High Dose Vitamin D and Calcium for Bone Health in Indivi... | NCT01403051

ID	Type	Description	Link
1U01AI068636	U.S. NIH Grant/Contract		View source

Status Module

Name	Class
National Institute of Allergy and Infectious Diseases (NIAID)	NIH

Description Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Arm A: EFV/FTC/TDF plus vitamin D3 and calcium carbonate	Experimental	Participants were administered FDC efavirenz/emtricitabine/tenofovir disoproxil fumarate (Atripla), calcium carbonate and vitamin D3 4000 IU.	Drug: EFV/FTC/TDF Drug: Calcium Carbonate Drug: Vitamin D3
Arm B: EFV/FTC/TDF plus vitamin D placebo and calcium placebo	Experimental	Participants were administered FDC efavirenz/emtricitabine/tenofovir disoproxil fumarate (Atripla), a placebo for calcium carbonate, and a placebo for vitamin D3.	Drug: EFV/FTC/TDF Drug: Placebo for calcium carbonate Drug: Placebo for vitamin D3

Interventions

Name	Type	Description	Arm Group Labels	Other Names
EFV/FTC/TDF	Drug	FDC efavirenz/emtricitabine/tenofovir disoproxil fumarate (Atripla) 600 mg/200 mg/ 300 mg tablet taken orally once daily at bedtime on an empty stomach.	Arm A: EFV/FTC/TDF plus vitamin D3 and calcium carbonate

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
The Percent Change From Baseline in Bone Mineral Density (BMD) at Total Hip	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)	Weeks 0 and 48

Secondary Outcomes

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

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

HIV-1 infection
No evidence of any exclusionary resistance mutations based on results from any genotype assay from any laboratory that has a CLIA (Clinical Laboratory Improvement Amendments) certification or its equivalent. Results must be available from testing any time in the past or must be obtained prior to entry and reviewed by the site investigator.
ARV drug-naïve (<=10 days of ART at any time prior to entry) and no ARV drugs taken within the past 30 days.
CD4+ cell count of any value obtained within 90 days prior to study entry at any laboratory that has a CLIA certification or its equivalent.
HIV-1 RNA >1000 copies/mL obtained within 90 days prior to study entry at any laboratory that has a CLIA certification or its equivalent.
Certain laboratory values obtained within 30 days prior to entry (as indicated in section 4.1.6 of the protocol.
Serum calcium < 10.5 mg/dL within 30 days prior to entry.
For women of reproductive potential, negative serum or urine pregnancy test within 48 hours prior to initiating study medications.
Subjects must refrain from participating in a conception process (i.e., active attempt to become pregnant or to impregnate, sperm donation, in vitro fertilization) and if participating in sexual activity that could lead to pregnancy, the subject/partner must use at least two of the reliable forms of contraceptive listed in section 4.1.9 of the protocol.
25-OH vitamin D >=10 ng/mL and <75 ng/mL.
Ability and willingness of subject or legally authorized representative to provide informed consent.

Exclusion Criteria:

Current or prior use of bisphosphonate therapy.
Use of vitamin D supplements greater than 800 IU/day within 30 days prior to entry.
Use of calcium supplements greater than 500 mg/day within 30 days prior to entry.
Known allergy/sensitivity or any hypersensitivity to components of study drugs or their formulations.
Any oral, intravenous, or inhaled steroids within the 30 days prior to enrollment(intranasal steroid use is allowed).
Use of androgenic hormones or growth hormones.
Receipt of systemic cytotoxic chemotherapy within 30 days prior to entry.
Pregnancy or currently breastfeeding.
Documentation of acute opportunistic infections within 30 days prior to entry.
Serious illness requiring systemic treatment and/or hospitalization until subject either completes therapy or is clinically stable on therapy, in the opinion of the site investigator, for at least 7 days prior to entry.
Weight >300 lbs (exceeds weight limit of DXA scanners).
History of nephrolithiasis (kidney stones).
History of osteoporosis (as documented by DXA scan) or fragility fracture.
Clinically active thyroid disease (use of thyroid hormone replacement therapy permitted but TSH must be in normal range).
Current imprisonment or involuntary incarceration in a medical facility for psychiatric illness.
Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements.
Any condition that, in the opinion of the site investigator, would compromise the subject's ability to participate in the study.

Name	Affiliation	Role
Edgar (Turner) Overton, MD	Alabama Therapeutics CRS	Study Chair
Michael T Yin, MD, MS	HIV Prevention & Treatment CRS	Study Chair

Facility	Status	City	State	ZIP	Country	Contacts
Alabama Therapeutics CRS (5801)		Birmingham	Alabama	35294	United States
Usc Crs (1201)

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
31085814	Derived	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.
28832406	Derived	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.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Arm A: Vitamin D3 and Calcium Carbonate Plus EFV/FTC/TDF	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.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Arm/Group Information

ID	Title	Description
BG000	Arm A: Vitamin D3 and Calcium Carbonate Plus EFV/FTC/TDF	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.
BG001	Arm B: Vitamin D3 Placebo and Calcium Placebo Plus EFV/FTC/TDF	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.
BG002	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Categorical

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
<=18 years	BG0000 BG0010 BG0020
Between 18 and 65 years

Age, Continuous

Median

Inter-Quartile Range

years

Title

Denominators

Categories

Title	Measurements
	BG00036(28 to 47) BG00131(25 to 44) BG002

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG0007 BG0019 BG002

Race/Ethnicity, Customized

Number

participants

Title

Denominators

Categories

White Non-Hispanic

Title	Measurements
	BG00028 BG00133 BG002

Region of Enrollment

Number

participants

Title

Denominators

Categories

United States

Title	Measurements
	BG00079 BG00186 BG002

HIV-1 RNA level

Entry HIV-RNA level (log10 copies/mL)

Median

Inter-Quartile Range

log10 copies/mL

Title

Denominators

Categories

Title	Measurements
	BG0004.5(4.1 to 5.1) BG0014.5(4.0 to 5.1)

CD4 count

Entry total CD4 count (cells/mm3)

Median

Inter-Quartile Range

cells/mm3

Title

Denominators

Categories

Title	Measurements
	BG000339(230 to 500) BG001342(232 to 454) BG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

The Percent Change From Baseline in Bone Mineral Density (BMD) at Total Hip

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)

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.

Posted

Median

Inter-Quartile Range

percentage change

Weeks 0 and 48

ID	Title	Description
OG000	Arm A: Vitamin D3 and Calcium Carbonate Plus EFV/FTC/TDF	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.
OG001	Arm B: Vitamin D3 Placebo and Calcium Placebo Plus EFV/FTC/TDF	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.

Units	Counts
Participants	OG00065 OG00177

Title

Denominators

Categories

Title	Measurements
	OG000-1.46(-3.16 to -0.40) OG001-3.19(-5.12 to -1.02)

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	The study was sized to have 80% power to detect a 2 % difference in BMD of the hip from baseline to week 48.	Stratified Wilcoxon rank sum test	Stratified Wilcoxon rank sum test for differences between the two treatment groups, stratified by the screening 25-OH vitamin (<=20 vs. >20 ng/mL)	0.001	2-sided test with type I error rate of 5%, not adjusted for multiple comparisons.													Superiority or Other

Secondary

The Percent Change From Baseline in Bone Mineral Density (BMD) at Spine

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

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.

Posted

Median

Inter-Quartile Range

percentage change

Weeks 0 and 48

ID	Title	Description
OG000	Arm A: Vitamin D3 and Calcium Carbonate Plus EFV/FTC/TDF	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.
OG001	Arm B: Vitamin D3 Placebo and Calcium Placebo Plus EFV/FTC/TDF	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.

Secondary

Number of Participants With Primary Adverse Events

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

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

Posted

Number

participants

From first study treatment to week 48

ID	Title	Description
OG000	Arm A: Vitamin D3 and Calcium Carbonate Plus EFV/FTC/TDF	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.
OG001	Arm B: Vitamin D3 Placebo and Calcium Placebo Plus EFV/FTC/TDF	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.

Secondary

The Change in Total 25-OH Vitamin D Level From Baseline to Weeks 24 and 48

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

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.

Posted

Median

Inter-Quartile Range

ng/mL

Weeks 0, 24, and 48

ID	Title	Description
OG000	Arm A: Vitamin D3 and Calcium Carbonate Plus EFV/FTC/TDF	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.
OG001	Arm B: Vitamin D3 Placebo and Calcium Placebo Plus EFV/FTC/TDF	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.

Secondary

The Changes From Baseline in IL-6 to Weeks 24 and 48

Interleukin 6 (IL-6) changes from baseline to weeks 24 and 48 ( [week 24-baseline] and [week 48 - baseline], respectively).

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.

Posted

Median

Inter-Quartile Range

log10 pg/mL

Weeks 0, 24 and 48

ID	Title	Description
OG000	Arm A: Vitamin D3 and Calcium Carbonate Plus EFV/FTC/TDF	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.
OG001	Arm B: Vitamin D3 Placebo and Calcium Placebo Plus EFV/FTC/TDF	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.

Secondary

The Changes From Baseline in sCD14 to Weeks 24 and 48

Soluble cluster of differentiation 14 (sCD14) changes from baseline to weeks 24 and 48 ( [week 24-baseline] and [week 48 - baseline], respectively).

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.

Posted

Median

Inter-Quartile Range

log10 ng/mL

Weeks 0, 24 and 48

ID	Title	Description
OG000	Arm A: Vitamin D3 and Calcium Carbonate Plus EFV/FTC/TDF	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.
OG001	Arm B: Vitamin D3 Placebo and Calcium Placebo Plus EFV/FTC/TDF	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.

Secondary

The Changes From Baseline in P1NP to Weeks 24 and 48

P1NP (marker of bone formation) changes from baseline to weeks 24 and 48 ( [week 24-baseline] and [week 48 - baseline], respectively).

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.

Posted

Median

Inter-Quartile Range

ng/mL

Weeks 0, 24 and 48

ID	Title	Description
OG000	Arm A: Vitamin D3 and Calcium Carbonate Plus EFV/FTC/TDF	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.
OG001	Arm B: Vitamin D3 Placebo and Calcium Placebo Plus EFV/FTC/TDF	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.

Secondary

The Changes From Baseline in CTX to Weeks 24 and 48

CTX (marker of bone resorption) changes from baseline to weeks 24 and 48 ( [week 24-baseline] and [week 48 - baseline], respectively).

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.

Posted

Median

Inter-Quartile Range

ng/mL

Weeks 0, 24 and 48

ID	Title	Description
OG000	Arm A: Vitamin D3 and Calcium Carbonate Plus EFV/FTC/TDF	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.
OG001	Arm B: Vitamin D3 Placebo and Calcium Placebo Plus EFV/FTC/TDF	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.

Secondary

The Changes From Baseline in HOMA-IR to Weeks 24 and 48

Homeostatic model assessment insulin resistance (HOMA-IR) changes from baseline to weeks 24 and 48 ( [week 24-baseline] and [week 48 - baseline], respectively).

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.

Posted

Median

Inter-Quartile Range

HOMA-IR

Weeks 0, 24 and 48

ID	Title	Description
OG000	Arm A: Vitamin D3 and Calcium Carbonate Plus EFV/FTC/TDF	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.
OG001	Arm B: Vitamin D3 Placebo and Calcium Placebo Plus EFV/FTC/TDF	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.

Secondary

The Changes From Baseline in Fasting Total Cholesterol to Weeks 24 and 48

Fasting total cholesterol changes from baseline to weeks 24 and 48 ( [week 24-baseline] and [week 48 - baseline], respectively).

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.

Posted

Median

Inter-Quartile Range

mg/dL

Weeks 0, 24 and 48

ID	Title	Description
OG000	Arm A: Vitamin D3 and Calcium Carbonate Plus EFV/FTC/TDF	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.
OG001	Arm B: Vitamin D3 Placebo and Calcium Placebo Plus EFV/FTC/TDF	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.

Secondary

The Changes From Baseline in Fasting LDL to Weeks 24 and 48

Fasting LDL cholesterol changes from baseline to weeks 24 and 48 ( [week 24-baseline] and [week 48 - baseline], respectively).

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.

Posted

Median

Inter-Quartile Range

mg/dL

Weeks 0, 24 and 48

ID	Title	Description
OG000	Arm A: Vitamin D3 and Calcium Carbonate Plus EFV/FTC/TDF	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.
OG001	Arm B: Vitamin D3 Placebo and Calcium Placebo Plus EFV/FTC/TDF	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.

Secondary

The Changes From Baseline in Urinary Phosphate Excretion to Weeks 24 and 48

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%

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.

Posted

Median

Inter-Quartile Range

percent

Weeks 0, 24 and 48

ID	Title	Description
OG000	Arm A: Vitamin D3 and Calcium Carbonate Plus EFV/FTC/TDF	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.
OG001	Arm B: Vitamin D3 Placebo and Calcium Placebo Plus EFV/FTC/TDF	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.

Secondary

The Changes From Baseline in CD4 to Weeks 4, 12, 24 and 48

Total CD4 count changes from baseline to weeks 4, 12, 24 and 48 [week 4/12/24/48 - baseline].

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.

Posted

Median

Inter-Quartile Range

cells/mm^3

Weeks 0, 4, 12, 24 and 48

ID	Title	Description
OG000	Arm A: Vitamin D3 and Calcium Carbonate Plus EFV/FTC/TDF	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.
OG001	Arm B: Vitamin D3 Placebo and Calcium Placebo Plus EFV/FTC/TDF	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.

Secondary

The Changes From Baseline in iPTH to Weeks 24 and 48

iPTH (Parathyroid Hormone, intact) changes from baseline to weeks 24 and 48 ( [week 24-baseline] and [week 48 - baseline], respectively).

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.

Posted

Median

Inter-Quartile Range

pg/mL

Weeks 0, 24 and 48

ID	Title	Description
OG000	Arm A: Vitamin D3 and Calcium Carbonate Plus EFV/FTC/TDF	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.
OG001	Arm B: Vitamin D3 Placebo and Calcium Placebo Plus EFV/FTC/TDF	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.

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Arm A: Vitamin D3 and Calcium Carbonate Plus EFV/FTC/TDF	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.			8	81	60	81
EG001	Arm B: Vitamin D3 Placebo and Calcium Placebo Plus EFV/FTC/TDF	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.			7	86	70	86

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Mallory-Weiss syndrome	Gastrointestinal disorders	MedDRA 16.1	Systematic Assessment	EG0001 affected81 at risk EG0010 affected86 at risk
Pyrexia	General disorders	MedDRA 16.1	Systematic Assessment	EG0002 affected81 at risk EG0010 affected86 at risk
Cholecystitis	Hepatobiliary disorders	MedDRA 16.1	Systematic Assessment	EG0001 affected81 at risk EG0010 affected86 at risk
Gastroenteritis	Infections and infestations	MedDRA 16.1	Systematic Assessment	EG0000 affected81 at risk EG0011 affected86 at risk
Gastroenteritis viral	Infections and infestations	MedDRA 16.1	Systematic Assessment	EG0000 affected81 at risk EG0011 affected86 at risk
Herpes zoster	Infections and infestations	MedDRA 16.1	Systematic Assessment	EG0001 affected81 at risk EG0010 affected86 at risk
Lyme disease	Infections and infestations	MedDRA 16.1	Systematic Assessment	EG0000 affected81 at risk EG0011 affected86 at risk
Meningitis aseptic	Infections and infestations	MedDRA 16.1	Systematic Assessment	EG0001 affected81 at risk EG0010 affected86 at risk
Pneumonia streptococcal	Infections and infestations	MedDRA 16.1	Systematic Assessment	EG0000 affected81 at risk EG0011 affected86 at risk
Wound infection	Infections and infestations	MedDRA 16.1	Systematic Assessment	EG0000 affected81 at risk EG0011 affected86 at risk
Laceration	Injury, poisoning and procedural complications	MedDRA 16.1	Systematic Assessment	EG0001 affected81 at risk EG0010 affected86 at risk
Aspartate aminotransferase increased	Investigations	MedDRA 16.1	Systematic Assessment	EG0000 affected81 at risk EG0011 affected86 at risk
Prostate cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 16.1	Systematic Assessment	EG0001 affected81 at risk EG0010 affected86 at risk
Uterine leiomyoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 16.1	Systematic Assessment	EG0001 affected81 at risk EG0010 affected86 at risk
Convulsion	Nervous system disorders	MedDRA 16.1	Systematic Assessment	EG0001 affected81 at risk EG0010 affected86 at risk
Depression	Psychiatric disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected81 at risk EG0011 affected86 at risk
Depression suicidal	Psychiatric disorders	MedDRA 16.1	Systematic Assessment	EG0001 affected81 at risk EG0010 affected86 at risk
Suicide attempt	Psychiatric disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected81 at risk EG0011 affected86 at risk
Renal failure	Renal and urinary disorders	MedDRA 16.1	Systematic Assessment	EG0001 affected81 at risk EG0010 affected86 at risk
Asthma	Respiratory, thoracic and mediastinal disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected81 at risk EG0011 affected86 at risk
Drug reaction with eosinophilia and systemic symptoms	Skin and subcutaneous tissue disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected81 at risk EG0011 affected86 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Nausea	Gastrointestinal disorders	MedDRA 16.1	Systematic Assessment	EG0005 affected81 at risk EG0013 affected86 at risk
Alanine aminotransferase abnormal	Investigations	MedDRA 16.1	Systematic Assessment	EG0005 affected81 at risk EG0012 affected86 at risk
Alanine aminotransferase increased	Investigations	MedDRA 16.1	Systematic Assessment	EG0003 affected81 at risk EG0019 affected86 at risk
Aspartate aminotransferase abnormal	Investigations	MedDRA 16.1	Systematic Assessment	EG0005 affected81 at risk EG0013 affected86 at risk
Aspartate aminotransferase increased	Investigations	MedDRA 16.1	Systematic Assessment	EG0003 affected81 at risk EG0019 affected86 at risk
Blood albumin decreased	Investigations	MedDRA 16.1	Systematic Assessment	EG0005 affected81 at risk EG0016 affected86 at risk
Blood calcium decreased	Investigations	MedDRA 16.1	Systematic Assessment	EG0004 affected81 at risk EG0015 affected86 at risk
Blood cholesterol increased	Investigations	MedDRA 16.1	Systematic Assessment	EG00024 affected81 at risk EG00126 affected86 at risk
Blood glucose decreased	Investigations	MedDRA 16.1	Systematic Assessment	EG0009 affected81 at risk EG00119 affected86 at risk
Blood glucose increased	Investigations	MedDRA 16.1	Systematic Assessment	EG00015 affected81 at risk EG00116 affected86 at risk
Blood phosphorus decreased	Investigations	MedDRA 16.1	Systematic Assessment	EG00022 affected81 at risk EG00123 affected86 at risk
Blood sodium decreased	Investigations	MedDRA 16.1	Systematic Assessment	EG0004 affected81 at risk EG0018 affected86 at risk
Low density lipoprotein increased	Investigations	MedDRA 16.1	Systematic Assessment	EG00015 affected81 at risk EG00122 affected86 at risk
Neutrophil count decreased	Investigations	MedDRA 16.1	Systematic Assessment	EG0003 affected81 at risk EG0018 affected86 at risk

Ancestor Terms

ID	Term
D000068698	Tenofovir
D063065	Organophosphonates
D009943	Organophosphorus Compounds
D009930	Organic Chemicals
D010078	Oxazines
D006573	Heterocyclic Compounds, 1-Ring
D006571	Heterocyclic Compounds
D000068679	Emtricitabine
D003841	Deoxycytidine
D003562	Cytidine
D011741	Pyrimidine Nucleosides
D011743	Pyrimidines
D000225	Adenine
D011687	Purines
D006574	Heterocyclic Compounds, 2-Ring
D000072471	Heterocyclic Compounds, Fused-Ring
D004338	Drug Combinations
D004364	Pharmaceutical Preparations
D017610	Calcium Compounds
D007287	Inorganic Chemicals
D002254	Carbonates
D002255	Carbonic Acid
D017554	Carbon Compounds, Inorganic
D008903	Minerals
D002782	Cholestenes
D002776	Cholestanes
D013256	Steroids
D000072473	Fused-Ring Compounds
D011083	Polycyclic Compounds
D013261	Sterols
D014807	Vitamin D
D012632	Secosteroids
D008563	Membrane Lipids
D008055	Lipids

ID	Term
D000068257	Efavirenz, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination
D002119	Calcium Carbonate
D002762	Cholecalciferol