Safety and Effectiveness of Alendronate for Bone Mineral Density in HIV-infected Children and Adolescents

• ClinicalTrials.gov Identifier: NCT00921557
• Recruitment Status: Completed
• First Posted: June 16, 2009
• Results First Posted: March 28, 2017
• Last Update Posted: July 21, 2017
• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Collaborator: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
• Information provided by (Responsible Party): National Institute of Allergy and Infectious Diseases (NIAID)

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Crossover Assignment; Masking: Double (Participant, Care Provider); Primary Purpose: Treatment
• Condition: HIV Infection
• Interventions: Drug: Alendronate; Drug: Placebo; Dietary Supplement: Calcium carbonate/vitamin D
• Enrollment: 52

Participant Flow

Recruitment Details	Fifty-two (52) study participants were recruited between November 5, 2009 and March 27, 2014, at 10 study sites: 8 in the United States and 2 in Brazil.
Pre-assignment Details	Children and adolescents were randomly assigned to 3 treatment sequence groups. Two participants were enrolled, but because their baseline lumbar spine bone mineral density z-score was greater than -1.5 at their baseline visit, they never started study treatment and were taken off the study.

Arm/Group Title	1A: Alendronate/Alendronate	1B: Alendronate/Placebo	2: Placebo/Alendronate
Arm/Group Description	Participants received alendronate for 96 weeks	Participants received alendronate for 48 weeks followed by placebo for 48 weeks	Participants received placebo for 48 weeks followed by alendronate for 48 weeks
Period Title: Weeks 0-48 (on Study Treatment)
Started	17	17	18
Completed	15 [1]	17 [1]	18 [1]
Not Completed	2	0	0
Reason Not Completed
Baseline lumbar spine > -1.5	2	0	0
[1] Completed 48 weeks
Period Title: Weeks 48-96 (on Study Treatment)
Started	15	17	18
Completed	15	16	17
Not Completed	0	1	1
Reason Not Completed
Site Closure	0	1	0
Became a ward of the state	0	0	1
Period Title: Weeks 96-144 (Off Study Treatment)
Started	15	16	17
Completed	12	15	16
Not Completed	3	1	1
Reason Not Completed
Site closure	1	0	0
Not able to attend clinic	2	1	1

Baseline Characteristics

Arm/Group Title		1A: Alendronate/Alendronate	1B: Alendronate/Placebo	2: Placebo/Alendronate	Total
Arm/Group Description		Participants received alendronate for 96 weeks	Participants received alendronate for 48 weeks followed by placebo for 48 weeks	Participants received placebo for 48 weeks followed by alendronate for 48 weeks	Total of all reporting groups
Overall Number of Baseline Participants		15	17	18	50
Baseline Analysis Population Description		Includes participants who took at least one dose of study treatment (alendronate/placebo)
Age, Continuous; Median (Full Range); Unit of measure: Years
	Number Analyzed	15 participants	17 participants	18 participants	50 participants
		16; (11 to 23)	16; (12 to 23)	16; (11 to 22)	16; (11 to 23)
Age, Customized; Measure Type: Count of Participants; Unit of measure: Participants
11 - < 15 years	Number Analyzed	15 participants	17 participants	18 participants	50 participants
		7 46.7%	4 23.5%	6 33.3%	17 34.0%
15 - < 19 years	Number Analyzed	15 participants	17 participants	18 participants	50 participants
		6 40.0%	9 52.9%	8 44.4%	23 46.0%
>= 19 years	Number Analyzed	15 participants	17 participants	18 participants	50 participants
		2 13.3%	4 23.5%	4 22.2%	10 20.0%
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	15 participants	17 participants	18 participants	50 participants
	Female	5 33.3%	6 35.3%	5 27.8%	16 32.0%
	Male	10 66.7%	11 64.7%	13 72.2%	34 68.0%
Race/Ethnicity, Customized; Measure Type: Count of Participants; Unit of measure: Participants
White non-Hispanic	Number Analyzed	15 participants	17 participants	18 participants	50 participants
		3 20.0%	3 17.6%	1 5.6%	7 14.0%
Black non-Hispanic	Number Analyzed	15 participants	17 participants	18 participants	50 participants
		2 13.3%	4 23.5%	1 5.6%	7 14.0%
Hispanic (regardless of race)	Number Analyzed	15 participants	17 participants	18 participants	50 participants
		10 66.7%	10 58.8%	16 88.9%	36 72.0%
Region of Enrollment; Measure Type: Count of Participants; Unit of measure: Participants
United States	Number Analyzed	15 participants	17 participants	18 participants	50 participants
		6 40.0%	8 47.1%	7 38.9%	21 42.0%
Brazil	Number Analyzed	15 participants	17 participants	18 participants	50 participants
		9 60.0%	9 52.9%	11 61.1%	29 58.0%
Tanner stage [1]; Measure Type: Count of Participants; Unit of measure: Participants
1	Number Analyzed	15 participants	17 participants	18 participants	50 participants
		1 6.7%	0 0.0%	2 11.1%	3 6.0%
2	Number Analyzed	15 participants	17 participants	18 participants	50 participants
		3 20.0%	2 11.8%	2 11.1%	7 14.0%
3	Number Analyzed	15 participants	17 participants	18 participants	50 participants
		5 33.3%	1 5.9%	2 11.1%	8 16.0%
4	Number Analyzed	15 participants	17 participants	18 participants	50 participants
		1 6.7%	8 47.1%	6 33.3%	15 30.0%
5	Number Analyzed	15 participants	17 participants	18 participants	50 participants
		5 33.3%	6 35.3%	6 33.3%	17 34.0%
		[1] Measure Description: Tanner stage represents the extent of physical development in children, adolescents and adults. It is based on external physical characteristics such as the size of breasts, genitals and pubic hair. Before puberty children are Tanner 1. Adults are Tanner 5. Study participants were classified as the most advanced stage of breasts and pubic hair (females) and genitals and pubic hair (males).
Smoker; Measure Type: Count of Participants; Unit of measure: Participants
Yes	Number Analyzed	15 participants	17 participants	18 participants	50 participants
		0 0.0%	2 11.8%	1 5.6%	3 6.0%
No	Number Analyzed	15 participants	17 participants	18 participants	50 participants
		15 100.0%	15 88.2%	17 94.4%	47 94.0%
Bone age [1]; Median (Full Range); Unit of measure: Years
	Number Analyzed	15 participants	16 participants	18 participants	49 participants
		14; (10 to 22)	16; (11 to 23)	15; (11 to 21)	15; (10 to 23)
		[1] Measure Analysis Population Description: Bone age estimates maturity of a child's skeletal system. It was assessed by taking an X-ray of the left wrist, hand, and fingers. the X-ray was compared with images in a standard atlas of bone development, based on data from large numbers of other kids of the same gender and age. One participant did not have bone age measured at entry.
Use of tenofovir [1]; Measure Type: Count of Participants; Unit of measure: Participants
Yes	Number Analyzed	15 participants	17 participants	18 participants	50 participants
		7 46.7%	7 41.2%	9 50.0%	23 46.0%
No	Number Analyzed	15 participants	17 participants	18 participants	50 participants
		8 53.3%	10 58.8%	9 50.0%	27 54.0%
		[1] Measure Description: Tenofovir disoproxil is a drug used to treat HIV
CDC HIV disease category [1]; Measure Type: Count of Participants; Unit of measure: Participants
A/1	Number Analyzed	15 participants	17 participants	18 participants	50 participants
		0 0.0%	1 5.9%	3 16.7%	4 8.0%
B/2	Number Analyzed	15 participants	17 participants	18 participants	50 participants
		2 13.3%	0 0.0%	6 33.3%	8 16.0%
C/3	Number Analyzed	15 participants	17 participants	18 participants	50 participants
		13 86.7%	16 94.1%	9 50.0%	38 76.0%
		[1] Measure Description: Severity of HIV disease was classified using the Centers for Disease Control (CDC) 1993 Revised classification system for HIV infection and expanded surveillance case definition for AIDS among adolescents and adults (https://www.cdc.gov/mmwr/preview/mmwrhtml/00018871.htm). Disease category C/3 is the most advanced.
HIV-1 RNA (copies/ml); Measure Type: Count of Participants; Unit of measure: Participants
<= 400	Number Analyzed	15 participants	17 participants	18 participants	50 participants
		10 66.7%	16 94.1%	15 83.3%	41 82.0%
>400	Number Analyzed	15 participants	17 participants	18 participants	50 participants
		5 33.3%	1 5.9%	3 16.7%	9 18.0%
CD4 cell count (cells/mm^3); Measure Type: Count of Participants; Unit of measure: Participants
200 - <500	Number Analyzed	15 participants	17 participants	18 participants	50 participants
		3 20.0%	3 17.6%	2 11.1%	8 16.0%
500 - < 1000	Number Analyzed	15 participants	17 participants	18 participants	50 participants
		10 66.7%	10 58.8%	10 55.6%	30 60.0%
>= 1000	Number Analyzed	15 participants	17 participants	18 participants	50 participants
		2 13.3%	4 23.5%	6 33.3%	12 24.0%
25-OH Vitamin D (ng/mL); Measure Type: Count of Participants; Unit of measure: Participants
10 - < 20	Number Analyzed	15 participants	17 participants	18 participants	50 participants
		1 6.7%	5 29.4%	0 0.0%	6 12.0%
20 - < 30	Number Analyzed	15 participants	17 participants	18 participants	50 participants
		7 46.7%	8 47.1%	6 33.3%	21 42.0%
>= 30	Number Analyzed	15 participants	17 participants	18 participants	50 participants
		7 46.7%	4 23.5%	12 66.7%	23 46.0%
Lumbar spine BMD (g/cm^2); Median (Full Range); Unit of measure: G/cm^2
	Number Analyzed	15 participants	17 participants	18 participants	50 participants
		0.64; (0.47 to 0.93)	0.73; (0.50 to 0.89)	0.66; (0.50 to 0.88)	0.70; (0.47 to 0.93)
Whole body (with head) BMD (g/cm^2) [1]; Median (Full Range); Unit of measure: G/cm^2
	Number Analyzed	14 participants	16 participants	16 participants	46 participants
		0.87; (0.68 to 1.05)	0.91; (0.62 to 1.08)	0.86; (0.69 to 1.08)	0.87; (0.62 to 1.08)
		[1] Measure Analysis Population Description: Whole body (with head) BMD was missing at entry for some participants because of software problems with the DXA machines.

Outcome Measures

1. Primary Outcome

Title	Percent Change From Baseline to Weeks 24 and 48 in Lumbar Spine BMD
Description	Percent change was calculated as (measurement at time T - measurement at baseline)/measurement at baseline * 100%. Results for Groups 1A and 1B combined as both were on alendronate for the first 48 weeks.
Time Frame	Weeks 0, 24 and 48

Outcome Measure Data

Analysis Population Description

Includes all participants who started study treatment

Arm/Group Title	1: Alendronate	2: Placebo
Arm/Group Description:	Participants received alendronate for 48 weeks	Participants received placebo for 48 weeks
Overall Number of Participants Analyzed	32	18
Median (95% Confidence Interval); Unit of Measure: Percent change from baseline
Week 24	14.4; (8.8 to 19.4)	5.5; (1.2 to 7.6)
Week 48	15.9; (9.2 to 25.3)	7.1; (4.9 to 8.9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	1: Alendronate, 2: Placebo
	Comments	Comparison of percent change from baseline to week 24
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	Not adjusted for multiple comparisons.
	Method	Wilcoxon (Mann-Whitney)
	Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	1: Alendronate, 2: Placebo
	Comments	Comparison of percent change from baseline to week 48
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	Not adjusted for multiple comparisons
	Method	Wilcoxon (Mann-Whitney)
	Comments	[Not Specified]

2. Primary Outcome

Title	Percentage of Participants Developing New Signs, Symptoms, Hematology or Chemistry Laboratory Values Greater Than or Equal to Grade 3 or New Cases of Jaw Osteonecrosis, Atrial Fibrillation, or Non-healing Fractures
Description	Signs, symptoms, and laboratory values were graded using the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0 (December 2004). Results for Groups 1A and 1B were combined as both were on alendronate for the first 48 weeks.
Time Frame	Week 0 to 48

Outcome Measure Data

Analysis Population Description

All participants who started study treatment

Arm/Group Title	1: Alendronate	2: Placebo
Arm/Group Description:	Participants received alendronate for 48 weeks	Participants received placebo for 48 weeks
Overall Number of Participants Analyzed	32	18
Measure Type: Count of Participants; Unit of Measure: Participants
	5 15.6%	2 11.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	1: Alendronate, 2: Placebo
	Comments	Comparison of percentage of participants experiencing primary safety outcome
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	>0.99
	Comments	Not adjusted for multiple comparisons
	Method	Fisher Exact
	Comments	[Not Specified]

3. Secondary Outcome

Title	Percent Change From Baseline to Weeks 24 and 48 in Whole Body (With Head) BMD
Description	Percent change was calculated as (measurement at time T - measurement at baseline)/measurement at baseline * 100%. Results for Groups 1A and 1B were combined as both were on alendronate for the first 48 weeks.
Time Frame	Weeks 0, 24 and 48

Outcome Measure Data

Analysis Population Description

Participants who started treatment and had Whole Body (with head) BMD available at week 0

Arm/Group Title		1: Alendronate	2: Placebo
Arm/Group Description:		Participants received alendronate for 48 weeks	Participants received placebo for 48 weeks
Overall Number of Participants Analyzed		30	16
Median (95% Confidence Interval); Unit of Measure: Percent change from baseline
Week 24	Number Analyzed	30 participants	16 participants
		5.5; (3.7 to 8.1)	0.3; (-0.5 to 3.6)
Week 48	Number Analyzed	29 participants	16 participants
		10.7; (6.0 to 16.2)	5.2; (1.6 to 8.5)

4. Secondary Outcome

Title	Percent Change From Baseline to Week 96 in Lumbar Spine BMD
Description	Percent change was calculated as (measurement at week 96 - measurement at baseline)/measurement at baseline * 100%. Includes Groups 1A and 1B only.
Time Frame	Weeks 0 and 96

Outcome Measure Data

Analysis Population Description

Includes all participants who started study treatment and had measurements available at weeks 0 and 96

Arm/Group Title	1A: Alendronate/Alendronate	1B: Alendronate/Placebo
Arm/Group Description:	Participants received alendronate for 96 weeks	Participants received alendronate for 48 weeks followed by placebo for 48 weeks
Overall Number of Participants Analyzed	14	16
Median (95% Confidence Interval); Unit of Measure: Percent change from baseline
	24.9; (11.1 to 69.8)	14.8; (11.4 to 32.6)

5. Secondary Outcome

Title	Percent Change From Baseline to Week 96 in Whole Body (With Head) BMD
Description	Percent change was calculated as (measurement at week 96 - measurement at baseline)/measurement at baseline * 100%. Includes Groups 1A and 1B only.
Time Frame	Weeks 0 and 96

Outcome Measure Data

Analysis Population Description

Includes all participants who started study treatment and had measurements available at weeks 0 and 96

Arm/Group Title	1A: Alendronate/Alendronate	1B: Alendronate/Placebo
Arm/Group Description:	Participants received alendronate for 96 weeks	Participants received alendronate for 48 weeks followed by placebo for 48 weeks
Overall Number of Participants Analyzed	12	14
Median (95% Confidence Interval); Unit of Measure: Percent change from baseline
	19.6; (7.7 to 30.4)	10.3; (5.1 to 24.9)

6. Secondary Outcome

Title	Safety as Measured by the Incidence of New Signs, Symptoms, Hematology or Chemistry Laboratory Values Greater Than or Equal to Grade 3 or New Cases of Jaw Osteonecrosis, Atrial Fibrillation, or Non-healing Fractures
Description	Signs, symptoms, and laboratory values were graded using the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0 (December 2004).
Time Frame	Weeks 0 to 144

Outcome Measure Data

Analysis Population Description

All participants who started treatment

Arm/Group Title		1A: Alendronate/Alendronate	1B: Alendronate/Placebo	2: Placebo/Alendronate
Arm/Group Description:		Participants received alendronate for 96 weeks	Participants received alendronate for 48 weeks followed by placebo for 48 weeks	Participants received placebo for 48 weeks followed by alendronate for 48 weeks
Overall Number of Participants Analyzed		15	17	18
Measure Type: Count of Participants; Unit of Measure: Participants
Week 0 to 48	Number Analyzed	15 participants	17 participants	18 participants
		2 13.3%	3 17.6%	2 11.1%
Week 48 to 96	Number Analyzed	15 participants	17 participants	18 participants
		1 6.7%	3 17.6%	2 11.1%
Week 96 to 144	Number Analyzed	15 participants	16 participants	17 participants
		3 20.0%	4 25.0%	3 17.6%

7. Secondary Outcome

Title	Effect of Other Known Bone Mineral Determinants (Age, Gender, Race/Ethnicity, Steroid Use, Depo-Provera, Tenofovir, Pubertal Stage, Bone Age, Vitamin D Status) and Inflammatory Cytokine Levels on Changes in Lumbar Spine BMD
Description	A slope was fit for each participant to their percent change [(measurement at time T - measurement at baseline)/measurement at baseline)*100%] in lumbar spine BMD from baseline. Results represent average changes in lumbar spine BMD over one year. Results are summarized for age, gender, ethnicity, tenofovir use, Tanner stage, bone age and vitamin D level. Only one participant was on steroids and none were using Dep-Provera. Inflammatory cytokine levels were not assayed. Results were combined for Groups 1A and 1B as both were on alendronate for the first 48 weeks.
Time Frame	Weeks 0, 24 and 48

Outcome Measure Data

Analysis Population Description

Participants who started study treatment

Arm/Group Title		1: Alendronate	2: Placebo
Arm/Group Description:		Participants received alendronate for 48 weeks	Participants received placebo for 48 weeks
Overall Number of Participants Analyzed		32	18
Mean (95% Confidence Interval); Unit of Measure: percentage of baseline
Male	Number Analyzed	21 participants	13 participants
		20.3; (13.0 to 27.6)	6.8; (4.7 to 8.8)
Female	Number Analyzed	11 participants	5 participants
		25.4; (13.3 to 37.5)	9.4; (-0.1 to 18.9)
Non-hispanic	Number Analyzed	12 participants	2 participants
		19.4; (7.6 to 31.1)	4.8; (-1.4 to 11.1)
Hispanic	Number Analyzed	20 participants	16 participants
		23.6; (16.3 to 31.0)	7.8; (5.2 to 10.5)
11 - < 15 years	Number Analyzed	11 participants	6 participants
		37.1; (27.7 to 46.5)	10.6; (5.6 to 15.7)
15 - < 19 years	Number Analyzed	15 participants	8 participants
		16.5; (9.6 to 23.4)	8.0; (5.8 to 10.1)
>= 19 years	Number Analyzed	6 participants	4 participants
		8.1; (-0.7 to 16.9)	1.9; (-4.4 to 8.2)
On Tenofovir	Number Analyzed	14 participants	9 participants
		24.8; (15.1 to 34.5)	6.8; (3.6 to 10.0)
Not on Tenofovir	Number Analyzed	18 participants	9 participants
		19.9; (11.6 to 28.2)	8.2; (3.9 to 12.5)
25-OH Vit D<30 ng/ml	Number Analyzed	21 participants	6 participants
		22.0; (13.5 to 30.4)	6.8; (1.9 to 11.7)
25-0H Vit D>=30 ng/ml	Number Analyzed	11 participants	12 participants
		22.1; (13.5 to 30.8)	7.8; (4.6 to 11.0)
Bone age < 15 years	Number Analyzed	12 participants	9 participants
		36.0; (28.1 to 43.9)	10.0; (6.9 to 13.0)
Bone age>=15 years	Number Analyzed	19 participants	9 participants
		11.3; (7.6 to 15.1)	5.0; (1.6 to 8.4)
Tanner stage <= 3	Number Analyzed	12 participants	6 participants
		33.0; (22.7 to 43.3)	10.6; (5.6 to 15.7)
Tanner stage >= 4	Number Analyzed	20 participants	12 participants
		15.4; (9.2 to 21.6)	5.9; (3.3 to 8.6)

8. Secondary Outcome

Title	Effect of Other Known Bone Mineral Determinants (Age, Gender, Race/Ethnicity, Steroid Use, Depo-Provera, Tenofovir, Pubertal Stage, Bone Age, Vitamin D Status) and Inflammatory Cytokine Levels on Changes in Whole Body (With Head) BMD.
Description	A slope was fit for each participant to their percent change [(measurement at time T - measurement at baseline)/measurement at baseline)*100%] in whole body (with head) BMD from baseline. Results represent average changes in whole body (with head) BMD over one year. Results are summarized for age, gender, ethnicity, tenofovir use, Tanner stage, bone age and vitamin D level. Only one participant was on steroids and none were using Dep-Provera. Inflammatory cytokine levels were not assayed. Results were combined for Groups 1A and 1B as both were on alendronate for the first 48 weeks.
Time Frame	Weeks 0, 24 and 48

Outcome Measure Data

Analysis Population Description

Participants who started study treatment and had Whole Body (with head) available at week 0

Arm/Group Title		1: Alendronate	2: Placebo
Arm/Group Description:		Participants received alendronate for 48 weeks	Participants received placebo for 48 weeks
Overall Number of Participants Analyzed		30	16
Mean (95% Confidence Interval); Unit of Measure: percentage of baseline
Male	Number Analyzed	20 participants	11 participants
		11.4; (7.4 to 15.3)	4.1; (1.1 to 7.1)
Female	Number Analyzed	10 participants	5 participants
		14.0; (6.0 to 22.0)	8.2; (1.6 to 14.7)
Non-Hispanic	Number Analyzed	12 participants	2 participants
		9.8; (2.7 to 17.0)	0.3; (-4.4 to 4.9)
Hispanic	Number Analyzed	18 participants	14 participants
		13.9; (10.0 to 17.7)	6.1; (3.3 to 8.9)
11 - < 15 years	Number Analyzed	10 participants	6 participants
		19.2; (12.9 to 25.5)	8.0; (2.9 to 13.2)
15 - < 19 years	Number Analyzed	14 participants	6 participants
		10.5; (6.1 to 14.9)	6.5; (3.0 to 10.0)
>= 19 years	Number Analyzed	6 participants	4 participants
		4.7; (-2.0 to 11.4)	-0.3; (-3.8 to 3.2)
On tenofovir	Number Analyzed	12 participants	9 participants
		13.2; (7.6 to 18.8)	5.0; (1.5 to 8.6)
Not on tenofovir	Number Analyzed	18 participants	7 participants
		11.6; (6.7 to 16.5)	5.8; (0.5 to 11.2)
25-0H Vit D<30 ng/ml	Number Analyzed	19 participants	5 participants
		10.6; (5.6 to 15.6)	5.8; (-2.7 to 14.3)
25-0H Vit D>=30 ng/ml	Number Analyzed	11 participants	11 participants
		15.1; (10.6 to 19.5)	5.2; (2.3 to 8.0)
Bone age < 15 years	Number Analyzed	10 participants	8 participants
		19.0; (14.7 to 23.3)	8.4; (4.7 to 12.1)
Bone age >=15 years	Number Analyzed	19 participants	8 participants
		7.7; (4.1 to 11.2)	2.3; (-0.6 to 5.2)
Tanner stage <= 3	Number Analyzed	10 participants	6 participants
		18.0; (10.5 to 25.5)	8.0; (2.9 to 13.2)
Tanner stage >= 4	Number Analyzed	20 participants	10 participants
		9.4; (5.9 to 12.8)	3.8; (0.6 to 7.0)

9. Secondary Outcome

Title	Percent Change From Week 48 to Week 96 (Group 1B), Week 48 to Week 144 (Group 1B), and Week 96 to 144 (Group 2) in Lumbar Spine BMD
Description	Percent change was calculated as (measurement at time T2 - measurement at time T1)/measurement at Time T1 * 100%.
Time Frame	Weeks 48, 96 and 144

Outcome Measure Data

Analysis Population Description

All participants who started study treatment and had measurements available at the two time points of interest

Arm/Group Title	1B: Alendronate/Placebo (48 Week Change)	2: Placebo/Alendronate (48 Week Change)	1B: Alendronate/Placebo (96 Week Change)
Arm/Group Description:	Participants received alendronate for 48 weeks followed by placebo for 48 weeks.	Participants received placebo for 48 weeks followed by alendronate for 48 weeks	Participants received alendronate for 48 weeks followed by placebo for 48 weeks.
Overall Number of Participants Analyzed	15	15	15
Median (95% Confidence Interval); Unit of Measure: Percent change
	0.9; (-1.1 to 6.4)	2.0; (-0.6 to 4.6)	1.7; (-1.0 to 6.1)

10. Secondary Outcome

Title	Percent Change From Week 48 to Week 96 (Group 1B), Week 48 to Week 144 (Group 1B), and Week 96 to 144 (Group 2) in Whole Body (With Head) BMD
Description	Percent change was calculated as (measurement at time T2 - measurement at time T2)/measurement at time T1 * 100%.
Time Frame	Weeks 48, 96 and 144

Outcome Measure Data

Analysis Population Description

All participants who started study treatment and had measurements available at both time points.

Arm/Group Title	1B: Alendronate/Placebo (48 Week Change)	2: Placebo/Alendronate (48 Week Change)	1B: Alendronate/Placebo (96 Week Change)
Arm/Group Description:	Participants received alendronate for 48 weeks followed by placebo for 48 weeks.	Participants received placebo for 48 weeks followed by alendronate for 48 weeks	Participants received alendronate for 48 weeks followed by placebo for 48 weeks.
Overall Number of Participants Analyzed	15	13	15
Median (95% Confidence Interval); Unit of Measure: Percent change
	0.8; (-1.9 to 3.1)	0.5; (-0.4 to 2.1)	0.9; (0.0 to 5.9)

11. Secondary Outcome

Title	Change From Baseline to Week 48 in Bone Marker Turnover
Description	Outcome measure required additional funding for laboratory testing which was not available, so this outcome is not reported.
Time Frame	Weeks 0 and 48

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	1A: Alendronate/Alendronate	1B: Alendronate/Placebo	2: Placebo/Alendronate
Arm/Group Description:	Participants received alendronate for 96 weeks	Participants received alendronate for 48 weeks followed by placebo for 48 weeks	Participants received placebo for 48 weeks followed by alendronate for 48 weeks
Overall Number of Participants Analyzed	0	0	0

No data displayed because Outcome Measure has zero total analyzed.

12. Secondary Outcome

Title	Correlation of Changes in Bone Marker Turnover With Changes in Lumbar Spine and Whole Body (With Head) BMD
Description	Outcome measure required additional funding for laboratory testing which was not available, so this outcome is not reported.
Time Frame	Weeks 0 and 48

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	1A: Alendronate/Alendronate	1B: Alendronate/Placebo	2: Placebo/Alendronate
Arm/Group Description:	Participants received alendronate for 96 weeks	Participants received alendronate for 48 weeks followed by placebo for 48 weeks	Participants received placebo for 48 weeks followed by alendronate for 48 weeks
Overall Number of Participants Analyzed	0	0	0

No data displayed because Outcome Measure has zero total analyzed.

13. Secondary Outcome

Title	Change From Baseline to Week 48 in Receptor Activator of Nuclear Factor Kappa-B Ligand/Osteoprotegerin (RANKL/OPG) Ratio
Description	Outcome measure required additional funding for laboratory testing which was not available, so this outcome is not reported.
Time Frame	Weeks 0 and 48

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	1A: Alendronate/Alendronate	1B: Alendronate/Placebo	2: Placebo/Alendronate
Arm/Group Description:	Participants received alendronate for 96 weeks	Participants received alendronate for 48 weeks followed by placebo for 48 weeks	Participants received placebo for 48 weeks followed by alendronate for 48 weeks
Overall Number of Participants Analyzed	0	0	0

No data displayed because Outcome Measure has zero total analyzed.

14. Secondary Outcome

Title	Correlation of Changes in RANKL/OPG Ratio With Changes in Lumbar Spine and Whole Body (With Head) BMD
Description	Outcome measure required additional funding for laboratory testing which was not available, so this outcome is not reported.
Time Frame	Weeks 0 and 48

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	1A: Alendronate/Alendronate	1B: Alendronate/Placebo	2: Placebo/Alendronate
Arm/Group Description:	Participants received alendronate for 96 weeks	Participants received alendronate for 48 weeks followed by placebo for 48 weeks	Participants received placebo for 48 weeks followed by alendronate for 48 weeks
Overall Number of Participants Analyzed	0	0	0

No data displayed because Outcome Measure has zero total analyzed.

15. Secondary Outcome

Title	Change From Baseline to Week 48 in Central Fat Content
Description	Outcome measure required additional funding for laboratory testing which was not available, so this outcome is not reported.
Time Frame	Weeks 0 and 48

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	1A: Alendronate/Alendronate	1B: Alendronate/Placebo	2: Placebo/Alendronate
Arm/Group Description:	Participants received alendronate for 96 weeks	Participants received alendronate for 48 weeks followed by placebo for 48 weeks	Participants received placebo for 48 weeks followed by alendronate for 48 weeks
Overall Number of Participants Analyzed	0	0	0

No data displayed because Outcome Measure has zero total analyzed.

16. Secondary Outcome

Title	Correlation of Changes in Central Fat Content With Changes in Lumbar Spine and Whole Body (With Head) BMD
Description	Outcome measure required additional funding for laboratory testing which was not available, so this outcome is not reported.
Time Frame	Weeks 0 and 48

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	1A: Alendronate/Alendronate	1B: Alendronate/Placebo	2: Placebo/Alendronate
Arm/Group Description:	Participants received alendronate for 96 weeks	Participants received alendronate for 48 weeks followed by placebo for 48 weeks	Participants received placebo for 48 weeks followed by alendronate for 48 weeks
Overall Number of Participants Analyzed	0	0	0

No data displayed because Outcome Measure has zero total analyzed.

17. Secondary Outcome

Title	Percent of Participants With HIV-1 RNA <= 400 Copies/ml
Time Frame	Weeks 0, 48, 96 and 144

Outcome Measure Data

Analysis Population Description

Participants who started study treatment.

Arm/Group Title		1A: Alendronate/Alendronate	1B: Alendronate/Placebo	2: Placebo/Alendronate
Arm/Group Description:		Participants received alendronate for 96 weeks	Participants received alendronate for 48 weeks followed by placebo for 48 weeks	Participants received placebo for 48 weeks followed by alendronate for 48 weeks
Overall Number of Participants Analyzed		15	17	18
Measure Type: Count of Participants; Unit of Measure: Participants
Week 0	Number Analyzed	15 participants	17 participants	18 participants
		10 66.7%	16 94.1%	15 83.3%
Week 48	Number Analyzed	15 participants	17 participants	16 participants
		10 66.7%	16 94.1%	14 87.5%
Week 96	Number Analyzed	14 participants	15 participants	17 participants
		12 85.7%	12 80.0%	13 76.5%
Week 144	Number Analyzed	12 participants	14 participants	16 participants
		10 83.3%	10 71.4%	10 62.5%

18. Secondary Outcome

Title	Change in CD4 Percent From Baseline
Description	Change in percentage of lymphocytes that are CD4 cells calculated as measurement at each time point minus baseline measurement
Time Frame	Weeks 0, 48, 96 and 144

Outcome Measure Data

Analysis Population Description

Participants who started study treatment and had CD4 percent available at week 0.

Arm/Group Title		1A: Alendronate/Alendronate	1B: Alendronate/Placebo	2: Placebo/Alendronate
Arm/Group Description:		Participants received alendronate for 96 weeks	Participants received alendronate for 48 weeks followed by placebo for 48 weeks	Participants received placebo for 48 weeks followed by alendronate for 48 weeks
Overall Number of Participants Analyzed		15	17	18
Median (95% Confidence Interval); Unit of Measure: percent of lymphocytes that are CD4 cell
Week 48 - Week 0	Number Analyzed	15 participants	17 participants	17 participants
		0; (-3 to 4)	1; (-2 to 3)	1; (-2 to 4)
Week 96 - Week 0	Number Analyzed	14 participants	15 participants	17 participants
		0; (-5 to 4)	-1; (-3 to 3)	2; (-4 to 3)
Week 144 - Week 0	Number Analyzed	12 participants	14 participants	16 participants
		1; (-9 to 4)	-1; (-3 to 4)	-4; (-5 to 8)

19. Secondary Outcome

Title	Change in Centers for Disease Control (CDC) HIV Disease Category
Description	Percentage of participants advancing in CDC HIV disease category from baseline throughout study follow-up
Time Frame	Weeks 144

Outcome Measure Data

Analysis Population Description

Participants who started study treatment.

Arm/Group Title		1A: Alendronate/Alendronate	1B: Alendronate/Placebo	2: Placebo/Alendronate
Arm/Group Description:		Participants received alendronate for 96 weeks	Participants received alendronate for 48 weeks followed by placebo for 48 weeks	Participants received placebo for 48 weeks followed by alendronate for 48 weeks
Overall Number of Participants Analyzed		15	17	18
Measure Type: Count of Participants; Unit of Measure: Participants
Week 0 to 48	Number Analyzed	15 participants	17 participants	18 participants
		1 6.7%	0 0.0%	0 0.0%
Week 48 to 96	Number Analyzed	15 participants	17 participants	18 participants
		0 0.0%	1 5.9%	0 0.0%
Week 96 to 144	Number Analyzed	15 participants	16 participants	17 participants
		0 0.0%	0 0.0%	0 0.0%

20. Secondary Outcome

Title	Percent of Participants With Detectable Urinary Alendronate
Description	Outcome measure required additional funding for laboratory testing which was not available, so this outcome is not reported.
Time Frame	Weeks 48, 96 and 144

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	1A: Alendronate/Alendronate	1B: Alendronate/Placebo	2: Placebo/Alendronate
Arm/Group Description:	Participants received alendronate for 96 weeks	Participants received alendronate for 48 weeks followed by placebo for 48 weeks	Participants received placebo for 48 weeks followed by alendronate for 48 weeks
Overall Number of Participants Analyzed	0	0	0

No data displayed because Outcome Measure has zero total analyzed.

Adverse Events

Time Frame	From first dose of study treatment to end of follow-up (144 weeks)
Adverse Event Reporting Description	Expedited adverse event (EAE) reporting followed the DAIDS EAE Manual under the SAE Reporting Category and including fetal losses. Events were graded (1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=death) according to the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0, Clarification Aug 2009. Reports are summarized by randomized arm for consistency with outcomes and because effects of alendronate can continue for months after stopping the drug.
Arm/Group Title	1A: Alendronate/Alendronate	1B: Alendronate/Placebo	2: Placebo/Alendronate
Arm/Group Description	Participants received alendronate for 48 weeks	Participants received alendronate for 48 weeks followed by placebo for 48 weeks	Participants received placebo for 48 weeks followed by alendronate for 48 weeks
All-Cause Mortality
	1A: Alendronate/Alendronate	1B: Alendronate/Placebo	2: Placebo/Alendronate
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/15 (0.00%)	0/17 (0.00%)	0/18 (0.00%)
Serious Adverse Events
	1A: Alendronate/Alendronate	1B: Alendronate/Placebo	2: Placebo/Alendronate
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	2/15 (13.33%)	2/17 (11.76%)	3/18 (16.67%)
Blood and lymphatic system disorders
Neutropenia † 1	0/15 (0.00%)	0/17 (0.00%)	1/18 (5.56%)
Infections and infestations
Pneumonia † 1	0/15 (0.00%)	1/17 (5.88%)	0/18 (0.00%)
Pneumonia bacterial † 1	0/15 (0.00%)	1/17 (5.88%)	0/18 (0.00%)
Tuberculosis † 1	0/15 (0.00%)	0/17 (0.00%)	1/18 (5.56%)
Musculoskeletal and connective tissue disorders
Arthritis † 1	1/15 (6.67%)	0/17 (0.00%)	0/18 (0.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Burkitt's lymphoma † 1	0/15 (0.00%)	0/17 (0.00%)	1/18 (5.56%)
Nervous system disorders
Epilepsy † 1	1/15 (6.67%)	0/17 (0.00%)	0/18 (0.00%)
1 Term from vocabulary, MedDRA 19.1; † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	1A: Alendronate/Alendronate	1B: Alendronate/Placebo	2: Placebo/Alendronate
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	15/15 (100.00%)	17/17 (100.00%)	18/18 (100.00%)
Blood and lymphatic system disorders
Lymph node pain † 1	0/15 (0.00%)	0/17 (0.00%)	1/18 (5.56%)
Lymphadenitis † 1	0/15 (0.00%)	1/17 (5.88%)	0/18 (0.00%)
Cardiac disorders
Bradycardia † 1	0/15 (0.00%)	1/17 (5.88%)	1/18 (5.56%)
Left ventricular hypertrophy † 1	1/15 (6.67%)	0/17 (0.00%)	0/18 (0.00%)
Palpitations † 1	1/15 (6.67%)	0/17 (0.00%)	0/18 (0.00%)
Sinus bradycardia † 1	0/15 (0.00%)	0/17 (0.00%)	1/18 (5.56%)
Tachycardia † 1	0/15 (0.00%)	0/17 (0.00%)	2/18 (11.11%)
Ventricular extrasystoles † 1	1/15 (6.67%)	0/17 (0.00%)	0/18 (0.00%)
Ear and labyrinth disorders
Deafness † 1	1/15 (6.67%)	0/17 (0.00%)	0/18 (0.00%)
Ear congestion † 1	0/15 (0.00%)	1/17 (5.88%)	0/18 (0.00%)
Ear pain † 1	0/15 (0.00%)	2/17 (11.76%)	0/18 (0.00%)
Otorrhoea † 1	0/15 (0.00%)	1/17 (5.88%)	0/18 (0.00%)
Endocrine disorders
Hypothyroidism † 1	0/15 (0.00%)	0/17 (0.00%)	1/18 (5.56%)
Eye disorders
Conjunctival hyperaemia † 1	0/15 (0.00%)	0/17 (0.00%)	1/18 (5.56%)
Eye pain † 1	1/15 (6.67%)	1/17 (5.88%)	1/18 (5.56%)
Myopia † 1	0/15 (0.00%)	1/17 (5.88%)	0/18 (0.00%)
Vision blurred † 1	1/15 (6.67%)	0/17 (0.00%)	0/18 (0.00%)
Gastrointestinal disorders
Abdominal discomfort † 1	0/15 (0.00%)	1/17 (5.88%)	0/18 (0.00%)
Abdominal pain † 1	3/15 (20.00%)	1/17 (5.88%)	2/18 (11.11%)
Abdominal pain lower † 1	0/15 (0.00%)	1/17 (5.88%)	0/18 (0.00%)
Abdominal pain upper † 1	0/15 (0.00%)	0/17 (0.00%)	1/18 (5.56%)
Aphthous ulcer † 1	1/15 (6.67%)	1/17 (5.88%)	0/18 (0.00%)
Dental caries † 1	0/15 (0.00%)	0/17 (0.00%)	3/18 (16.67%)
Diarrhoea † 1	2/15 (13.33%)	0/17 (0.00%)	1/18 (5.56%)
Dyspepsia † 1	1/15 (6.67%)	3/17 (17.65%)	3/18 (16.67%)
Dysphagia † 1	0/15 (0.00%)	1/17 (5.88%)	1/18 (5.56%)
Food poisoning † 1	1/15 (6.67%)	0/17 (0.00%)	0/18 (0.00%)
Gastritis † 1	1/15 (6.67%)	1/17 (5.88%)	1/18 (5.56%)
Gastrooesophageal reflux disease † 1	1/15 (6.67%)	0/17 (0.00%)	0/18 (0.00%)
Gingival pain † 1	1/15 (6.67%)	0/17 (0.00%)	0/18 (0.00%)
Gingival recession † 1	0/15 (0.00%)	0/17 (0.00%)	1/18 (5.56%)
Haematochezia † 1	1/15 (6.67%)	0/17 (0.00%)	0/18 (0.00%)
Intestinal haemorrhage † 1	0/15 (0.00%)	0/17 (0.00%)	1/18 (5.56%)
Lip blister † 1	1/15 (6.67%)	0/17 (0.00%)	0/18 (0.00%)
Lip ulceration † 1	1/15 (6.67%)	0/17 (0.00%)	0/18 (0.00%)
Nausea † 1	2/15 (13.33%)	0/17 (0.00%)	0/18 (0.00%)
Necrotising colitis † 1	0/15 (0.00%)	0/17 (0.00%)	1/18 (5.56%)
Noninfective gingivitis † 1	0/15 (0.00%)	0/17 (0.00%)	1/18 (5.56%)
Odynophagia † 1	0/15 (0.00%)	1/17 (5.88%)	2/18 (11.11%)
Oesophagitis † 1	0/15 (0.00%)	0/17 (0.00%)	1/18 (5.56%)
Oral pain † 1	0/15 (0.00%)	0/17 (0.00%)	1/18 (5.56%)
Proctalgia † 1	0/15 (0.00%)	0/17 (0.00%)	1/18 (5.56%)
Stomatitis † 1	0/15 (0.00%)	0/17 (0.00%)	1/18 (5.56%)
Tooth discolouration † 1	0/15 (0.00%)	1/17 (5.88%)	0/18 (0.00%)
Toothache † 1	0/15 (0.00%)	1/17 (5.88%)	7/18 (38.89%)
Vomiting † 1	2/15 (13.33%)	2/17 (11.76%)	0/18 (0.00%)
General disorders
Chest pain † 1	3/15 (20.00%)	1/17 (5.88%)	4/18 (22.22%)
Fatigue † 1	0/15 (0.00%)	0/17 (0.00%)	1/18 (5.56%)
Gait disturbance † 1	1/15 (6.67%)	0/17 (0.00%)	0/18 (0.00%)
Local swelling † 1	0/15 (0.00%)	1/17 (5.88%)	0/18 (0.00%)
Malaise † 1	1/15 (6.67%)	0/17 (0.00%)	1/18 (5.56%)
Pain † 1	0/15 (0.00%)	0/17 (0.00%)	1/18 (5.56%)
Peripheral swelling † 1	0/15 (0.00%)	1/17 (5.88%)	0/18 (0.00%)
Pyrexia † 1	3/15 (20.00%)	1/17 (5.88%)	3/18 (16.67%)
Systemic inflammatory response syndrome † 1	0/15 (0.00%)	1/17 (5.88%)	1/18 (5.56%)
Hepatobiliary disorders
Hyperbilirubinaemia † 1	0/15 (0.00%)	1/17 (5.88%)	0/18 (0.00%)
Infections and infestations
Acarodermatitis † 1	0/15 (0.00%)	0/17 (0.00%)	1/18 (5.56%)
Bronchitis † 1	0/15 (0.00%)	2/17 (11.76%)	1/18 (5.56%)
Cellulitis † 1	0/15 (0.00%)	0/17 (0.00%)	1/18 (5.56%)
Conjunctivitis † 1	0/15 (0.00%)	0/17 (0.00%)	1/18 (5.56%)
Cytomegalovirus oesophagitis † 1	0/15 (0.00%)	0/17 (0.00%)	1/18 (5.56%)
Dengue fever † 1	1/15 (6.67%)	2/17 (11.76%)	2/18 (11.11%)
Escherichia sepsis † 1	0/15 (0.00%)	0/17 (0.00%)	1/18 (5.56%)
Escherichia urinary tract infection † 1	0/15 (0.00%)	0/17 (0.00%)	2/18 (11.11%)
Flea infestation † 1	0/15 (0.00%)	0/17 (0.00%)	1/18 (5.56%)
Gastroenteritis † 1	1/15 (6.67%)	1/17 (5.88%)	1/18 (5.56%)
Gingivitis † 1	1/15 (6.67%)	4/17 (23.53%)	3/18 (16.67%)
Herpes simplex † 1	0/15 (0.00%)	0/17 (0.00%)	1/18 (5.56%)
Herpes zoster † 1	0/15 (0.00%)	0/17 (0.00%)	1/18 (5.56%)
Impetigo † 1	0/15 (0.00%)	0/17 (0.00%)	1/18 (5.56%)
Latent tuberculosis † 1	1/15 (6.67%)	0/17 (0.00%)	0/18 (0.00%)
Lice infestation † 1	0/15 (0.00%)	0/17 (0.00%)	1/18 (5.56%)
Molluscum contagiosum † 1	1/15 (6.67%)	0/17 (0.00%)	0/18 (0.00%)
Ophthalmic herpes simplex † 1	0/15 (0.00%)	1/17 (5.88%)	0/18 (0.00%)
Oral candidiasis † 1	0/15 (0.00%)	0/17 (0.00%)	3/18 (16.67%)
Oral herpes † 1	2/15 (13.33%)	1/17 (5.88%)	1/18 (5.56%)
Otitis externa † 1	0/15 (0.00%)	0/17 (0.00%)	2/18 (11.11%)
Otitis media † 1	1/15 (6.67%)	3/17 (17.65%)	2/18 (11.11%)
Otitis media chronic † 1	1/15 (6.67%)	0/17 (0.00%)	0/18 (0.00%)
Pharyngitis † 1	0/15 (0.00%)	0/17 (0.00%)	1/18 (5.56%)
Pneumocystis jirovecii pneumonia † 1	0/15 (0.00%)	1/17 (5.88%)	0/18 (0.00%)
Pneumonia † 1	0/15 (0.00%)	2/17 (11.76%)	0/18 (0.00%)
Pneumonia bacterial † 1	1/15 (6.67%)	1/17 (5.88%)	1/18 (5.56%)
Pneumonia staphylococcal † 1	0/15 (0.00%)	1/17 (5.88%)	0/18 (0.00%)
Pulmonary tuberculosis † 1	0/15 (0.00%)	0/17 (0.00%)	1/18 (5.56%)
Scarlet fever † 1	1/15 (6.67%)	0/17 (0.00%)	0/18 (0.00%)
Septic shock † 1	0/15 (0.00%)	0/17 (0.00%)	1/18 (5.56%)
Sinusitis bacterial † 1	2/15 (13.33%)	2/17 (11.76%)	3/18 (16.67%)
Subcutaneous abscess † 1	0/15 (0.00%)	1/17 (5.88%)	0/18 (0.00%)
Tinea infection † 1	0/15 (0.00%)	0/17 (0.00%)	1/18 (5.56%)
Tinea versicolour † 1	2/15 (13.33%)	2/17 (11.76%)	1/18 (5.56%)
Tonsillitis † 1	2/15 (13.33%)	0/17 (0.00%)	2/18 (11.11%)
Tooth abscess † 1	0/15 (0.00%)	1/17 (5.88%)	1/18 (5.56%)
Upper respiratory tract infection † 1	0/15 (0.00%)	1/17 (5.88%)	0/18 (0.00%)
Urinary tract infection bacterial † 1	0/15 (0.00%)	0/17 (0.00%)	1/18 (5.56%)
Viral infection † 1	0/15 (0.00%)	1/17 (5.88%)	0/18 (0.00%)
Vulvovaginitis † 1	0/15 (0.00%)	1/17 (5.88%)	1/18 (5.56%)
Injury, poisoning and procedural complications
Arthropod sting † 1	1/15 (6.67%)	0/17 (0.00%)	0/18 (0.00%)
Burns first degree † 1	0/15 (0.00%)	1/17 (5.88%)	0/18 (0.00%)
Contusion † 1	0/15 (0.00%)	0/17 (0.00%)	1/18 (5.56%)
Hand fracture † 1	0/15 (0.00%)	1/17 (5.88%)	0/18 (0.00%)
Laceration † 1	1/15 (6.67%)	0/17 (0.00%)	0/18 (0.00%)
Ligament sprain † 1	0/15 (0.00%)	1/17 (5.88%)	0/18 (0.00%)
Procedural pain † 1	0/15 (0.00%)	0/17 (0.00%)	1/18 (5.56%)
Tooth fracture † 1	0/15 (0.00%)	0/17 (0.00%)	1/18 (5.56%)
Investigations
Alanine aminotransferase † 1	0/15 (0.00%)	1/17 (5.88%)	0/18 (0.00%)
Alanine aminotransferase increased † 1	0/15 (0.00%)	2/17 (11.76%)	3/18 (16.67%)
Aspartate aminotransferase † 1	0/15 (0.00%)	1/17 (5.88%)	0/18 (0.00%)
Aspartate aminotransferase increased † 1	0/15 (0.00%)	3/17 (17.65%)	2/18 (11.11%)
Blood albumin decreased † 1	0/15 (0.00%)	0/17 (0.00%)	1/18 (5.56%)
Blood alkaline phosphatase abnormal † 1	0/15 (0.00%)	1/17 (5.88%)	0/18 (0.00%)
Blood alkaline phosphatase increased † 1	6/15 (40.00%)	2/17 (11.76%)	4/18 (22.22%)
Blood bicarbonate decreased † 1	2/15 (13.33%)	4/17 (23.53%)	4/18 (22.22%)
Blood bilirubin increased † 1	2/15 (13.33%)	4/17 (23.53%)	6/18 (33.33%)
Blood calcium decreased † 1	0/15 (0.00%)	0/17 (0.00%)	1/18 (5.56%)
Blood calcium increased † 1	3/15 (20.00%)	1/17 (5.88%)	0/18 (0.00%)
Blood cholesterol increased † 1	1/15 (6.67%)	2/17 (11.76%)	1/18 (5.56%)
Blood creatinine increased † 1	1/15 (6.67%)	2/17 (11.76%)	4/18 (22.22%)
Blood glucose decreased † 1	0/15 (0.00%)	0/17 (0.00%)	1/18 (5.56%)
Blood glucose increased † 1	1/15 (6.67%)	1/17 (5.88%)	2/18 (11.11%)
Blood pH decreased † 1	2/15 (13.33%)	1/17 (5.88%)	2/18 (11.11%)
Blood phosphorus decreased † 1	4/15 (26.67%)	3/17 (17.65%)	4/18 (22.22%)
Blood potassium decreased † 1	0/15 (0.00%)	1/17 (5.88%)	2/18 (11.11%)
Blood sodium decreased † 1	5/15 (33.33%)	2/17 (11.76%)	7/18 (38.89%)
Blood sodium increased † 1	0/15 (0.00%)	2/17 (11.76%)	2/18 (11.11%)
Blood uric acid increased † 1	0/15 (0.00%)	0/17 (0.00%)	1/18 (5.56%)
Haemoglobin decreased † 1	0/15 (0.00%)	0/17 (0.00%)	2/18 (11.11%)
Heart rate irregular † 1	1/15 (6.67%)	0/17 (0.00%)	0/18 (0.00%)
Lipase abnormal † 1	1/15 (6.67%)	1/17 (5.88%)	1/18 (5.56%)
Low density lipoprotein increased † 1	0/15 (0.00%)	1/17 (5.88%)	1/18 (5.56%)
Neutrophil count decreased † 1	2/15 (13.33%)	2/17 (11.76%)	6/18 (33.33%)
Platelet count decreased † 1	2/15 (13.33%)	2/17 (11.76%)	1/18 (5.56%)
Prothrombin time abnormal † 1	0/15 (0.00%)	0/17 (0.00%)	1/18 (5.56%)
Weight decreased † 1	0/15 (0.00%)	0/17 (0.00%)	2/18 (11.11%)
White blood cell count decreased † 1	0/15 (0.00%)	0/17 (0.00%)	2/18 (11.11%)
Metabolism and nutrition disorders
Body fat disorder † 1	0/15 (0.00%)	0/17 (0.00%)	1/18 (5.56%)
Lactic acidosis † 1	0/15 (0.00%)	1/17 (5.88%)	0/18 (0.00%)
Malnutrition † 1	0/15 (0.00%)	0/17 (0.00%)	1/18 (5.56%)
Musculoskeletal and connective tissue disorders
Arthralgia † 1	2/15 (13.33%)	4/17 (23.53%)	8/18 (44.44%)
Back pain † 1	0/15 (0.00%)	1/17 (5.88%)	2/18 (11.11%)
Bone pain † 1	0/15 (0.00%)	0/17 (0.00%)	1/18 (5.56%)
Flank pain † 1	0/15 (0.00%)	1/17 (5.88%)	0/18 (0.00%)
Kyphosis † 1	0/15 (0.00%)	1/17 (5.88%)	0/18 (0.00%)
Musculoskeletal chest pain † 1	0/15 (0.00%)	0/17 (0.00%)	1/18 (5.56%)
Myalgia † 1	6/15 (40.00%)	4/17 (23.53%)	4/18 (22.22%)
Pain in extremity † 1	0/15 (0.00%)	3/17 (17.65%)	3/18 (16.67%)
Pain in jaw † 1	0/15 (0.00%)	1/17 (5.88%)	1/18 (5.56%)
Temporomandibular joint syndrome † 1	0/15 (0.00%)	1/17 (5.88%)	1/18 (5.56%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lipoma † 1	0/15 (0.00%)	1/17 (5.88%)	0/18 (0.00%)
Penile wart † 1	0/15 (0.00%)	1/17 (5.88%)	0/18 (0.00%)
Skin papilloma † 1	1/15 (6.67%)	0/17 (0.00%)	2/18 (11.11%)
Nervous system disorders
Dizziness † 1	1/15 (6.67%)	1/17 (5.88%)	3/18 (16.67%)
Headache † 1	3/15 (20.00%)	2/17 (11.76%)	2/18 (11.11%)
Loss of consciousness † 1	0/15 (0.00%)	0/17 (0.00%)	1/18 (5.56%)
Migraine † 1	1/15 (6.67%)	0/17 (0.00%)	2/18 (11.11%)
Seizure † 1	1/15 (6.67%)	0/17 (0.00%)	1/18 (5.56%)
Tremor † 1	0/15 (0.00%)	0/17 (0.00%)	1/18 (5.56%)
Pregnancy, puerperium and perinatal conditions
Abortion early † 1	0/15 (0.00%)	1/17 (5.88%)	0/18 (0.00%)
Abortion spontaneous † 1	0/15 (0.00%)	1/17 (5.88%)	0/18 (0.00%)
Pregnancy † 1	1/15 (6.67%)	1/17 (5.88%)	0/18 (0.00%)
Psychiatric disorders
Attention deficit/hyperactivity disorder † 1	0/15 (0.00%)	1/17 (5.88%)	0/18 (0.00%)
Major depression † 1	0/15 (0.00%)	2/17 (11.76%)	1/18 (5.56%)
Substance abuse † 1	0/15 (0.00%)	0/17 (0.00%)	1/18 (5.56%)
Suicidal ideation † 1	0/15 (0.00%)	1/17 (5.88%)	0/18 (0.00%)
Renal and urinary disorders
Dysuria † 1	0/15 (0.00%)	1/17 (5.88%)	0/18 (0.00%)
Nephrolithiasis † 1	0/15 (0.00%)	1/17 (5.88%)	1/18 (5.56%)
Renal tubular dysfunction † 1	1/15 (6.67%)	0/17 (0.00%)	0/18 (0.00%)
Urethral stenosis † 1	0/15 (0.00%)	1/17 (5.88%)	0/18 (0.00%)
Reproductive system and breast disorders
Balanoposthitis † 1	0/15 (0.00%)	0/17 (0.00%)	1/18 (5.56%)
Dysmenorrhoea † 1	0/15 (0.00%)	1/17 (5.88%)	0/18 (0.00%)
Gynaecomastia † 1	1/15 (6.67%)	0/17 (0.00%)	0/18 (0.00%)
Pelvic pain † 1	1/15 (6.67%)	0/17 (0.00%)	0/18 (0.00%)
Penile pain † 1	0/15 (0.00%)	0/17 (0.00%)	1/18 (5.56%)
Polycystic ovaries † 1	0/15 (0.00%)	1/17 (5.88%)	0/18 (0.00%)
Respiratory, thoracic and mediastinal disorders
Bronchiectasis † 1	0/15 (0.00%)	0/17 (0.00%)	1/18 (5.56%)
Cough † 1	2/15 (13.33%)	2/17 (11.76%)	2/18 (11.11%)
Dyspnoea † 1	0/15 (0.00%)	1/17 (5.88%)	1/18 (5.56%)
Nasal congestion † 1	1/15 (6.67%)	1/17 (5.88%)	1/18 (5.56%)
Nasal polyps † 1	1/15 (6.67%)	0/17 (0.00%)	0/18 (0.00%)
Nasal pruritus † 1	0/15 (0.00%)	0/17 (0.00%)	1/18 (5.56%)
Pharyngeal inflammation † 1	0/15 (0.00%)	0/17 (0.00%)	1/18 (5.56%)
Pharyngeal ulceration † 1	1/15 (6.67%)	0/17 (0.00%)	0/18 (0.00%)
Pulmonary pain † 1	0/15 (0.00%)	1/17 (5.88%)	0/18 (0.00%)
Rhinorrhoea † 1	2/15 (13.33%)	0/17 (0.00%)	1/18 (5.56%)
Sinus congestion † 1	1/15 (6.67%)	0/17 (0.00%)	0/18 (0.00%)
Skin and subcutaneous tissue disorders
Acne † 1	2/15 (13.33%)	2/17 (11.76%)	1/18 (5.56%)
Alopecia † 1	0/15 (0.00%)	0/17 (0.00%)	1/18 (5.56%)
Blister † 1	1/15 (6.67%)	0/17 (0.00%)	0/18 (0.00%)
Drug eruption † 1	1/15 (6.67%)	0/17 (0.00%)	0/18 (0.00%)
Erythema † 1	0/15 (0.00%)	1/17 (5.88%)	0/18 (0.00%)
Lichen planus † 1	0/15 (0.00%)	1/17 (5.88%)	1/18 (5.56%)
Lipoatrophy † 1	0/15 (0.00%)	0/17 (0.00%)	1/18 (5.56%)
Macule † 1	0/15 (0.00%)	0/17 (0.00%)	1/18 (5.56%)
Papule † 1	1/15 (6.67%)	0/17 (0.00%)	1/18 (5.56%)
Pityriasis alba † 1	2/15 (13.33%)	0/17 (0.00%)	0/18 (0.00%)
Pruritus generalised † 1	0/15 (0.00%)	0/17 (0.00%)	1/18 (5.56%)
Vascular disorders
Hypotension † 1	0/15 (0.00%)	0/17 (0.00%)	1/18 (5.56%)
Varicose vein † 1	1/15 (6.67%)	0/17 (0.00%)	0/18 (0.00%)
1 Term from vocabulary, MedDRA 19.1; † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

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

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

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

Results Point of Contact

• Name/Title: Melissa Allen, Director, IMPAACT Operations Center
• Organization: Family Health International (FHI 360)
• Phone: (919) 405-1429
• EMail: mallen@fhi360.org

Publications:

Clay PG, Voss LE, Williams C, Daume EC. Valid treatment options for osteoporosis and osteopenia in HIV-infected persons. Ann Pharmacother. 2008 May;42(5):670-9. doi: 10.1345/aph.1K465. Epub 2008 Apr 15. Review.

McComsey GA, Kendall MA, Tebas P, Swindells S, Hogg E, Alston-Smith B, Suckow C, Gopalakrishnan G, Benson C, Wohl DA. Alendronate with calcium and vitamin D supplementation is safe and effective for the treatment of decreased bone mineral density in HIV. AIDS. 2007 Nov 30;21(18):2473-82.

Stoch SA, Saag KG, Greenwald M, Sebba AI, Cohen S, Verbruggen N, Giezek H, West J, Schnitzer TJ. Once-weekly oral alendronate 70 mg in patients with glucocorticoid-induced bone loss: a 12-month randomized, placebo-controlled clinical trial. J Rheumatol. 2009 Aug;36(8):1705-14. doi: 10.3899/jrheum.081207. Epub 2009 Jun 1.

The DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Version 1.0, December 2004 (Clarification, August 2009).

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

Jacobson DL, Lindsey JC, Gordon C, Hazra R, Spiegel H, Ferreira F, Amaral FR, Pagano-Therrien J, Gaur A, George K, Benson J, Siberry GK. Alendronate Improves Bone Mineral Density in Children and Adolescents Perinatally Infected With Human Immunodeficiency Virus With Low Bone Mineral Density for Age. Clin Infect Dis. 2020 Aug 22;71(5):1281-1288. doi: 10.1093/cid/ciz957.

• Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
• ClinicalTrials.gov Identifier: NCT00921557
• Other Study ID Numbers: P1076; 10669 ( Registry Identifier: DAIDS-ES Registry Number ); IMPAACT P1076
• First Submitted: June 12, 2009
• First Posted: June 16, 2009
• Results First Submitted: December 15, 2016
• Results First Posted: March 28, 2017
• Last Update Posted: July 21, 2017