Trial Outcomes & Findings for Safety and Effectiveness of Alendronate for Bone Mineral Density in HIV-infected Children and Adolescents (NCT NCT00921557)

Last Updated: 2021-11-05

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

52 participants

Primary outcome timeframe

Weeks 0, 24 and 48

Results posted on

2021-11-05

Participant Flow

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.

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.

Participant milestones

Participant milestones
Measure	1A: Alendronate/Alendronate Participants received alendronate for 96 weeks	1B: Alendronate/Placebo Participants received alendronate for 48 weeks followed by placebo for 48 weeks	2: Placebo/Alendronate Participants received placebo for 48 weeks followed by alendronate for 48 weeks
Weeks 0-48 (on Study Treatment) STARTED	17	17	18
Weeks 0-48 (on Study Treatment) COMPLETED	15	17	18
Weeks 0-48 (on Study Treatment) NOT COMPLETED	2	0	0
Weeks 48-96 (on Study Treatment) STARTED	15	17	18
Weeks 48-96 (on Study Treatment) COMPLETED	15	16	17
Weeks 48-96 (on Study Treatment) NOT COMPLETED	0	1	1
Weeks 96-144 (Off Study Treatment) STARTED	15	16	17
Weeks 96-144 (Off Study Treatment) COMPLETED	12	15	16
Weeks 96-144 (Off Study Treatment) NOT COMPLETED	3	1	1

Reasons for withdrawal

Reasons for withdrawal
Measure	1A: Alendronate/Alendronate Participants received alendronate for 96 weeks	1B: Alendronate/Placebo Participants received alendronate for 48 weeks followed by placebo for 48 weeks	2: Placebo/Alendronate Participants received placebo for 48 weeks followed by alendronate for 48 weeks
Weeks 0-48 (on Study Treatment) Baseline lumbar spine > -1.5	2	0	0
Weeks 48-96 (on Study Treatment) Site Closure	0	1	0
Weeks 48-96 (on Study Treatment) Became a ward of the state	0	0	1
Weeks 96-144 (Off Study Treatment) Site closure	1	0	0
Weeks 96-144 (Off Study Treatment) Not able to attend clinic	2	1	1

Baseline Characteristics

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.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	1A: Alendronate/Alendronate n=15 Participants Participants received alendronate for 96 weeks	1B: Alendronate/Placebo n=17 Participants Participants received alendronate for 48 weeks followed by placebo for 48 weeks	2: Placebo/Alendronate n=18 Participants Participants received placebo for 48 weeks followed by alendronate for 48 weeks	Total n=50 Participants Total of all reporting groups
Age, Continuous	16 years n=15 Participants	16 years n=17 Participants	16 years n=18 Participants	16 years n=50 Participants
Age, Customized 11 - < 15 years	7 Participants n=15 Participants	4 Participants n=17 Participants	6 Participants n=18 Participants	17 Participants n=50 Participants
Age, Customized 15 - < 19 years	6 Participants n=15 Participants	9 Participants n=17 Participants	8 Participants n=18 Participants	23 Participants n=50 Participants
Age, Customized >= 19 years	2 Participants n=15 Participants	4 Participants n=17 Participants	4 Participants n=18 Participants	10 Participants n=50 Participants
Sex: Female, Male Female	5 Participants n=15 Participants	6 Participants n=17 Participants	5 Participants n=18 Participants	16 Participants n=50 Participants
Sex: Female, Male Male	10 Participants n=15 Participants	11 Participants n=17 Participants	13 Participants n=18 Participants	34 Participants n=50 Participants
Race/Ethnicity, Customized White non-Hispanic	3 Participants n=15 Participants	3 Participants n=17 Participants	1 Participants n=18 Participants	7 Participants n=50 Participants
Race/Ethnicity, Customized Black non-Hispanic	2 Participants n=15 Participants	4 Participants n=17 Participants	1 Participants n=18 Participants	7 Participants n=50 Participants
Race/Ethnicity, Customized Hispanic (regardless of race)	10 Participants n=15 Participants	10 Participants n=17 Participants	16 Participants n=18 Participants	36 Participants n=50 Participants
Region of Enrollment United States	6 Participants n=15 Participants	8 Participants n=17 Participants	7 Participants n=18 Participants	21 Participants n=50 Participants
Region of Enrollment Brazil	9 Participants n=15 Participants	9 Participants n=17 Participants	11 Participants n=18 Participants	29 Participants n=50 Participants
Tanner stage 1	1 Participants n=15 Participants	0 Participants n=17 Participants	2 Participants n=18 Participants	3 Participants n=50 Participants
Tanner stage 2	3 Participants n=15 Participants	2 Participants n=17 Participants	2 Participants n=18 Participants	7 Participants n=50 Participants
Tanner stage 3	5 Participants n=15 Participants	1 Participants n=17 Participants	2 Participants n=18 Participants	8 Participants n=50 Participants
Tanner stage 4	1 Participants n=15 Participants	8 Participants n=17 Participants	6 Participants n=18 Participants	15 Participants n=50 Participants
Tanner stage 5	5 Participants n=15 Participants	6 Participants n=17 Participants	6 Participants n=18 Participants	17 Participants n=50 Participants
Smoker Yes	0 Participants n=15 Participants	2 Participants n=17 Participants	1 Participants n=18 Participants	3 Participants n=50 Participants
Smoker No	15 Participants n=15 Participants	15 Participants n=17 Participants	17 Participants n=18 Participants	47 Participants n=50 Participants
Bone age	14 years n=15 Participants • 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.	16 years n=16 Participants • 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.	15 years n=18 Participants • 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.	15 years n=49 Participants • 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 Yes	7 Participants n=15 Participants	7 Participants n=17 Participants	9 Participants n=18 Participants	23 Participants n=50 Participants
Use of tenofovir No	8 Participants n=15 Participants	10 Participants n=17 Participants	9 Participants n=18 Participants	27 Participants n=50 Participants
CDC HIV disease category A/1	0 Participants n=15 Participants	1 Participants n=17 Participants	3 Participants n=18 Participants	4 Participants n=50 Participants
CDC HIV disease category B/2	2 Participants n=15 Participants	0 Participants n=17 Participants	6 Participants n=18 Participants	8 Participants n=50 Participants
CDC HIV disease category C/3	13 Participants n=15 Participants	16 Participants n=17 Participants	9 Participants n=18 Participants	38 Participants n=50 Participants
HIV-1 RNA (copies/ml) <= 400	10 Participants n=15 Participants	16 Participants n=17 Participants	15 Participants n=18 Participants	41 Participants n=50 Participants
HIV-1 RNA (copies/ml) >400	5 Participants n=15 Participants	1 Participants n=17 Participants	3 Participants n=18 Participants	9 Participants n=50 Participants
CD4 cell count (cells/mm^3) 200 - <500	3 Participants n=15 Participants	3 Participants n=17 Participants	2 Participants n=18 Participants	8 Participants n=50 Participants
CD4 cell count (cells/mm^3) 500 - < 1000	10 Participants n=15 Participants	10 Participants n=17 Participants	10 Participants n=18 Participants	30 Participants n=50 Participants
CD4 cell count (cells/mm^3) >= 1000	2 Participants n=15 Participants	4 Participants n=17 Participants	6 Participants n=18 Participants	12 Participants n=50 Participants
25-OH Vitamin D (ng/mL) 10 - < 20	1 Participants n=15 Participants	5 Participants n=17 Participants	0 Participants n=18 Participants	6 Participants n=50 Participants
25-OH Vitamin D (ng/mL) 20 - < 30	7 Participants n=15 Participants	8 Participants n=17 Participants	6 Participants n=18 Participants	21 Participants n=50 Participants
25-OH Vitamin D (ng/mL) >= 30	7 Participants n=15 Participants	4 Participants n=17 Participants	12 Participants n=18 Participants	23 Participants n=50 Participants
Lumbar spine BMD (g/cm^2)	0.64 g/cm^2 n=15 Participants	0.73 g/cm^2 n=17 Participants	0.66 g/cm^2 n=18 Participants	0.70 g/cm^2 n=50 Participants
Whole body (with head) BMD (g/cm^2)	0.87 g/cm^2 n=14 Participants • Whole body (with head) BMD was missing at entry for some participants because of software problems with the DXA machines.	0.91 g/cm^2 n=16 Participants • Whole body (with head) BMD was missing at entry for some participants because of software problems with the DXA machines.	0.86 g/cm^2 n=16 Participants • Whole body (with head) BMD was missing at entry for some participants because of software problems with the DXA machines.	0.87 g/cm^2 n=46 Participants • Whole body (with head) BMD was missing at entry for some participants because of software problems with the DXA machines.

PRIMARY outcome

Timeframe: Weeks 0, 24 and 48

Population: Includes all participants who started study treatment

Outcome measures

Outcome measures
Measure	1: Alendronate n=32 Participants Participants received alendronate for 48 weeks	2: Placebo n=18 Participants Participants received placebo for 48 weeks	2: Placebo/Alendronate Participants received placebo for 48 weeks followed by alendronate for 48 weeks
Percent Change From Baseline to Weeks 24 and 48 in Lumbar Spine BMD Week 24	14.4 Percent change from baseline Interval 8.8 to 19.4	5.5 Percent change from baseline Interval 1.2 to 7.6	—
Percent Change From Baseline to Weeks 24 and 48 in Lumbar Spine BMD Week 48	15.9 Percent change from baseline Interval 9.2 to 25.3	7.1 Percent change from baseline Interval 4.9 to 8.9	—

PRIMARY outcome

Timeframe: Week 0 to 48

Population: All participants who started study treatment

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.

Outcome measures

Outcome measures
Measure	1: Alendronate n=32 Participants Participants received alendronate for 48 weeks	2: Placebo n=18 Participants Participants received placebo for 48 weeks	2: Placebo/Alendronate Participants received placebo for 48 weeks followed by alendronate for 48 weeks
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	5 Participants	2 Participants	—

SECONDARY outcome

Timeframe: Weeks 0, 24 and 48

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

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.

Outcome measures

Outcome measures
Measure	1: Alendronate n=30 Participants Participants received alendronate for 48 weeks	2: Placebo n=16 Participants Participants received placebo for 48 weeks	2: Placebo/Alendronate Participants received placebo for 48 weeks followed by alendronate for 48 weeks
Percent Change From Baseline to Weeks 24 and 48 in Whole Body (With Head) BMD Week 24	5.5 Percent change from baseline Interval 3.7 to 8.1	0.3 Percent change from baseline Interval -0.5 to 3.6	—
Percent Change From Baseline to Weeks 24 and 48 in Whole Body (With Head) BMD Week 48	10.7 Percent change from baseline Interval 6.0 to 16.2	5.2 Percent change from baseline Interval 1.6 to 8.5	—

SECONDARY outcome

Timeframe: Weeks 0 and 96

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

Percent change was calculated as (measurement at week 96 - measurement at baseline)/measurement at baseline \* 100%. Includes Groups 1A and 1B only.

Outcome measures

Outcome measures
Measure	1: Alendronate n=14 Participants Participants received alendronate for 48 weeks	2: Placebo n=16 Participants Participants received placebo for 48 weeks	2: Placebo/Alendronate Participants received placebo for 48 weeks followed by alendronate for 48 weeks
Percent Change From Baseline to Week 96 in Lumbar Spine BMD	24.9 Percent change from baseline Interval 11.1 to 69.8	14.8 Percent change from baseline Interval 11.4 to 32.6	—

SECONDARY outcome

Timeframe: Weeks 0 and 96

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

Percent change was calculated as (measurement at week 96 - measurement at baseline)/measurement at baseline \* 100%. Includes Groups 1A and 1B only.

Outcome measures

Outcome measures
Measure	1: Alendronate n=12 Participants Participants received alendronate for 48 weeks	2: Placebo n=14 Participants Participants received placebo for 48 weeks	2: Placebo/Alendronate Participants received placebo for 48 weeks followed by alendronate for 48 weeks
Percent Change From Baseline to Week 96 in Whole Body (With Head) BMD	19.6 Percent change from baseline Interval 7.7 to 30.4	10.3 Percent change from baseline Interval 5.1 to 24.9	—

SECONDARY outcome

Timeframe: Weeks 0 to 144

Population: All participants who started treatment

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).

Outcome measures

Outcome measures
Measure	1: Alendronate n=15 Participants Participants received alendronate for 48 weeks	2: Placebo n=17 Participants Participants received placebo for 48 weeks	2: Placebo/Alendronate n=18 Participants Participants received placebo for 48 weeks followed by alendronate for 48 weeks
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 Week 48 to 96	1 Participants	3 Participants	2 Participants
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 Week 0 to 48	2 Participants	3 Participants	2 Participants
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 Week 96 to 144	3 Participants	4 Participants	3 Participants

SECONDARY outcome

Timeframe: Weeks 0, 24 and 48

Population: Participants who started study treatment

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.

Outcome measures

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

SECONDARY outcome

Timeframe: Weeks 0, 24 and 48

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

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.

Outcome measures

Outcome measures
Measure	1: Alendronate n=30 Participants Participants received alendronate for 48 weeks	2: Placebo n=16 Participants Participants received placebo for 48 weeks	2: Placebo/Alendronate Participants received placebo for 48 weeks followed by alendronate for 48 weeks
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. On tenofovir	13.2 percentage of baseline Interval 7.6 to 18.8	5.0 percentage of baseline Interval 1.5 to 8.6	—
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. Not on tenofovir	11.6 percentage of baseline Interval 6.7 to 16.5	5.8 percentage of baseline Interval 0.5 to 11.2	—
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. 25-0H Vit D<30 ng/ml	10.6 percentage of baseline Interval 5.6 to 15.6	5.8 percentage of baseline Interval -2.7 to 14.3	—
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. 25-0H Vit D>=30 ng/ml	15.1 percentage of baseline Interval 10.6 to 19.5	5.2 percentage of baseline Interval 2.3 to 8.0	—
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. Bone age < 15 years	19.0 percentage of baseline Interval 14.7 to 23.3	8.4 percentage of baseline Interval 4.7 to 12.1	—
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. Bone age >=15 years	7.7 percentage of baseline Interval 4.1 to 11.2	2.3 percentage of baseline Interval -0.6 to 5.2	—
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. Tanner stage <= 3	18.0 percentage of baseline Interval 10.5 to 25.5	8.0 percentage of baseline Interval 2.9 to 13.2	—
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. Tanner stage >= 4	9.4 percentage of baseline Interval 5.9 to 12.8	3.8 percentage of baseline Interval 0.6 to 7.0	—
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. Male	11.4 percentage of baseline Interval 7.4 to 15.3	4.1 percentage of baseline Interval 1.1 to 7.1	—
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. Female	14.0 percentage of baseline Interval 6.0 to 22.0	8.2 percentage of baseline Interval 1.6 to 14.7	—
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. Non-Hispanic	9.8 percentage of baseline Interval 2.7 to 17.0	0.3 percentage of baseline Interval -4.4 to 4.9	—
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. Hispanic	13.9 percentage of baseline Interval 10.0 to 17.7	6.1 percentage of baseline Interval 3.3 to 8.9	—
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. 11 - < 15 years	19.2 percentage of baseline Interval 12.9 to 25.5	8.0 percentage of baseline Interval 2.9 to 13.2	—
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. 15 - < 19 years	10.5 percentage of baseline Interval 6.1 to 14.9	6.5 percentage of baseline Interval 3.0 to 10.0	—
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. >= 19 years	4.7 percentage of baseline Interval -2.0 to 11.4	-0.3 percentage of baseline Interval -3.8 to 3.2	—

SECONDARY outcome

Timeframe: Weeks 48, 96 and 144

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

Percent change was calculated as (measurement at time T2 - measurement at time T1)/measurement at Time T1 \* 100%.

Outcome measures

Outcome measures
Measure	1: Alendronate n=15 Participants Participants received alendronate for 48 weeks	2: Placebo n=15 Participants Participants received placebo for 48 weeks	2: Placebo/Alendronate n=15 Participants Participants received placebo for 48 weeks followed by alendronate for 48 weeks
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	0.9 Percent change Interval -1.1 to 6.4	2.0 Percent change Interval -0.6 to 4.6	1.7 Percent change Interval -1.0 to 6.1

SECONDARY outcome

Timeframe: Weeks 48, 96 and 144

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

Percent change was calculated as (measurement at time T2 - measurement at time T2)/measurement at time T1 \* 100%.

Outcome measures

Outcome measures
Measure	1: Alendronate n=15 Participants Participants received alendronate for 48 weeks	2: Placebo n=13 Participants Participants received placebo for 48 weeks	2: Placebo/Alendronate n=15 Participants Participants received placebo for 48 weeks followed by alendronate for 48 weeks
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	0.8 Percent change Interval -1.9 to 3.1	0.5 Percent change Interval -0.4 to 2.1	0.9 Percent change Interval 0.0 to 5.9

SECONDARY outcome

Timeframe: Weeks 0, 48, 96 and 144

Population: Participants who started study treatment.

Percent calculated as number of participants with HIV-1 RNA \<= 400 copies/ml relative to the number of participants with HIV-1 RNA measured at that time point.

Outcome measures

Outcome measures
Measure	1: Alendronate n=15 Participants Participants received alendronate for 48 weeks	2: Placebo n=17 Participants Participants received placebo for 48 weeks	2: Placebo/Alendronate n=18 Participants Participants received placebo for 48 weeks followed by alendronate for 48 weeks
Percent of Participants With HIV-1 RNA <= 400 Copies/ml Week 0	10 Participants	16 Participants	15 Participants
Percent of Participants With HIV-1 RNA <= 400 Copies/ml Week 48	10 Participants	16 Participants	14 Participants
Percent of Participants With HIV-1 RNA <= 400 Copies/ml Week 96	12 Participants	12 Participants	13 Participants
Percent of Participants With HIV-1 RNA <= 400 Copies/ml Week 144	10 Participants	10 Participants	10 Participants

SECONDARY outcome

Timeframe: Weeks 0, 48, 96 and 144

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

Change in percentage of lymphocytes that are CD4 cells calculated as measurement at each time point minus baseline measurement

Outcome measures

Outcome measures
Measure	1: Alendronate n=15 Participants Participants received alendronate for 48 weeks	2: Placebo n=17 Participants Participants received placebo for 48 weeks	2: Placebo/Alendronate n=18 Participants Participants received placebo for 48 weeks followed by alendronate for 48 weeks
Change in CD4 Percent From Baseline Week 48 - Week 0	0 percent of lymphocytes that are CD4 cell Interval -3.0 to 4.0	1 percent of lymphocytes that are CD4 cell Interval -2.0 to 3.0	1 percent of lymphocytes that are CD4 cell Interval -2.0 to 4.0
Change in CD4 Percent From Baseline Week 96 - Week 0	0 percent of lymphocytes that are CD4 cell Interval -5.0 to 4.0	-1 percent of lymphocytes that are CD4 cell Interval -3.0 to 3.0	2 percent of lymphocytes that are CD4 cell Interval -4.0 to 3.0
Change in CD4 Percent From Baseline Week 144 - Week 0	1 percent of lymphocytes that are CD4 cell Interval -9.0 to 4.0	-1 percent of lymphocytes that are CD4 cell Interval -3.0 to 4.0	-4 percent of lymphocytes that are CD4 cell Interval -5.0 to 8.0

SECONDARY outcome

Timeframe: Weeks 144

Population: Participants who started study treatment.

Percentage of participants advancing in CDC HIV disease category from baseline throughout study follow-up

Outcome measures

Outcome measures
Measure	1: Alendronate n=15 Participants Participants received alendronate for 48 weeks	2: Placebo n=17 Participants Participants received placebo for 48 weeks	2: Placebo/Alendronate n=18 Participants Participants received placebo for 48 weeks followed by alendronate for 48 weeks
Change in Centers for Disease Control (CDC) HIV Disease Category Week 0 to 48	1 Participants	0 Participants	0 Participants
Change in Centers for Disease Control (CDC) HIV Disease Category Week 48 to 96	0 Participants	1 Participants	0 Participants
Change in Centers for Disease Control (CDC) HIV Disease Category Week 96 to 144	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Weeks 48, 96 and 144

Outcome measure required additional funding for laboratory testing which was not available, so this outcome is not reported.

Outcome measures

Outcome data not reported

Adverse Events

1A: Alendronate/Alendronate

Serious events: 2 serious events

Other events: 15 other events

Deaths: 0 deaths

1B: Alendronate/Placebo

Serious events: 2 serious events

Other events: 17 other events

Deaths: 0 deaths

2: Placebo/Alendronate

Serious events: 3 serious events

Other events: 18 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	1A: Alendronate/Alendronate n=15 participants at risk Participants received alendronate for 48 weeks	1B: Alendronate/Placebo n=17 participants at risk Participants received alendronate for 48 weeks followed by placebo for 48 weeks	2: Placebo/Alendronate n=18 participants at risk Participants received placebo for 48 weeks followed by alendronate for 48 weeks
Blood and lymphatic system disorders Neutropenia	0.00% 0/15 • From first dose of study treatment to end of follow-up (144 weeks) 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.	0.00% 0/17 • From first dose of study treatment to end of follow-up (144 weeks) 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.	5.6% 1/18 • From first dose of study treatment to end of follow-up (144 weeks) 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.
Infections and infestations Pneumonia	0.00% 0/15 • From first dose of study treatment to end of follow-up (144 weeks) 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.	5.9% 1/17 • From first dose of study treatment to end of follow-up (144 weeks) 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.	0.00% 0/18 • From first dose of study treatment to end of follow-up (144 weeks) 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.
Infections and infestations Pneumonia bacterial	0.00% 0/15 • From first dose of study treatment to end of follow-up (144 weeks) 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.	5.9% 1/17 • From first dose of study treatment to end of follow-up (144 weeks) 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.	0.00% 0/18 • From first dose of study treatment to end of follow-up (144 weeks) 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.
Infections and infestations Tuberculosis	0.00% 0/15 • From first dose of study treatment to end of follow-up (144 weeks) 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.	0.00% 0/17 • From first dose of study treatment to end of follow-up (144 weeks) 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.	5.6% 1/18 • From first dose of study treatment to end of follow-up (144 weeks) 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.
Musculoskeletal and connective tissue disorders Arthritis	6.7% 1/15 • From first dose of study treatment to end of follow-up (144 weeks) 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.	0.00% 0/17 • From first dose of study treatment to end of follow-up (144 weeks) 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.	0.00% 0/18 • From first dose of study treatment to end of follow-up (144 weeks) 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Burkitt's lymphoma	0.00% 0/15 • From first dose of study treatment to end of follow-up (144 weeks) 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.	0.00% 0/17 • From first dose of study treatment to end of follow-up (144 weeks) 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.	5.6% 1/18 • From first dose of study treatment to end of follow-up (144 weeks) 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.
Nervous system disorders Epilepsy	6.7% 1/15 • From first dose of study treatment to end of follow-up (144 weeks) 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.	0.00% 0/17 • From first dose of study treatment to end of follow-up (144 weeks) 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.	0.00% 0/18 • From first dose of study treatment to end of follow-up (144 weeks) 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.

Other adverse events

Additional Information

Melissa Allen, Director, IMPAACT Operations Center

Family Health International (FHI 360)

Phone: (919) 405-1429

Email: [email protected]

Results disclosure agreements

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

Restriction type: OTHER