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

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.

Lek: 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.

Inne nazwy:

• Truvada®

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).

Change in Renal-endocrine-bone Biochemistry and Pathophysiology: Fibroblast Growth Factor 23 (FGF23), Change From Baseline to Week 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).

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.

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.

Change in Renal-endocrine-bone Biochemistry and Pathophysiology: 1,25 Dihydroxy Vitamin D (1,25 OHD), Change From Baseline to Week 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).

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.

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.

Change in Renal-endocrine-bone Biochemistry and Pathophysiology: Tubular Reabsorption of Phosphate (TRP), Change From Baseline to Week 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).

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.

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.

Change in Renal-endocrine-bone Biochemistry and Pathophysiology: Glomerular Filtration Rate (GFR), Change From Baseline to Week 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).

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.

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.

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.

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.

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.

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)]

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)]

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)]

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)]

Change From Baseline to Week 48 in Serum Calcium (SCa)

Serum calcium Week 48 difference from baseline

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.

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.

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)]

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

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.

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.

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)]

Change From Baseline to Week 48 in Serum Phosphate (SPO4)

Serum Phosphate (SPO4) Week 48 difference from baseline

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.

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.

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)]

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

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

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

Change in Glomerular and Renal Tubular Function: Change From Baseline to Week 48 in Urine Glucose (UGluc)

UGluc Week 48 difference from baseline

Change in Glomerular and Renal Tubular Function: Change From Baseline to Week 48 in Serum Creatinine (SCr)

SCr Week 48 difference from baseline

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).

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).

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).

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).

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).

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.

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.

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.

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.

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.

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.

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.

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.

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.

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)]

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)]

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)]

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)]

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)]

Change in Renal-endocrine-bone Biochemistry and Pathophysiology: Change From Baseline to Week 48 in Osteocalcin (OC)

OC Week 48 difference from baseline

Change in Renal-endocrine-bone Biochemistry and Pathophysiology: Change From Baseline to Week 48 in C-Telopeptide (CTX)

CTX Week 48 difference from baseline

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.

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.

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.

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.

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)]

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)]

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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).

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.

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).

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).

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).

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)

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)

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)

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)

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.

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.

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.

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.

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)

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)

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)

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)

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.

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.

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.

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.

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)

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)

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)

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)