Renal, Endocrine, and Bone Changes in Response to FTC/TDF in Uninfected Young Men Who Have Sex With Men (YMSM).

Renal, Endocrine, and Bone Changes in Response to Treatment With Coformulated Emtricitabine-Tenofovir for Pre-Exposure HIV Prophylaxis (PrEP) in HIV Uninfected Young Men Who Have Sex With Men.

This is a prospective observational cohort sub-study of subjects enrolled in the Adolescent Medicine Trials Network for HIV/AIDS Interventions (ATN) 110 (NCT01772823) or ATN 113 (NCT01769456), which is a prospective interventional trial.

Study Overview

• Status: Completed
• Conditions: HIV Infection
• Intervention / Treatment: Drug: FTC/TDF (Truvada®)

Detailed Description

This is a prospective observational cohort sub-study of subjects enrolled in the ATN 110 (NCT01772823) or ATN 113 (NCT01769456) study. All subjects will be followed for at least 48 weeks. Subjects who meet specific bone or renal criteria at Week 48 of the ATN 110 (NCT01772823) or ATN 113 (NCT01769456) study will be followed for an additional 48 weeks in the Extension Phase of ATN 110 (NCT01772823) or ATN 113 (NCT01769456) and ATN 117 (NCT01769469). The maximum duration of participation will be 96 weeks.

There is no therapeutic intervention specific to this sub-study, and there are no extra study visits required for participation in this sub-study. Questionnaires will be administered and blood and urine samples for laboratory evaluation of potential emtricitabine (FTC)/tenofovir (TDF) (Truvada®) toxicities will be obtained for this sub-study at visits that are required by the ATN 110 (NCT01772823) or ATN 113 (NCT01769456) study. Measurement of bone mineral density (BMD) and bone mineral content (BMC) by dual-energy X-ray absorptiometry (DXA) scan are planned as a part of the ATN 110 (NCT01772823) and ATN 113 (NCT01769456) studies, and results will be utilized for the analysis in this study. This study does not require extra BMD or BMC measurements.

• Study Type: Observational
• Enrollment (Actual): 101

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90027
      • Children's Hopsital of Los Angeles
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Children's Hospital of Denver
  • Florida
    • Miami, Florida, United States, 33101
      • University of Miami
    • Tampa, Florida, United States, 33606
      • University Of South Florida
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Stroger Hospital and the CORE Center
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Tulane University
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins University
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Fenway Institute
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Wayne State University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Children's Hopsital of Philadelphia
  • Tennessee
    • Memphis, Tennessee, United States, 38105
      • St. Jude Childrens Research Hospital
  • Texas
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 15 years to 22 years (Child, Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

• Sampling Method: Non-Probability Sample

Study Population

Individuals between the ages 15 years 0 days to 22 years 364 days, who are enrolled in ATN 110 (NCT01772823) or ATN 113 (NCT01769456) , and agree to enter this sub-study at the same time they begin ATN 110 or ATN 113.

Description

Inclusion Criteria:

• Has been enrolled in ATN 110 (NCT01772823) or ATN 113 (NCT01769456) , and
• Willing and able to provide written informed consent

Exclusion Criteria:

-Subjects exempted from undergoing DXA scans in ATN 110 (NCT01772823) or ATN 113 (NCT01769456) are not eligible to enroll in ATN 117 (NCT01769469).

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Subjects Enrolled in ATN 110 or ATN 113; A subset of 100 participants who are enrolled in the ATN 110 or ATN 113 study will be recruited for participation in this study. There is no treatment or intervention for this study; however, all subjects will be on daily coformulated tenofovir/emtricitabine (TDF/FTC (Truvada®)) as part of the ATN 110 or ATN 113 study.	Drug: FTC/TDF (Truvada®); There are no interventions for this study except that subjects will be administered FTC/TDF (Truvada®) will be administered as part of ATN 110 and ATN 113.; Other Names: Truvada®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Magnitude of Change (Fold Change) in Parathyroid Hormone (PTH) From Baseline to Week 48	The magnitude of change in PTH will be measured between Baseline and Week 48. For any given variable, at a given time point, the magnitude of change is the fold change compared to the baseline value (if multiplied by 100 would be the percent change from baseline).	Baseline and Week (wk) 48

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Renal-endocrine-bone Biochemistry and Pathophysiology: Fibroblast Growth Factor 23 (FGF23), Change From Baseline to Week 48		Baseline and wk 48
Change in Renal-endocrine-bone Biochemistry and Pathophysiology: Fibroblast Growth Factor 23 (FGF23), Magnitude of Fold Change	The magnitude of change in FGF23 will be measured between Baseline and Week 48. For any given variable, at a given time point, the magnitude of change is the fold change compared to the baseline value (if multiplied by 100 would be the percent change from baseline).	Baseline and wk 48
Change in Renal-endocrine-bone Biochemistry and Pathophysiology: Fibroblast Growth Factor 23 (FGF23), Most Extreme Fold Change	Most extreme fold change: This is the highest or lowest value measured as fold change from the baseline value of that variable.	Baseline, Weeks 4, 8, 12, 24, 36 and 48
Change in Renal-endocrine-bone Biochemistry and Pathophysiology: Fibroblast Growth Factor 23 (FGF23), Time to Most Extreme Fold Change	The time to most extreme fold change is the study week associated with the most extreme fold change or extreme percent change from baseline.	Baseline, Weeks 4, 8, 12, 24, 36, and 48
Change in Renal-endocrine-bone Biochemistry and Pathophysiology: 1,25 Dihydroxy Vitamin D (1,25 OHD), Change From Baseline to Week 48		Baseline and wk 48
Change in Renal-endocrine-bone Biochemistry and Pathophysiology: 1,25 OHD, Magnitude of Fold Change	The magnitude of change in 1,25 OHD will be measured between Baseline and Week 48. For any given variable, at a given time point, the magnitude of change is the fold change compared to the baseline value (if multiplied by 100 would be the percent change from baseline).	Baseline and wk 48
Change in Renal-endocrine-bone Biochemistry and Pathophysiology: 1,25 OHD, Most Extreme Fold Change	Most extreme fold change: This is the highest or lowest value measured as fold change from the baseline value of that variable.	Baseline, Weeks 4, 8, 12, 24, 36 and 48
Change in Renal-endocrine-bone Biochemistry and Pathophysiology: 1,25 OHD, Time to Most Extreme Fold Change	The time to most extreme fold change is the study week associated with the most extreme fold change or extreme percent change from baseline.	Baseline, Weeks 4, 8, 12, 24, 36, and 48
Change in Renal-endocrine-bone Biochemistry and Pathophysiology: Tubular Reabsorption of Phosphate (TRP), Change From Baseline to Week 48		Baseline and wk 48
Change in Renal-endocrine-bone Biochemistry and Pathophysiology: TRP, Magnitude of Fold Change	The magnitude of change in TRP will be measured between Baseline and Week 48. For any given variable, at a given time point, the magnitude of change is the fold change compared to the baseline value (if multiplied by 100 would be the percent change from baseline).	Baseline and wk 48
Change in Renal-endocrine-bone Biochemistry and Pathophysiology: TRP, Most Extreme Fold Change	Most extreme fold change: This is the highest or lowest value measured as fold change from the baseline value of that variable.	Baseline, Weeks 4, 8, 12, 24, 36 and 48
Change in Renal-endocrine-bone Biochemistry and Pathophysiology: TRP, Time to Most Extreme Fold Change	The time to most extreme fold change is the study week associated with the most extreme fold change or extreme percent change from baseline.	Baseline, Weeks 4, 8, 12, 24, 36, and 48
Change in Renal-endocrine-bone Biochemistry and Pathophysiology: Glomerular Filtration Rate (GFR), Change From Baseline to Week 48		Baseline and wk 48
Change in Renal-endocrine-bone Biochemistry and Pathophysiology: GFR, Magnitude of Fold Change	The magnitude of change in GFR will be measured between Baseline and Week 48. For any given variable, at a given time point, the magnitude of change is the fold change compared to the baseline value (if multiplied by 100 would be the percent change from baseline).	Baseline and wk 48
Change in Renal-endocrine-bone Biochemistry and Pathophysiology: GFR, Most Extreme Fold Change	Most extreme fold change: This is the highest or lowest value measured as fold change from the baseline value of that variable.	Baseline, Weeks 4, 8, 12, 24, 36 and 48
Change in Renal-endocrine-bone Biochemistry and Pathophysiology: GFR, Time to Most Extreme Fold Change	The time to most extreme fold change is the study week associated with the most extreme fold change or extreme percent change from baseline.	Baseline, Weeks 4, 8, 12, 24, 36, and 48
Change in Renal-endocrine-bone Biochemistry and Pathophysiology: PTH, Most Extreme Fold Change	Most extreme fold change: This is the highest or lowest value measured as fold change from the baseline value of that variable.	Baseline, Weeks 4, 8, 12, 24, 36 and 48
Change in Renal-endocrine-bone Biochemistry and Pathophysiology: PTH, Time to Most Extreme Fold Change	The time to most extreme fold change is the study week associated with the most extreme fold change or extreme percent change from baseline.	Baseline, Weeks 4, 8, 12, 24, 36, and 48
Change in Renal-endocrine-bone Biochemistry and Pathophysiology: Serum Creatinine (SCr), Time to Most Extreme Fold Change	The time to most extreme fold change is the study week associated with the most extreme fold change or extreme percent change from baseline.	Baseline, Weeks 4, 8, 12, 24, 36, and 48
Change in Renal-endocrine-bone Biochemistry and Pathophysiology: PTH, Slope of the Curve of Baseline to Most Extreme Fold Change	The slope from baseline to most extreme fold change can be expressed as: Slope = [(Most extreme fold change) * (baseline value) - (baseline value)] / [(Time to most extreme fold change) - (time of the baseline value)]	Baseline, Weeks 4, 8, 12, 24, 36, and 48
Change in Renal-endocrine-bone Biochemistry and Pathophysiology: FGF23, Slope of the Curve of Baseline to Most Extreme Fold Change	The slope from baseline to most extreme fold change can be expressed as: Slope = [(Most extreme fold change) * (baseline value) - (baseline value)] / [(Time to most extreme fold change) - (time of the baseline value)]	Baseline, Weeks 4, 8, 12, 24, 36, and 48
Change in Renal-endocrine-bone Biochemistry and Pathophysiology: 1,25-OHD, Slope of the Curve of Baseline to Most Extreme Fold Change	The slope from baseline to most extreme fold change can be expressed as: Slope = [(Most extreme fold change) * (baseline value) - (baseline value)] / [(Time to most extreme fold change) - (time of the baseline value)]	Baseline, Weeks 4, 8, 12, 24, 36, and 48
Change in Renal-endocrine-bone Biochemistry and Pathophysiology: TRP, Slope of the Curve of Baseline to Most Extreme Fold Change	The slope from baseline to most extreme fold change can be expressed as: Slope = [(Most extreme fold change) * (baseline value) - (baseline value)] / [(Time to most extreme fold change) - (time of the baseline value)]	Baseline, Weeks 4, 8, 12, 24, 36, and 48
Change From Baseline to Week 48 in Serum Calcium (SCa)	Serum calcium Week 48 difference from baseline	Baseline and wk 48
Magnitude of Most Extreme Fold Change: Serum Calcium (SCa)	Most extreme fold change: This is the highest or lowest value measured as fold change from the baseline value of that variable.	Baseline, Weeks 4, 8, 12, 24, 36, and 48
Time to Most Extreme Fold Change: Serum Calcium (SCa)	The time to most extreme fold change is the study week associated with the most extreme fold change or extreme percent change from baseline.	Baseline, Weeks 4, 8, 12, 24, 36, and 48
Slope of the Curve of Baseline to Most Extreme Fold Change: Serum Calcium (SCa)	The slope from baseline to most extreme fold change can be expressed as: Slope = [(Most extreme fold change) * (baseline value) - (baseline value)] / [(Time to most extreme fold change) - (time of the baseline value)]	Baseline, Weeks 4, 8, 12, 24, 36, and 48
Change From Baseline to Week 48 in Urine Calcium (UCa) / Urine Creatinine (UCr)	Urine Calcium (UCa) / Urine Creatinine (UCr) ratio Week 48 difference from baseline	Baseline and wk 48
Magnitude of Most Extreme Fold Change: UCa/UCr Ratio	Most extreme fold change: This is the highest or lowest value measured as fold change from the baseline value of that variable.	Baseline, Weeks 4, 8, 12, 24, 36, and 48
Time to Most Extreme Fold Change: UCa/UCr Ratio	The time to most extreme fold change is the study week associated with the most extreme fold change or extreme percent change from baseline.	Baseline, Weeks 4, 8, 12, 24, 36, and 48
Slope of the Curve of Baseline to Most Extreme Fold Change: UCa/UCr Ratio	The slope from baseline to most extreme fold change can be expressed as: Slope = [(Most extreme fold change) * (baseline value) - (baseline value)] / [(Time to most extreme fold change) - (time of the baseline value)]	Baseline, Weeks 4, 8, 12, 24, 36, and 48
Change From Baseline to Week 48 in Serum Phosphate (SPO4)	Serum Phosphate (SPO4) Week 48 difference from baseline	Baseline and wk 48
Magnitude of Most Extreme Fold Change: SPO4	Most extreme fold change: This is the highest or lowest value measured as fold change from the baseline value of that variable.	Baseline, Weeks 4, 8, 12, 24, 36, and 48
Time to Most Extreme Fold Change: SPO4	The time to most extreme fold change is the study week associated with the most extreme fold change or extreme percent change from baseline.	Baseline, Weeks 4, 8, 12, 24, 36, and 48
Slope of the Curve of Baseline to Most Extreme Fold Change: SPO4	The slope from baseline to most extreme fold change can be expressed as: Slope = [(Most extreme fold change) * (baseline value) - (baseline value)] / [(Time to most extreme fold change) - (time of the baseline value)]	Baseline, Weeks 4, 8, 12, 24, 36, and 48
Change in Glomerular and Renal Tubular Function: Change From Baseline to Week 48 in Urine Retinol Binding Protein (URBP)/ Urine Creatinine (UCr)	URBP/UCr Week 48 difference from baseline	Baseline and wk 48
Change in Glomerular and Renal Tubular Function: Change From Baseline to Week 48 in Urine Beta-2 Microglobulin (UB2MG)	UB2MG Week 48 difference from baseline	Baseline and wk 48
Change in Glomerular and Renal Tubular Function: Change From Baseline to Week 48 in Urine Protein (UProt) / Urine Creatinine (UCr)	UProt/ UCr Week 48 difference from baseline	Baseline and wk 48
Change in Glomerular and Renal Tubular Function: Change From Baseline to Week 48 in Urine Glucose (UGluc)	UGluc Week 48 difference from baseline	Baseline and wk 48
Change in Glomerular and Renal Tubular Function: Change From Baseline to Week 48 in Serum Creatinine (SCr)	SCr Week 48 difference from baseline	Baseline and wk 48
Change in Glomerular and Renal Tubular Function: Magnitude of Fold Change at Week 48 in Urine Retinol Binding Protein (URBP)/ Urine Creatinine (UCr)	The magnitude of change in URBP/UCr will be measured between Baseline and Week 48. For any given variable, at a given time point, the magnitude of change is the fold change compared to the baseline value (if multiplied by 100 would be the percent change from baseline).	Baseline and wk 48
Change in Glomerular and Renal Tubular Function: Magnitude of Fold Change at Week 48 in Urine Beta-2 Microglobulin (UB2MG)	The magnitude of change in UB2MG will be measured between Baseline and Week 48. For any given variable, at a given time point, the magnitude of change is the fold change compared to the baseline value (if multiplied by 100 would be the percent change from baseline).	Baseline and wk 48
Change in Glomerular and Renal Tubular Function: Magnitude of Fold Change at Week 48 in Urine Protein (UProt)/ Urine Creatinine (UCr)	The magnitude of change in UProt/UCr will be measured between Baseline and Week 48. For any given variable, at a given time point, the magnitude of change is the fold change compared to the baseline value (if multiplied by 100 would be the percent change from baseline).	Baseline and wk 48
Change in Glomerular and Renal Tubular Function: Magnitude of Fold Change at Week 48 in Urine Glucose (UGluc)	The magnitude of change in UGluc will be measured between Baseline and Week 48. For any given variable, at a given time point, the magnitude of change is the fold change compared to the baseline value (if multiplied by 100 would be the percent change from baseline).	Baseline and wk 48
Change in Glomerular and Renal Tubular Function: Magnitude of Fold Change at Week 48 in Serum Creatinine (SCr)	The magnitude of change in SCr will be measured between Baseline and Week 48. For any given variable, at a given time point, the magnitude of change is the fold change compared to the baseline value (if multiplied by 100 would be the percent change from baseline).	Baseline and wk 48
Change in Glomerular and Renal Tubular Function: Most Extreme Fold Change in Urine Retinol Binding Protein (URBP)/ Urine Creatinine (UCr)	Most extreme fold change: This is the highest or lowest value measured as fold change from the baseline value of that variable.	Baseline, Weeks 4, 8, 12, 24, 36 and 48
Change in Glomerular and Renal Tubular Function: Most Extreme Fold Change in UB2MG	Most extreme fold change: This is the highest or lowest value measured as fold change from the baseline value of that variable.	Baseline, Weeks 4, 8, 12, 24, 36 and 48
Change in Glomerular and Renal Tubular Function: Most Extreme Fold Change in UProt/UCr	Most extreme fold change: This is the highest or lowest value measured as fold change from the baseline value of that variable.	Baseline, Weeks 4, 8, 12, 24, 36 and 48
Change in Glomerular and Renal Tubular Function: Most Extreme Fold Change in UGluc	Most extreme fold change: This is the highest or lowest value measured as fold change from the baseline value of that variable.	Baseline, Weeks 4, 8, 12, 24, 36 and 48
Change in Glomerular and Renal Tubular Function: Most Extreme Fold Change in SCr	Most extreme fold change: This is the highest or lowest value measured as fold change from the baseline value of that variable.	Baseline, Weeks 4, 8, 12, 24, 36 and 48
Change in Glomerular and Renal Tubular Function: Time to Most Extreme Fold Change in Urine Retinol Binding Protein (URBP)/ Urine Creatinine (UCr)	The time to most extreme fold change is the study week associated with the most extreme fold change or extreme percent change from baseline.	Baseline, Weeks 4, 8, 12, 24, 36, and 48
Change in Glomerular and Renal Tubular Function: Time to Most Extreme Fold Change in UB2MG	The time to most extreme fold change is the study week associated with the most extreme fold change or extreme percent change from baseline.	Baseline, Weeks 4, 8, 12, 24, 36, and 48
Change in Glomerular and Renal Tubular Function: Time to Most Extreme Fold Change in UProt/UCr	The time to most extreme fold change is the study week associated with the most extreme fold change or extreme percent change from baseline.	Baseline, Weeks 4, 8, 12, 24, 36, and 48
Change in Glomerular and Renal Tubular Function: Time to Most Extreme Fold Change in UGluc	The time to most extreme fold change is the study week associated with the most extreme fold change or extreme percent change from baseline.	Baseline, Weeks 4, 8, 12, 24, 36, and 48
Change in Glomerular and Renal Tubular Function: Slope of the Curve of Baseline to Most Extreme Fold Change in Urine Retinol Binding Protein (URBP)/ Urine Creatinine (UCr)	The slope from baseline to most extreme fold change can be expressed as: Slope = [(Most extreme fold change) * (baseline value) - (baseline value)] / [(Time to most extreme fold change) - (time of the baseline value)]	Baseline, Weeks 4, 8, 12, 24, 36, and 48
Change in Glomerular and Renal Tubular Function: Slope of the Curve of Baseline to Most Extreme Fold Change in UB2MG	The slope from baseline to most extreme fold change can be expressed as: Slope = [(Most extreme fold change) * (baseline value) - (baseline value)] / [(Time to most extreme fold change) - (time of the baseline value)]	Baseline, Weeks 4, 8, 12, 24, 36, and 48
Change in Glomerular and Renal Tubular Function: Slope of the Curve of Baseline to Most Extreme Fold Change in UProt/UCr	The slope from baseline to most extreme fold change can be expressed as: Slope = [(Most extreme fold change) * (baseline value) - (baseline value)] / [(Time to most extreme fold change) - (time of the baseline value)]	Baseline, Weeks 4, 8, 12, 24, 36, and 48
Change in Glomerular and Renal Tubular Function: Slope of the Curve of Baseline to Most Extreme Fold Change in UGluc	The slope from baseline to most extreme fold change can be expressed as: Slope = [(Most extreme fold change) * (baseline value) - (baseline value)] / [(Time to most extreme fold change) - (time of the baseline value)]	Baseline, Weeks 4, 8, 12, 24, 36, and 48
Change in Glomerular and Renal Tubular Function: Slope of the Curve of Baseline to Most Extreme Fold Change in Scr	The slope from baseline to most extreme fold change can be expressed as: Slope = [(Most extreme fold change) * (baseline value) - (baseline value)] / [(Time to most extreme fold change) - (time of the baseline value)]	Baseline, Weeks 4, 8, 12, 24, 36, and 48
Change in Renal-endocrine-bone Biochemistry and Pathophysiology: Change From Baseline to Week 48 in Osteocalcin (OC)	OC Week 48 difference from baseline	Baseline and wk 48
Change in Renal-endocrine-bone Biochemistry and Pathophysiology: Change From Baseline to Week 48 in C-Telopeptide (CTX)	CTX Week 48 difference from baseline	Baseline and wk 48
Change in Renal-endocrine-bone Biochemistry and Pathophysiology: Most Extreme Fold Change in Osteocalcin (OC)	Most extreme fold change: This is the highest or lowest value measured as fold change from the baseline value of that variable.	Baseline, Weeks 4, 8, 12, 24, 36 and 48
Change in Renal-endocrine-bone Biochemistry and Pathophysiology: Most Extreme Fold Change in C-telopeptide (CTX)	Most extreme fold change: This is the highest or lowest value measured as fold change from the baseline value of that variable.	Baseline, Weeks 4, 8, 12, 24, 36 and 48
Change in Renal-endocrine-bone Biochemistry and Pathophysiology: OC, Time to Most Extreme Fold Change	The time to most extreme fold change is the study week associated with the most extreme fold change or extreme percent change from baseline.	Baseline, Weeks 4, 8, 12, 24, 36, and 48
Change in Renal-endocrine-bone Biochemistry and Pathophysiology: Time to Most Extreme Fold Change in C-telopeptide (CTX)	The time to most extreme fold change is the study week associated with the most extreme fold change or extreme percent change from baseline.	Baseline, Weeks 4, 8, 12, 24, 36, and 48
Change in Renal-endocrine-bone Biochemistry and Pathophysiology: Slope of the Curve of Baseline to Most Extreme Fold Change in OC	The slope from baseline to most extreme fold change can be expressed as: Slope = [(Most extreme fold change) * (baseline value) - (baseline value)] / [(Time to most extreme fold change) - (time of the baseline value)]	Baseline, Weeks 4, 8, 12, 24, 36, and 48
Change in Renal-endocrine-bone Biochemistry and Pathophysiology: Slope of the Curve of Baseline to Most Extreme Fold Change in CTX	The slope from baseline to most extreme fold change can be expressed as: Slope = [(Most extreme fold change) * (baseline value) - (baseline value)] / [(Time to most extreme fold change) - (time of the baseline value)]	Baseline, Weeks (wks) 4, 8, 12, 24, 36, and 48
Area Under the Drug Concentration by Time Curve (AUC): Change From Baseline to Week 48 in PTH, by Overall Drug Exposure	Overall drug exposure categories were determined based on the overall tertiles of mean AUC dried blood spot (DBS) Red Blood Cell (RBC) Tenofovir Diphosphate (intracellular) (TFV-DP). Comparisons were performed between the high exposure group and the low exposure group. The time points at which data were collected were: weeks 4, 8, 12, 24, 36, and 48.	Baseline and wk 48
Area Under the Drug Concentration by Time Curve (AUC): Change From Baseline to Week 24 in PTH, by Overall Drug Exposure	Overall drug exposure categories were determined based on the overall tertiles of mean AUC dried blood spot (DBS) Red Blood Cell (RBC) Tenofovir Diphosphate (intracellular) (TFV-DP). Comparisons were performed between the high exposure group and the low exposure group. The time points at which data were collected were: weeks 4, 8, 12, and 24.	Baseline and wk 24
Area Under the Drug Concentration by Time Curve (AUC): Change From Baseline to Week 24 in FGF23, by Overall Drug Exposure	Overall drug exposure categories were determined based on the overall tertiles of mean AUC dried blood spot (DBS) Red Blood Cell (RBC) Tenofovir Diphosphate (intracellular) (TFV-DP). Comparisons were performed between the high exposure group and the low exposure group. The time points at which data were collected were: weeks 4, 8, 12, and 24.	Baseline and wk 24
Area Under the Drug Concentration by Time Curve (AUC): Change From Baseline to Week 48 in FGF23, by Overall Drug Exposure	Overall drug exposure categories were determined based on the overall tertiles of mean AUC dried blood spot (DBS) Red Blood Cell (RBC) Tenofovir Diphosphate (intracellular) (TFV-DP). Comparisons were performed between the high exposure group and the low exposure group. The time points at which data were collected were: weeks 4, 8, 12, 24, 36, and 48.	Baseline and wk 48
Area Under the Drug Concentration by Time Curve (AUC): Change From Baseline to Week 24 in 1,25 OHD, by Overall Drug Exposure	Overall drug exposure categories were determined based on the overall tertiles of mean AUC dried blood spot (DBS) Red Blood Cell (RBC) Tenofovir Diphosphate (intracellular) (TFV-DP). Comparisons were performed between the high exposure group and the low exposure group. The time points at which data were collected were: weeks 4, 8, 12, and 24.	Baseline and wk 24
Area Under the Drug Concentration by Time Curve (AUC): Change From Baseline to Week 48 in 1,25 OHD, by Overall Drug Exposure	Overall drug exposure categories were determined based on the overall tertiles of mean AUC dried blood spot (DBS) Red Blood Cell (RBC) Tenofovir Diphosphate (intracellular) (TFV-DP). Comparisons were performed between the high exposure group and the low exposure group. The time points at which data were collected were: weeks 4, 8, 12, 24, 36, and 48.	Baseline and wk 48
Area Under the Drug Concentration by Time Curve (AUC): Change From Baseline to Week 24 in Osteocalcin (OC), by Overall Drug Exposure	Overall drug exposure categories were determined based on the overall tertiles of mean AUC dried blood spot (DBS) Red Blood Cell (RBC) Tenofovir Diphosphate (intracellular) (TFV-DP). Comparisons were performed between the high exposure group and the low exposure group. The time points at which data were collected were: weeks 4, 8, 12, and 24.	Baseline and wk 24
Area Under the Drug Concentration by Time Curve (AUC): Change From Baseline to Week 48 in Osteocalcin (OC), by Overall Drug Exposure	Overall drug exposure categories were determined based on the overall tertiles of mean AUC dried blood spot (DBS) Red Blood Cell (RBC) Tenofovir Diphosphate (intracellular) (TFV-DP). Comparisons were performed between the high exposure group and the low exposure group. The time points at which data were collected were: weeks 4, 8, 12, 24, 36, and 48.	Baseline and wk 48
Area Under the Drug Concentration by Time Curve (AUC): Change From Baseline to Week 24 in CTX, by Overall Drug Exposure	Overall drug exposure categories were determined based on the overall tertiles of mean AUC dried blood spot (DBS) Red Blood Cell (RBC) Tenofovir Diphosphate (intracellular) (TFV-DP). Comparisons were performed between the high exposure group and the low exposure group. The time points at which data were collected were: weeks 4, 8, 12, and 24.	Baseline and wk 24
Area Under the Drug Concentration by Time Curve (AUC): Change From Baseline to Week 48 in CTX, by Overall Drug Exposure	Overall drug exposure categories were determined based on the overall tertiles of mean AUC dried blood spot (DBS) Red Blood Cell (RBC) Tenofovir Diphosphate (intracellular) (TFV-DP). Comparisons were performed between the high exposure group and the low exposure group. The time points at which data were collected were: weeks 4, 8, 12, 24, 36, and 48.	Baseline and wk 48
Area Under the Drug Concentration by Time Curve (AUC): Change From Baseline to Week 24 in SCr, by Overall Drug Exposure	Overall drug exposure categories were determined based on the overall tertiles of mean AUC dried blood spot (DBS) Red Blood Cell (RBC) Tenofovir Diphosphate (intracellular) (TFV-DP). Comparisons were performed between the high exposure group and the low exposure group. The time points at which data were collected were: weeks 4, 8, 12, and 24.	Baseline and wk 24
Area Under the Drug Concentration by Time Curve (AUC): Change From Baseline to Week 48 in SCr, by Overall Drug Exposure	Overall drug exposure categories were determined based on the overall tertiles of mean AUC dried blood spot (DBS) Red Blood Cell (RBC) Tenofovir Diphosphate (intracellular) (TFV-DP). Comparisons were performed between the high exposure group and the low exposure group. The time points at which data were collected were: weeks 4, 8, 12, 24, 36, and 48.	Baseline and wk 48
Area Under the Drug Concentration by Time Curve (AUC): Change From Baseline to Week 24 in TRP, by Overall Drug Exposure	Overall drug exposure categories were determined based on the overall tertiles of mean AUC dried blood spot (DBS) Red Blood Cell (RBC) Tenofovir Diphosphate (intracellular) (TFV-DP). Comparisons were performed between the high exposure group and the low exposure group. The time points at which data were collected were: weeks 4, 8, 12, and 24.	Baseline and wk 24
Area Under the Drug Concentration by Time Curve (AUC): Change From Baseline to Week 48 in TRP, by Overall Drug Exposure	Overall drug exposure categories were determined based on the overall tertiles of mean AUC dried blood spot (DBS) Red Blood Cell (RBC) Tenofovir Diphosphate (intracellular) (TFV-DP). Comparisons were performed between the high exposure group and the low exposure group. The time points at which data were collected were: weeks 4, 8, 12, 24, 36, and 48.	Baseline and wk 48
Area Under the Drug Concentration by Time Curve (AUC): Change From Baseline to Week 24 in UCa/UCr Ratio, by Overall Drug Exposure	Overall drug exposure categories were determined based on the overall tertiles of mean AUC dried blood spot (DBS) Red Blood Cell (RBC) Tenofovir Diphosphate (intracellular) (TFV-DP). Comparisons were performed between the high exposure group and the low exposure group. The time points at which data were collected were: weeks 4, 8, 12, and 24.	Baseline and wk 24
Area Under the Drug Concentration by Time Curve (AUC): Change From Baseline to Week 48 in UCa/UCr Ratio, by Overall Drug Exposure	Overall drug exposure categories were determined based on the overall tertiles of mean AUC dried blood spot (DBS) Red Blood Cell (RBC) Tenofovir Diphosphate (intracellular) (TFV-DP). Comparisons were performed between the high exposure group and the low exposure group. The time points at which data were collected were: weeks 4, 8, 12, 24, 36, and 48.	Baseline and wk 48
Area Under the Drug Concentration by Time Curve (AUC): Change From Baseline to Week 24 in UB2MG, by Overall Drug Exposure	Overall drug exposure categories were determined based on the overall tertiles of mean AUC dried blood spot (DBS) Red Blood Cell (RBC) Tenofovir Diphosphate (intracellular) (TFV-DP). Comparisons were performed between the high exposure group and the low exposure group. The time points at which data were collected were: weeks 4, 8, 12, and 24.	Baseline and wk 24
Area Under the Drug Concentration by Time Curve (AUC): Change From Baseline to Week 48 in UB2MG, by Overall Drug Exposure	Overall drug exposure categories were determined based on the overall tertiles of mean AUC dried blood spot (DBS) Red Blood Cell (RBC) Tenofovir Diphosphate (intracellular) (TFV-DP). Comparisons were performed between the high exposure group and the low exposure group. The time points at which data were collected were: weeks 4, 8, 12, 24, 36, and 48.	Baseline and wk 48
Area Under the Drug Concentration by Time Curve (AUC): Change From Baseline to Week 24 in UGluc, by Overall Drug Exposure	Overall drug exposure categories were determined based on the overall tertiles of mean AUC dried blood spot (DBS) Red Blood Cell (RBC) Tenofovir Diphosphate (intracellular) (TFV-DP). Comparisons were performed between the high exposure group and the low exposure group. The time points at which data were collected were: weeks 4, 8, 12, and 24.	Baseline and wk 24
Area Under the Drug Concentration by Time Curve (AUC): Change From Baseline to Week 48 in UGluc, by Overall Drug Exposure	Overall drug exposure categories were determined based on the overall tertiles of mean AUC dried blood spot (DBS) Red Blood Cell (RBC) Tenofovir Diphosphate (intracellular) (TFV-DP). Comparisons were performed between the high exposure group and the low exposure group. The time points at which data were collected were: weeks 4, 8, 12, 24, 36, and 48.	Baseline and wk 48
Area Under the Drug Concentration by Time Curve (AUC): Change From Baseline to Week 24 in URBP/UCr Ratio, by Overall Drug Exposure	Overall drug exposure categories were determined based on the overall tertiles of mean AUC dried blood spot (DBS) Red Blood Cell (RBC) Tenofovir Diphosphate (intracellular) (TFV-DP). Comparisons were performed between the high exposure group and the low exposure group. The time points at which data were collected were: weeks 4, 8, 12, and 24.	Baseline and wk 24
Area Under the Drug Concentration by Time Curve (AUC): Change From Baseline to Week 48 in URBP/UCr Ratio, by Overall Drug Exposure	Overall drug exposure categories were determined based on the overall tertiles of mean AUC dried blood spot (DBS) Red Blood Cell (RBC) Tenofovir Diphosphate (intracellular) (TFV-DP). Comparisons were performed between the high exposure group and the low exposure group. The time points at which data were collected were: weeks 4, 8, 12, 24, 36, and 48.	Baseline and wk 48
Area Under the Drug Concentration by Time Curve (AUC): Percent Change From Baseline to Week 24 in Lumbar Spine BMD, by Overall Drug Exposure	Overall drug exposure categories were determined based on the overall tertiles of mean AUC dried blood spot (DBS) Red Blood Cell (RBC) Tenofovir Diphosphate (intracellular) (TFV-DP). Comparisons were performed between the high exposure group and the low exposure group. The time points at which data were collected were: weeks 4, 8, 12, and 24.	Baseline and wk 24
Area Under the Drug Concentration by Time Curve (AUC): Percent Change From Baseline to Week 48 in Lumbar Spine BMD, by Overall Drug Exposure	Overall drug exposure categories were determined based on the overall tertiles of mean AUC dried blood spot (DBS) Red Blood Cell (RBC) Tenofovir Diphosphate (intracellular) (TFV-DP). Comparisons were performed between the high exposure group and the low exposure group. The time points at which data were collected were: weeks 4, 8, 12, 24, 36, and 48.	Baseline and wk 48
Area Under the Drug Concentration by Time Curve (AUC): Change From Baseline to Week 24 in Lumbar Spine BMD Z-score, by Overall Drug Exposure	Overall drug exposure categories were determined based on the overall tertiles of mean AUC dried blood spot (DBS) Red Blood Cell (RBC) Tenofovir Diphosphate (intracellular) (TFV-DP). Comparisons were performed between the high exposure group and the low exposure group. The Z-score is the standard deviation around mean bone mineral density, adjusted for sex, age, and race/ethnicity. An average Z-score of zero would be expected in this group of healthy adolescents and young adults. An increase in Z-score would signify acceleration of accrual of bone mass, a positive outcome; a decrease in Z-score would signify either bone loss or failure to accrue the expected amount of bone mass, both of which are adverse outcomes. The Z-score is a normalized measure. The time points at which data were collected were: weeks 4, 8, 12, and 24.	Baseline and wk 24
Area Under the Drug Concentration by Time Curve (AUC): Change From Baseline to Week 48 in Lumbar Spine BMD Z-score, by Overall Drug Exposure	Overall drug exposure categories were determined based on the overall tertiles of mean AUC dried blood spot (DBS) Red Blood Cell (RBC) Tenofovir Diphosphate (intracellular) (TFV-DP). Comparisons were performed between the high exposure group and the low exposure group. The Z-score is the standard deviation around mean bone mineral density, adjusted for sex, age, and race/ethnicity. An average Z-score of zero would be expected in this group of healthy adolescents and young adults. An increase in Z-score would signify acceleration of accrual of bone mass, a positive outcome; a decrease in Z-score would signify either bone loss or failure to accrue the expected amount of bone mass, both of which are adverse outcomes. The Z-score is a normalized measure. The time points at which data were collected were: weeks 4, 8, 12, 24, 36, and 48.	Baseline and wk 48
Area Under the Drug Concentration by Time Curve (AUC): Percent Change From Baseline to Week 24 in Femoral Neck BMD, by Overall Drug Exposure	Overall drug exposure categories were determined based on the overall tertiles of mean AUC dried blood spot (DBS) Red Blood Cell (RBC) Tenofovir Diphosphate (intracellular) (TFV-DP). Comparisons were performed between the high exposure group and the low exposure group. The time points at which data were collected were: weeks 4, 8, 12, and 24.	Baseline and wk 24
Area Under the Drug Concentration by Time Curve (AUC): Percent Change From Baseline to Week 48 in Femoral Neck BMD, by Overall Drug Exposure	Overall drug exposure categories were determined based on the overall tertiles of mean AUC dried blood spot (DBS) Red Blood Cell (RBC) Tenofovir Diphosphate (intracellular) (TFV-DP). Comparisons were performed between the high exposure group and the low exposure group. The time points at which data were collected were: weeks 4, 8, 12, 24, 36, and 48.	Baseline and wk 48
Area Under the Drug Concentration by Time Curve (AUC): Change From Baseline to Week 24 in Femoral Neck BMD Z-score, by Overall Drug Exposure	Overall drug exposure categories were determined based on the overall tertiles of mean AUC dried blood spot (DBS) Red Blood Cell (RBC) Tenofovir Diphosphate (intracellular) (TFV-DP). Comparisons were performed between the high exposure group and the low exposure group. The Z-score is the standard deviation around mean bone mineral density, adjusted for sex, age, and race/ethnicity. An average Z-score of zero would be expected in this group of healthy adolescents and young adults. An increase in Z-score would signify acceleration of accrual of bone mass, a positive outcome; a decrease in Z-score would signify either bone loss or failure to accrue the expected amount of bone mass, both of which are adverse outcomes. The Z-score is a normalized measure. The time points at which data were collected were: weeks 4, 8, 12, and 24.	Baseline and wk 24
Area Under the Drug Concentration by Time Curve (AUC): Change From Baseline to Week 48 in Femoral Neck BMD Z-score, by Overall Drug Exposure	Overall drug exposure categories were determined based on the overall tertiles of mean AUC dried blood spot (DBS) Red Blood Cell (RBC) Tenofovir Diphosphate (intracellular) (TFV-DP). Comparisons were performed between the high exposure group and the low exposure group. The Z-score is the standard deviation around mean bone mineral density, adjusted for sex, age, and race/ethnicity. An average Z-score of zero would be expected in this group of healthy adolescents and young adults. An increase in Z-score would signify acceleration of accrual of bone mass, a positive outcome; a decrease in Z-score would signify either bone loss or failure to accrue the expected amount of bone mass, both of which are adverse outcomes. The Z-score is a normalized measure. The time points at which data were collected were: weeks 4, 8, 12, 24, 36, and 48.	Baseline and wk 48
Area Under the Drug Concentration by Time Curve (AUC): Percent Change From Baseline to Week 24 in Total Body BMC, by Overall Drug Exposure	Overall drug exposure categories were determined based on the overall tertiles of mean AUC dried blood spot (DBS) Red Blood Cell (RBC) Tenofovir Diphosphate (intracellular) (TFV-DP). Comparisons were performed between the high exposure group and the low exposure group. The time points at which data were collected were: weeks 4, 8, 12, and 24.	Baseline and wk 24
Area Under the Drug Concentration by Time Curve (AUC): Percent Change From Baseline to Week 48 in Total Body BMC, by Overall Drug Exposure	Overall drug exposure categories were determined based on the overall tertiles of mean AUC dried blood spot (DBS) Red Blood Cell (RBC) Tenofovir Diphosphate (intracellular) (TFV-DP). Comparisons were performed between the high exposure group and the low exposure group. The time points at which data were collected were: weeks 4, 8, 12, 24, 36, and 48.	Baseline and wk 48
Magnitude of Change in Lumbar Spine BMD at Week 48	The magnitude of change will be measured between Baseline and Week 48. For any given variable, at a given time point, the magnitude of change is the fold change compared to the baseline value (if multiplied by 100 would be the percent change from baseline).	Baseline and wk 48
Magnitude of Change in Lumbar Spine BMD Z-score at Week 48	The magnitude of change will be measured between Baseline and Week 48. For any given variable, at a given time point, the magnitude of change is the fold change compared to the baseline value (if multiplied by 100 would be the percent change from baseline). The Z-score is the standard deviation around mean bone mineral density, adjusted for sex, age, and race/ethnicity. An average Z-score of zero would be expected in this group of healthy adolescents and young adults. An increase in Z-score would signify acceleration of accrual of bone mass, a positive outcome; a decrease in Z-score would signify either bone loss or failure to accrue the expected amount of bone mass, both of which are adverse outcomes. The Z-score is a normalized measure.	Baseline and wk 48
Magnitude of Change in Femoral Neck BMD at Week 48	The magnitude of change will be measured between Baseline and Week 48. For any given variable, at a given time point, the magnitude of change is the fold change compared to the baseline value (if multiplied by 100 would be the percent change from baseline).	Baseline and wk 48
Magnitude of Change in Femoral Neck BMD Z-score at Week 48	The magnitude of change will be measured between Baseline and Week 48. For any given variable, at a given time point, the magnitude of change is the fold change compared to the baseline value (if multiplied by 100 would be the percent change from baseline).	Baseline and wk 48
Magnitude of Change in Total Body BMC at Week 48	The magnitude of change will be measured between Baseline and Week 48. For any given variable, at a given time point, the magnitude of change is the fold change compared to the baseline value (if multiplied by 100 would be the percent change from baseline).	Baseline and wk 48
Changes in BMD/BMC in the Extension Phase: Lumbar Spine BMD Change at EPH1 From Baseline	For subjects in the extension phase of the study, the last measured values at the ATN 110 or ATN 113 study week 48 visit will be compared with those measured at the Extension Phase visit 1 (EPH 1, 24 weeks after the ATN 110 or ATN 113 study week 48 visit) and EPH 2 (48 weeks after the ATN 110 or ATN 113 study week 48 visit). This measure shows the difference between the Baseline measure and the first Extension Phase visit (BL - EPH1)	Baseline and wk 72
Changes in BMD/BMC in the Extension Phase: Lumbar Spine BMD Change at EPH2 From Baseline	For subjects in the extension phase of the study, the last measured values at the ATN 110 or ATN 113 study week 48 visit will be compared with those measured at the Extension Phase visit 1 (EPH 1, 24 weeks after the ATN 110 or ATN 113 study week 48 visit) and EPH 2 (48 weeks after the ATN 110 or ATN 113 study week 48 visit). This measure shows the difference between the Baseline measure and the second Extension Phase visit (BL - EPH2)	Baseline and wk 96
Changes in BMD/BMC in the Extension Phase: Lumbar Spine BMD Change at EPH1 From Week 48 (or Last Visit on Study)	For subjects in the extension phase of the study, the last measured values at the ATN 110 or ATN 113 study week 48 visit will be compared with those measured at the Extension Phase visit 1 (EPH 1, 24 weeks after the ATN 110 or ATN 113 study week 48 visit) and EPH 2 (48 weeks after the ATN 110 or ATN 113 study week 48 visit). This measure shows the difference between the last measure on study and the first Extension Phase visit (Last - EPH1)	Wk 48 (or last available measurement on study), Wk 72
Changes in BMD/BMC in the Extension Phase: Lumbar Spine BMD Change at EPH2 From Week 48 (or Last Visit on Study)	For subjects in the extension phase of the study, the last measured values at the ATN 110 or ATN 113 study week 48 visit will be compared with those measured at the Extension Phase visit 1 (EPH 1, 24 weeks after the ATN 110 or ATN 113 study week 48 visit) and EPH 2 (48 weeks after the ATN 110 or ATN 113 study week 48 visit). This measure shows the difference between the last measure on study and the second Extension Phase visit (Last - EPH2)	Wk 48 (or last available measurement on study), Wk 96
Changes in BMD/BMC in the Extension Phase: Lumbar Spine BMD Z-score Change at EPH1 From Baseline	For subjects in the extension phase of the study, the last measured values at the ATN 110 or ATN 113 study week 48 visit will be compared with those measured at the Extension Phase visit 1 (EPH 1, 24 weeks after the ATN 110 or ATN 113 study week 48 visit) and EPH 2 (48 weeks after the ATN 110 or ATN 113 study week 48 visit). This measure shows the difference between the Baseline measure and the first Extension Phase visit (BL - EPH1). The Z-score is the standard deviation around mean bone mineral density, adjusted for sex, age, and race/ethnicity. An average Z-score of zero would be expected in this group of healthy adolescents and young adults. An increase in Z-score would signify acceleration of accrual of bone mass, a positive outcome; a decrease in Z-score would signify either bone loss or failure to accrue the expected amount of bone mass, both of which are adverse outcomes. The Z-score is a normalized measure.	Baseline and wk 72
Changes in BMD/BMC in the Extension Phase: Lumbar Spine BMD Z-score Change at EPH2 From Baseline	For subjects in the extension phase of the study, the last measured values at the ATN 110 or ATN 113 study week 48 visit will be compared with those measured at the Extension Phase visit 1 (EPH 1, 24 weeks after the ATN 110 or ATN 113 study week 48 visit) and EPH 2 (48 weeks after the ATN 110 or ATN 113 study week 48 visit). This measure shows the difference between the Baseline measure and the second Extension Phase visit (BL - EPH2) The Z-score is the standard deviation around mean bone mineral density, adjusted for sex, age, and race/ethnicity. An average Z-score of zero would be expected in this group of healthy adolescents and young adults. An increase in Z-score would signify acceleration of accrual of bone mass, a positive outcome; a decrease in Z-score would signify either bone loss or failure to accrue the expected amount of bone mass, both of which are adverse outcomes. The Z-score is a normalized measure.	Baseline and wk 96
Changes in BMD/BMC in the Extension Phase: Lumbar Spine BMD Z-score Change at EPH1 From Week 48 (or Last Visit on Study)	For subjects in the extension phase of the study, the last measured values at the ATN 110 or ATN 113 study week 48 visit will be compared with those measured at the Extension Phase visit 1 (EPH 1, 24 weeks after the ATN 110 or ATN 113 study week 48 visit) and EPH 2 (48 weeks after the ATN 110 or ATN 113 study week 48 visit). This measure shows the difference between the last measure on study and the first Extension Phase visit (Last - EPH1) The Z-score is the standard deviation around mean bone mineral density, adjusted for sex, age, and race/ethnicity. An average Z-score of zero would be expected in this group of healthy adolescents and young adults. An increase in Z-score would signify acceleration of accrual of bone mass, a positive outcome; a decrease in Z-score would signify either bone loss or failure to accrue the expected amount of bone mass, both of which are adverse outcomes. The Z-score is a normalized measure.	Wk 48 (or last available measurement on study), Wk 72
Changes in BMD/BMC in the Extension Phase: Lumbar Spine BMD Z-score Change at EPH2 From Week 48 (or Last Visit on Study)	For subjects in the extension phase of the study, the last measured values at the ATN 110 or ATN 113 study week 48 visit will be compared with those measured at the Extension Phase visit 1 (EPH 1, 24 weeks after the ATN 110 or ATN 113 study week 48 visit) and EPH 2 (48 weeks after the ATN 110 or ATN 113 study week 48 visit). This measure shows the difference between the last measure on study and the second Extension Phase visit (Last - EPH2) The Z-score is the standard deviation around mean bone mineral density, adjusted for sex, age, and race/ethnicity. An average Z-score of zero would be expected in this group of healthy adolescents and young adults. An increase in Z-score would signify acceleration of accrual of bone mass, a positive outcome; a decrease in Z-score would signify either bone loss or failure to accrue the expected amount of bone mass, both of which are adverse outcomes. The Z-score is a normalized measure.	Wk 48 (or last available measurement on study), Wk 96
Changes in BMD/BMC in the Extension Phase: Femoral Neck BMD Change at EPH1 From Baseline	For subjects in the extension phase of the study, the last measured values at the ATN 110 or ATN 113 study week 48 visit will be compared with those measured at the Extension Phase visit 1 (EPH 1, 24 weeks after the ATN 110 or ATN 113 study week 48 visit) and EPH 2 (48 weeks after the ATN 110 or ATN 113 study week 48 visit). This measure shows the difference between the Baseline measure and the first Extension Phase visit (BL - EPH1)	Baseline and wk 72
Changes in BMD/BMC in the Extension Phase: Femoral Neck BMD Change at EPH2 From Baseline	For subjects in the extension phase of the study, the last measured values at the ATN 110 or ATN 113 study week 48 visit will be compared with those measured at the Extension Phase visit 1 (EPH 1, 24 weeks after the ATN 110 or ATN 113 study week 48 visit) and EPH 2 (48 weeks after the ATN 110 or ATN 113 study week 48 visit). This measure shows the difference between the Baseline measure and the second Extension Phase visit (BL - EPH2)	Baseline and wk 96
Changes in BMD/BMC in the Extension Phase: Femoral Neck BMD Change at EPH1 From Week 48 (or Last Visit on Study)	For subjects in the extension phase of the study, the last measured values at the ATN 110 or ATN 113 study week 48 visit will be compared with those measured at the Extension Phase visit 1 (EPH 1, 24 weeks after the ATN 110 or ATN 113 study week 48 visit) and EPH 2 (48 weeks after the ATN 110 or ATN 113 study week 48 visit). This measure shows the difference between the last measure on study and the first Extension Phase visit (Last- EPH1)	Wk 48 (or last available measurement on study), Wk 72
Changes in BMD/BMC in the Extension Phase: Femoral Neck BMD Change at EPH2 From Week 48 (or Last Visit on Study)	For subjects in the extension phase of the study, the last measured values at the ATN 110 or ATN 113 study week 48 visit will be compared with those measured at the Extension Phase visit 1 (EPH 1, 24 weeks after the ATN 110 or ATN 113 study week 48 visit) and EPH 2 (48 weeks after the ATN 110 or ATN 113 study week 48 visit). This measure shows the difference between the last measure on study and the second Extension Phase visit (Last- EPH2)	W 48 (or last available measurement on study), Wk 96
Changes in BMD/BMC in the Extension Phase: Femoral Neck BMD Z-score Change at EPH1 From Baseline	For subjects in the extension phase of the study, the last measured values at the ATN 110 or ATN 113 study week 48 visit will be compared with those measured at the Extension Phase visit 1 (EPH 1, 24 weeks after the ATN 110 or ATN 113 study week 48 visit) and EPH 2 (48 weeks after the ATN 110 or ATN 113 study week 48 visit). This measure shows the difference between the Baseline measure and the first Extension Phase visit (BL - EPH1) The Z-score is the standard deviation around mean bone mineral density, adjusted for sex, age, and race/ethnicity. An average Z-score of zero would be expected in this group of healthy adolescents and young adults. An increase in Z-score would signify acceleration of accrual of bone mass, a positive outcome; a decrease in Z-score would signify either bone loss or failure to accrue the expected amount of bone mass, both of which are adverse outcomes. The Z-score is a normalized measure.	Baseline and wk 72
Changes in BMD/BMC in the Extension Phase: Femoral Neck BMD Z-score Change at EPH2 From Baseline	For subjects in the extension phase of the study, the last measured values at the ATN 110 or ATN 113 study week 48 visit will be compared with those measured at the Extension Phase visit 1 (EPH 1, 24 weeks after the ATN 110 or ATN 113 study week 48 visit) and EPH 2 (48 weeks after the ATN 110 or ATN 113 study week 48 visit). This measure shows the difference between the Baseline measure and the second Extension Phase visit (BL - EPH2) The Z-score is the standard deviation around mean bone mineral density, adjusted for sex, age, and race/ethnicity. An average Z-score of zero would be expected in this group of healthy adolescents and young adults. An increase in Z-score would signify acceleration of accrual of bone mass, a positive outcome; a decrease in Z-score would signify either bone loss or failure to accrue the expected amount of bone mass, both of which are adverse outcomes. The Z-score is a normalized measure.	Baseline, Week 96
Changes in BMD/BMC in the Extension Phase: Femoral Neck BMD Z-score Change at EPH1 From Week 48 (or Last Visit on Study)	For subjects in the extension phase of the study, the last measured values at the ATN 110 or ATN 113 study week 48 visit will be compared with those measured at the Extension Phase visit 1 (EPH 1, 24 weeks after the ATN 110 or ATN 113 study week 48 visit) and EPH 2 (48 weeks after the ATN 110 or ATN 113 study week 48 visit). This measure shows the difference between the last measure on study and the first Extension Phase visit (Last - EPH1) The Z-score is the standard deviation around mean bone mineral density, adjusted for sex, age, and race/ethnicity. An average Z-score of zero would be expected in this group of healthy adolescents and young adults. An increase in Z-score would signify acceleration of accrual of bone mass, a positive outcome; a decrease in Z-score would signify either bone loss or failure to accrue the expected amount of bone mass, both of which are adverse outcomes. The Z-score is a normalized measure.	Week 48 (or last available measurement on study), Week 72
Changes in BMD/BMC in the Extension Phase: Femoral Neck BMD Z-score Change at EPH2 From Week 48 (or Last Visit on Study)	For subjects in the extension phase of the study, the last measured values at the ATN 110 or ATN 113 study week 48 visit will be compared with those measured at the Extension Phase visit 1 (EPH 1, 24 weeks after the ATN 110 or ATN 113 study week 48 visit) and EPH 2 (48 weeks after the ATN 110 or ATN 113 study week 48 visit). This measure shows the difference between the last measure on study and the second Extension Phase visit (Last - EPH2). The Z-score is the standard deviation around mean bone mineral density, adjusted for sex, age, and race/ethnicity. An average Z-score of zero would be expected in this group of healthy adolescents and young adults. An increase in Z-score would signify acceleration of accrual of bone mass, a positive outcome; a decrease in Z-score would signify either bone loss or failure to accrue the expected amount of bone mass, both of which are adverse outcomes. The Z-score is a normalized measure.	Wk 48 (or last available measurement on study), Wk 96
Changes in BMD/BMC in the Extension Phase: Total Body BMC Change at EPH1 From Baseline	For subjects in the extension phase of the study, the last measured values at the ATN 110 or ATN 113 study week 48 visit will be compared with those measured at the Extension Phase visit 1 (EPH 1, 24 weeks after the ATN 110 or ATN 113 study week 48 visit) and EPH 2 (48 weeks after the ATN 110 or ATN 113 study week 48 visit). This measure shows the difference between the Baseline measure and the first Extension Phase visit (BL - EPH1)	Baseline and wk 72
Changes in BMD/BMC in the Extension Phase: Total Body BMC Change at EPH2 From Baseline	For subjects in the extension phase of the study, the last measured values at the ATN 110 or ATN 113 study week 48 visit will be compared with those measured at the Extension Phase visit 1 (EPH 1, 24 weeks after the ATN 110 or ATN 113 study week 48 visit) and EPH 2 (48 weeks after the ATN 110 or ATN 113 study week 48 visit). This measure shows the difference between the Baseline measure and the second Extension Phase visit (BL - EPH2)	Baseline and wk 96
Changes in BMD/BMC in the Extension Phase: Total Body BMC Change at EPH1 From Week 48 (or Last Visit on Study)	For subjects in the extension phase of the study, the last measured values at the ATN 110 or ATN 113 study week 48 visit will be compared with those measured at the Extension Phase visit 1 (EPH 1, 24 weeks after the ATN 110 or ATN 113 study week 48 visit) and EPH 2 (48 weeks after the ATN 110 or ATN 113 study week 48 visit). This measure shows the difference between the last measure on study and the first Extension Phase visit (Last- EPH1)	Wk 48 (or last available measurement on study), Wk 72
Changes in BMD/BMC in the Extension Phase: Total Body BMC Change at EPH2 From Week 48 (or Last Visit on Study)	For subjects in the extension phase of the study, the last measured values at the ATN 110 or ATN 113 study week 48 visit will be compared with those measured at the Extension Phase visit 1 (EPH 1, 24 weeks after the ATN 110 or ATN 113 study week 48 visit) and EPH 2 (48 weeks after the ATN 110 or ATN 113 study week 48 visit). This measure shows the difference between the last measure on study and the second Extension Phase visit (Last- EPH2)	Wk 48 (or last available measurement on study), Wk 96

Collaborators and Investigators

• Sponsor: University of North Carolina, Chapel Hill
• Collaborators: National Institute on Drug Abuse (NIDA); Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); National Institute of Mental Health (NIMH)
• Investigators: Study Chair: Peter Havens, MD, MACC Fund Research Center

Publications and helpful links

General Publications

• Havens PL, Long D, Schuster GU, Gordon CM, Price G, Wilson CM, Kapogiannis BG, Mulligan K, Stephensen CB; Adolescent Medicine Trials Network for HIV/AIDS Interventions (ATN) 117 and 109 study teams. Tenofovir disoproxil fumarate appears to disrupt the relationship of vitamin D and parathyroid hormone. Antivir Ther. 2018;23(7):623-628. doi: 10.3851/IMP3269. Epub 2018 Sep 27.
• Havens PL, Stephensen CB, Van Loan MD, Schuster GU, Woodhouse LR, Flynn PM, Gordon CM, Pan CG, Rutledge B, Liu N, Wilson CM, Hazra R, Hosek SG, Anderson PL, Seifert SM, Kapogiannis BG, Mulligan K; Adolescent Medicine Trials Network for HIV/AIDS Interventions 117 study team. Decline in Bone Mass With Tenofovir Disoproxil Fumarate/Emtricitabine Is Associated With Hormonal Changes in the Absence of Renal Impairment When Used by HIV-Uninfected Adolescent Boys and Young Men for HIV Preexposure Prophylaxis. Clin Infect Dis. 2017 Feb 1;64(3):317-325. doi: 10.1093/cid/ciw765. Epub 2016 Nov 15.
• Havens PL, Tamhane A, Stephensen CB, Schuster GU, Gordon CM, Liu N, Wilson CM, Hosek SG, Anderson PL, Kapogiannis BG, Mulligan K. Short Communication: Association of Vitamin D Insufficiency and Protective Tenofovir Diphosphate Concentrations with Bone Toxicity in Adolescent Boys and Young Men Using Tenofovir Disoproxil Fumarate/Emtricitabine for HIV Pre-Exposure Prophylaxis. AIDS Res Hum Retroviruses. 2019 Feb;35(2):123-128. doi: 10.1089/AID.2018.0096. Epub 2018 Nov 5.

Helpful Links

• ATN Website

Study record dates

Study Major Dates

• Study Start: November 1, 2012
• Primary Completion (Actual): November 1, 2015
• Study Completion (Actual): November 1, 2015

Study Registration Dates

• First Submitted: January 14, 2013
• First Submitted That Met QC Criteria: January 14, 2013
• First Posted (Estimate): January 16, 2013

Study Record Updates

• Last Update Posted (Actual): March 27, 2019
• Last Update Submitted That Met QC Criteria: March 25, 2019
• Last Verified: November 1, 2018

More Information

Terms related to this study

• Keywords: PrEP; HIV prevention; Truvada; Tenofovir; Emtricitabine; Renal, endocrine, bone changes
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; HIV Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination
• Other Study ID Numbers: ATN 117 Version 2.0