproxil fumarate (Atripla) Placebo for vitamin D3: A placebo for vitamin D3 once daily taken orally as one capsule with food for 48 weeks. Placebo for calcium carbonate: A placebo for calcium carbonate twice daily taken orally as one x 0 mg tablets with food for 48 weeks Atripla: FDC efavirenz/emtricitabine/tenofovir disoproxil fumarate (EFV/FTC/TDF) 600 mg/200 mg/ 300 mg tablet taken orally once daily at bedtime on an empty stomach.
Overall Number of Participants Analyzed	72	77
Median (Inter-Quartile Range); Unit of Measure: ng/mL
change from baseline to week 24	0.11; (-0.01 to 0.27)	0.22; (0.11 to 0.35)
change from baseline to week 48	0.10; (-0.04 to 0.25)	0.14; (0.05 to 0.32)

9. Secondary Outcome

Title	The Changes From Baseline in HOMA-IR to Weeks 24 and 48
Description	Homeostatic model assessment insulin resistance (HOMA-IR) changes from baseline to weeks 24 and 48 ( [week 24-baseline] and [week 48 - baseline], respectively).
Time Frame	Weeks 0, 24 and 48

Outcome Measure Data

Analysis Population Description

Included all available data regardless of treatment change/discontinuation, but was limited to eligible subjects who had both baseline and follow-up data.

n=69 and 73 for changes at week 24, n=64 and 69 for changes at week 48.

Arm/Group Title	Arm A: Vitamin D3 and Calcium Carbonate Plus EFV/FTC/TDF	Arm B: Vitamin D3 Placebo and Calcium Placebo Plus EFV/FTC/TDF
Arm/Group Description:	The participants were administered vitamin D3, calcium carbonate and FDC efavirenz/emtricitabine/tenofovir disoproxil fumarate (Atripla). Vitamin D3: One Vitamin D3 4000 IU capsule taken orally once daily with food for 48 weeks. Calcium Carbonate: Calcium carbonate 500 mg tablet taken orally twice daily with food for 48 weeks. Atripla: FDC efavirenz/emtricitabine/tenofovir disoproxil fumarate (EFV/FTC/TDF) 600 mg/200 mg/ 300 mg tablet taken orally once daily at bedtime on an empty stomach.	The participants were administered a placebo for vitamin D3, a placebo for calcium carbonate, and FDC efavirenz/emtricitabine/tenofovir disoproxil fumarate (Atripla) Placebo for vitamin D3: A placebo for vitamin D3 once daily taken orally as one capsule with food for 48 weeks. Placebo for calcium carbonate: A placebo for calcium carbonate twice daily taken orally as one x 0 mg tablets with food for 48 weeks Atripla: FDC efavirenz/emtricitabine/tenofovir disoproxil fumarate (EFV/FTC/TDF) 600 mg/200 mg/ 300 mg tablet taken orally once daily at bedtime on an empty stomach.
Overall Number of Participants Analyzed	69	73
Median (Inter-Quartile Range); Unit of Measure: HOMA-IR
change from baseline to week 24	0.17; (-0.21 to 0.91)	0.39; (-0.11 to 1.15)
change from baseline to week 48	0.13; (-0.26 to 1.11)	0.26; (-0.44 to 0.79)

10. Secondary Outcome

Title	The Changes From Baseline in Fasting Total Cholesterol to Weeks 24 and 48
Description	Fasting total cholesterol changes from baseline to weeks 24 and 48 ( [week 24-baseline] and [week 48 - baseline], respectively).
Time Frame	Weeks 0, 24 and 48

Outcome Measure Data

Analysis Population Description

Included all available data regardless of treatment change/discontinuation, but was limited to eligible subjects who had both baseline and follow-up data.

n=74 and 80 for changes at week 24, n=68 and 73 for changes at week 48.

Arm/Group Title	Arm A: Vitamin D3 and Calcium Carbonate Plus EFV/FTC/TDF	Arm B: Vitamin D3 Placebo and Calcium Placebo Plus EFV/FTC/TDF
Arm/Group Description:	The participants were administered vitamin D3, calcium carbonate and FDC efavirenz/emtricitabine/tenofovir disoproxil fumarate (Atripla). Vitamin D3: One Vitamin D3 4000 IU capsule taken orally once daily with food for 48 weeks. Calcium Carbonate: Calcium carbonate 500 mg tablet taken orally twice daily with food for 48 weeks. Atripla: FDC efavirenz/emtricitabine/tenofovir disoproxil fumarate (EFV/FTC/TDF) 600 mg/200 mg/ 300 mg tablet taken orally once daily at bedtime on an empty stomach.	The participants were administered a placebo for vitamin D3, a placebo for calcium carbonate, and FDC efavirenz/emtricitabine/tenofovir disoproxil fumarate (Atripla) Placebo for vitamin D3: A placebo for vitamin D3 once daily taken orally as one capsule with food for 48 weeks. Placebo for calcium carbonate: A placebo for calcium carbonate twice daily taken orally as one x 0 mg tablets with food for 48 weeks Atripla: FDC efavirenz/emtricitabine/tenofovir disoproxil fumarate (EFV/FTC/TDF) 600 mg/200 mg/ 300 mg tablet taken orally once daily at bedtime on an empty stomach.
Overall Number of Participants Analyzed	74	80
Median (Inter-Quartile Range); Unit of Measure: mg/dL
change from baseline to week 24	11; (-4 to 29)	18; (1 to 31)
change from baseline to week 48	13; (-6 to 28)	14; (-1 to 37)

11. Secondary Outcome

Title	The Changes From Baseline in Fasting LDL to Weeks 24 and 48
Description	Fasting LDL cholesterol changes from baseline to weeks 24 and 48 ( [week 24-baseline] and [week 48 - baseline], respectively).
Time Frame	Weeks 0, 24 and 48

Outcome Measure Data

Analysis Population Description

Included all available data regardless of treatment change/discontinuation, but was limited to eligible subjects who had both baseline and follow-up data.

n=70 and 72 for changes at week 24, n=65 and 67 for changes at week 48.

Arm/Group Title	Arm A: Vitamin D3 and Calcium Carbonate Plus EFV/FTC/TDF	Arm B: Vitamin D3 Placebo and Calcium Placebo Plus EFV/FTC/TDF
Arm/Group Description:	The participants were administered vitamin D3, calcium carbonate and FDC efavirenz/emtricitabine/tenofovir disoproxil fumarate (Atripla). Vitamin D3: One Vitamin D3 4000 IU capsule taken orally once daily with food for 48 weeks. Calcium Carbonate: Calcium carbonate 500 mg tablet taken orally twice daily with food for 48 weeks. Atripla: FDC efavirenz/emtricitabine/tenofovir disoproxil fumarate (EFV/FTC/TDF) 600 mg/200 mg/ 300 mg tablet taken orally once daily at bedtime on an empty stomach.	The participants were administered a placebo for vitamin D3, a placebo for calcium carbonate, and FDC efavirenz/emtricitabine/tenofovir disoproxil fumarate (Atripla) Placebo for vitamin D3: A placebo for vitamin D3 once daily taken orally as one capsule with food for 48 weeks. Placebo for calcium carbonate: A placebo for calcium carbonate twice daily taken orally as one x 0 mg tablets with food for 48 weeks Atripla: FDC efavirenz/emtricitabine/tenofovir disoproxil fumarate (EFV/FTC/TDF) 600 mg/200 mg/ 300 mg tablet taken orally once daily at bedtime on an empty stomach.
Overall Number of Participants Analyzed	70	72
Median (Inter-Quartile Range); Unit of Measure: mg/dL
change from baseline to week 24	0; (-10 to 17)	8; (-11 to 20)
change from baseline to week 48	2; (-9 to 14)	4; (-14 to 27)

12. Secondary Outcome

Title	The Changes From Baseline in Urinary Phosphate Excretion to Weeks 24 and 48
Description	Fractional excretion of phosphate changes from baseline to weeks 24 and 48 ( [week 24-baseline] and [week 48 - baseline], respectively). Fractional Excretion of Phosphate (in %) is defined as: [Urine Phosphate x Serum Creatinine] / [Urine Creatinine x Serum Phosphate] x 100%
Time Frame	Weeks 0, 24 and 48

Outcome Measure Data

Analysis Population Description

Included all available data regardless of treatment change/discontinuation, but was limited to eligible subjects who had both baseline and follow-up data.

n=58 and 70 for changes at week 24, n=59 and 69 for changes at week 48.

Arm/Group Title	Arm A: Vitamin D3 and Calcium Carbonate Plus EFV/FTC/TDF	Arm B: Vitamin D3 Placebo and Calcium Placebo Plus EFV/FTC/TDF
Arm/Group Description:	The participants were administered vitamin D3, calcium carbonate and FDC efavirenz/emtricitabine/tenofovir disoproxil fumarate (Atripla). Vitamin D3: One Vitamin D3 4000 IU capsule taken orally once daily with food for 48 weeks. Calcium Carbonate: Calcium carbonate 500 mg tablet taken orally twice daily with food for 48 weeks. Atripla: FDC efavirenz/emtricitabine/tenofovir disoproxil fumarate (EFV/FTC/TDF) 600 mg/200 mg/ 300 mg tablet taken orally once daily at bedtime on an empty stomach.	The participants were administered a placebo for vitamin D3, a placebo for calcium carbonate, and FDC efavirenz/emtricitabine/tenofovir disoproxil fumarate (Atripla) Placebo for vitamin D3: A placebo for vitamin D3 once daily taken orally as one capsule with food for 48 weeks. Placebo for calcium carbonate: A placebo for calcium carbonate twice daily taken orally as one x 0 mg tablets with food for 48 weeks Atripla: FDC efavirenz/emtricitabine/tenofovir disoproxil fumarate (EFV/FTC/TDF) 600 mg/200 mg/ 300 mg tablet taken orally once daily at bedtime on an empty stomach.
Overall Number of Participants Analyzed	58	70
Median (Inter-Quartile Range); Unit of Measure: percent
change from baseline to week 24	0.7; (-2.4 to 3.1)	0.2; (-1.8 to 3.8)
change from baseline to week 48	0; (-1.8 to 3.7)	0.9; (-1.9 to 4.0)

13. Secondary Outcome

Title	The Changes From Baseline in CD4 to Weeks 4, 12, 24 and 48
Description	Total CD4 count changes from baseline to weeks 4, 12, 24 and 48 [week 4/12/24/48 - baseline].
Time Frame	Weeks 0, 4, 12, 24 and 48

Outcome Measure Data

Analysis Population Description

Included all available data regardless of treatment change/discontinuation, but was limited to eligible subjects who had both baseline and follow-up data.

n=78 and 86 for changes at week 4, n=77 and 85 for changes at week 4, n=76 and 84 for changes at week 24, n=69 and 80 for changes at week 48.

Arm/Group Title	Arm A: Vitamin D3 and Calcium Carbonate Plus EFV/FTC/TDF	Arm B: Vitamin D3 Placebo and Calcium Placebo Plus EFV/FTC/TDF
Arm/Group Description:	The participants were administered vitamin D3, calcium carbonate and FDC efavirenz/emtricitabine/tenofovir disoproxil fumarate (Atripla). Vitamin D3: One Vitamin D3 4000 IU capsule taken orally once daily with food for 48 weeks. Calcium Carbonate: Calcium carbonate 500 mg tablet taken orally twice daily with food for 48 weeks. Atripla: FDC efavirenz/emtricitabine/tenofovir disoproxil fumarate (EFV/FTC/TDF) 600 mg/200 mg/ 300 mg tablet taken orally once daily at bedtime on an empty stomach.	The participants were administered a placebo for vitamin D3, a placebo for calcium carbonate, and FDC efavirenz/emtricitabine/tenofovir disoproxil fumarate (Atripla) Placebo for vitamin D3: A placebo for vitamin D3 once daily taken orally as one capsule with food for 48 weeks. Placebo for calcium carbonate: A placebo for calcium carbonate twice daily taken orally as one x 0 mg tablets with food for 48 weeks Atripla: FDC efavirenz/emtricitabine/tenofovir disoproxil fumarate (EFV/FTC/TDF) 600 mg/200 mg/ 300 mg tablet taken orally once daily at bedtime on an empty stomach.
Overall Number of Participants Analyzed	78	86
Median (Inter-Quartile Range); Unit of Measure: cells/mm^3
change from baseline to week 4	74; (2 to 146)	60; (15 to 102)
change from baseline to week 12	103; (41 to 170)	106; (60 to 216)
change from baseline to week 24	138; (46 to 195)	136; (66 to 219)
change from baseline to week 48	192; (113 to 305)	201; (108 to 292)

14. Secondary Outcome

Title	The Changes From Baseline in iPTH to Weeks 24 and 48
Description	iPTH (Parathyroid Hormone, intact) changes from baseline to weeks 24 and 48 ( [week 24-baseline] and [week 48 - baseline], respectively).
Time Frame	Weeks 0, 24 and 48

Outcome Measure Data

Analysis Population Description

Included all available data regardless of treatment change/discontinuation, but was limited to eligible subjects who had both baseline and follow-up data.

n=72 and 77 for changes at week 24, n=66 and 72 for changes at week 48.

Arm/Group Title	Arm A: Vitamin D3 and Calcium Carbonate Plus EFV/FTC/TDF	Arm B: Vitamin D3 Placebo and Calcium Placebo Plus EFV/FTC/TDF
Arm/Group Description:	The participants were administered vitamin D3, calcium carbonate and FDC efavirenz/emtricitabine/tenofovir disoproxil fumarate (Atripla). Vitamin D3: One Vitamin D3 4000 IU capsule taken orally once daily with food for 48 weeks. Calcium Carbonate: Calcium carbonate 500 mg tablet taken orally twice daily with food for 48 weeks. Atripla: FDC efavirenz/emtricitabine/tenofovir disoproxil fumarate (EFV/FTC/TDF) 600 mg/200 mg/ 300 mg tablet taken orally once daily at bedtime on an empty stomach.	The participants were administered a placebo for vitamin D3, a placebo for calcium carbonate, and FDC efavirenz/emtricitabine/tenofovir disoproxil fumarate (Atripla) Placebo for vitamin D3: A placebo for vitamin D3 once daily taken orally as one capsule with food for 48 weeks. Placebo for calcium carbonate: A placebo for calcium carbonate twice daily taken orally as one x 0 mg tablets with food for 48 weeks Atripla: FDC efavirenz/emtricitabine/tenofovir disoproxil fumarate (EFV/FTC/TDF) 600 mg/200 mg/ 300 mg tablet taken orally once daily at bedtime on an empty stomach.
Overall Number of Participants Analyzed	72	77
Median (Inter-Quartile Range); Unit of Measure: pg/mL
change from baseline to week 24	0.4; (-3.8 to 5.7)	4.2; (-0.8 to 9.3)
change from baseline to week 48	1.1; (-4.0 to 6.1)	5.2; (-0.7 to 12.6)

Adverse Events

Time Frame	From first study treatment to week 48
Adverse Event Reporting Description	Adverse events from patients' first study treatment date to off study date. medDRA version 16.1
Arm/Group Title	Arm A: Vitamin D3 and Calcium Carbonate Plus EFV/FTC/TDF	Arm B: Vitamin D3 Placebo and Calcium Placebo Plus EFV/FTC/TDF
Arm/Group Description	The participants were administered vitamin D3, calcium carbonate and FDC efavirenz/emtricitabine/tenofovir disoproxil fumarate (Atripla). Vitamin D3: One Vitamin D3 4000 IU capsule taken orally once daily with food for 48 weeks. Calcium Carbonate: Calcium carbonate 500 mg tablet taken orally twice daily with food for 48 weeks. Atripla: FDC efavirenz/emtricitabine/tenofovir disoproxil fumarate (EFV/FTC/TDF) 600 mg/200 mg/ 300 mg tablet taken orally once daily at bedtime on an empty stomach.	The participants were administered a placebo for vitamin D3, a placebo for calcium carbonate, and FDC efavirenz/emtricitabine/tenofovir disoproxil fumarate (Atripla). Placebo for vitamin D3: A placebo for vitamin D3 once daily taken orally as one capsule with food for 48 weeks. Placebo for calcium carbonate: A placebo for calcium carbonate twice daily taken orally as one x 0 mg tablets with food for 48 weeks Atripla: FDC efavirenz/emtricitabine/tenofovir disoproxil fumarate (EFV/FTC/TDF) 600 mg/200 mg/ 300 mg tablet taken orally once daily at bedtime on an empty stomach.
All-Cause Mortality
	Arm A: Vitamin D3 and Calcium Carbonate Plus EFV/FTC/TDF	Arm B: Vitamin D3 Placebo and Calcium Placebo Plus EFV/FTC/TDF
	Affected / at Risk (%)	Affected / at Risk (%)
Total	--/--	--/--
Serious Adverse Events
	Arm A: Vitamin D3 and Calcium Carbonate Plus EFV/FTC/TDF	Arm B: Vitamin D3 Placebo and Calcium Placebo Plus EFV/FTC/TDF
	Affected / at Risk (%)	Affected / at Risk (%)
Total	8/81 (9.88%)	7/86 (8.14%)
Gastrointestinal disorders
Mallory-Weiss syndrome † 1	1/81 (1.23%)	0/86 (0.00%)
General disorders
Pyrexia † 1	2/81 (2.47%)	0/86 (0.00%)
Hepatobiliary disorders
Cholecystitis † 1	1/81 (1.23%)	0/86 (0.00%)
Infections and infestations
Gastroenteritis † 1	0/81 (0.00%)	1/86 (1.16%)
Gastroenteritis viral † 1	0/81 (0.00%)	1/86 (1.16%)
Herpes zoster † 1	1/81 (1.23%)	0/86 (0.00%)
Lyme disease † 1	0/81 (0.00%)	1/86 (1.16%)
Meningitis aseptic † 1	1/81 (1.23%)	0/86 (0.00%)
Pneumonia streptococcal † 1	0/81 (0.00%)	1/86 (1.16%)
Wound infection † 1	0/81 (0.00%)	1/86 (1.16%)
Injury, poisoning and procedural complications
Laceration † 1	1/81 (1.23%)	0/86 (0.00%)
Investigations
Aspartate aminotransferase increased † 1	0/81 (0.00%)	1/86 (1.16%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Prostate cancer † 1	1/81 (1.23%)	0/86 (0.00%)
Uterine leiomyoma † 1	1/81 (1.23%)	0/86 (0.00%)
Nervous system disorders
Convulsion † 1	1/81 (1.23%)	0/86 (0.00%)
Psychiatric disorders
Depression † 1	0/81 (0.00%)	1/86 (1.16%)
Depression suicidal † 1	1/81 (1.23%)	0/86 (0.00%)
Suicide attempt † 1	0/81 (0.00%)	1/86 (1.16%)
Renal and urinary disorders
Renal failure † 1	1/81 (1.23%)	0/86 (0.00%)
Respiratory, thoracic and mediastinal disorders
Asthma † 1	0/81 (0.00%)	1/86 (1.16%)
Skin and subcutaneous tissue disorders
Drug reaction with eosinophilia and systemic symptoms † 1	0/81 (0.00%)	1/86 (1.16%)
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA 16.1
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Arm A: Vitamin D3 and Calcium Carbonate Plus EFV/FTC/TDF	Arm B: Vitamin D3 Placebo and Calcium Placebo Plus EFV/FTC/TDF
	Affected / at Risk (%)	Affected / at Risk (%)
Total	60/81 (74.07%)	70/86 (81.40%)
Gastrointestinal disorders
Nausea † 1	5/81 (6.17%)	3/86 (3.49%)
Investigations
Alanine aminotransferase abnormal † 1	5/81 (6.17%)	2/86 (2.33%)
Alanine aminotransferase increased † 1	3/81 (3.70%)	9/86 (10.47%)
Aspartate aminotransferase abnormal † 1	5/81 (6.17%)	3/86 (3.49%)
Aspartate aminotransferase increased † 1	3/81 (3.70%)	9/86 (10.47%)
Blood albumin decreased † 1	5/81 (6.17%)	6/86 (6.98%)
Blood calcium decreased † 1	4/81 (4.94%)	5/86 (5.81%)
Blood cholesterol increased † 1	24/81 (29.63%)	26/86 (30.23%)
Blood glucose decreased † 1	9/81 (11.11%)	19/86 (22.09%)
Blood glucose increased † 1	15/81 (18.52%)	16/86 (18.60%)
Blood phosphorus decreased † 1	22/81 (27.16%)	23/86 (26.74%)
Blood sodium decreased † 1	4/81 (4.94%)	8/86 (9.30%)
Low density lipoprotein increased † 1	15/81 (18.52%)	22/86 (25.58%)
Neutrophil count decreased † 1	3/81 (3.70%)	8/86 (9.30%)
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA 16.1

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

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

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

• Name/Title: ACTG ClinicalTrials.gov Coordinator
• Organization: ACTG Network Coordinating Center, Social and Scientific Systems, Inc.
• Phone: (301) 628-3313
• EMail: ACTGCT.Gov@s-3.com

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

Yin MT, Chan ES, Brown TT, Kinslow J, Martinson J, Landay A, Melbourne KM, Ribaudo HJ, Overton ET; A5280 Study Team. Vitamin D does not modulate immune-mediated bone loss during ART initiation. Antivir Ther. 2019;24(5):355-362. doi: 10.3851/IMP3316.

Yin MT, Chan ES, Brown TT, Tebas P, McComsey GA, Melbourne KM, Napoli A, Hardin WR, Ribaudo HJ, Overton ET; A5280 Study Team. Racial differences in calculated bioavailable vitamin D with vitamin D/calcium supplementation. AIDS. 2017 Nov 13;31(17):2337-2344. doi: 10.1097/QAD.0000000000001621.

Overton ET, Chan ES, Brown TT, Tebas P, McComsey GA, Melbourne KM, Napoli A, Hardin WR, Ribaudo HJ, Yin MT. Vitamin D and Calcium Attenuate Bone Loss With Antiretroviral Therapy Initiation: A Randomized Trial. Ann Intern Med. 2015 Jun 16;162(12):815-24. doi: 10.7326/M14-1409.

• Responsible Party: AIDS Clinical Trials Group
• ClinicalTrials.gov Identifier: NCT01403051
• Other Study ID Numbers: ACTG A5280; 1U01AI068636 ( U.S. NIH Grant/Contract )
• First Submitted: July 25, 2011
• First Posted: July 27, 2011
• Results First Submitted: February 5, 2014
• Results First Posted: March 19, 2014
• Last Update Posted: October 12, 2018