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

• Magnitude of change in parathyroid hormone (PTH) from baseline to week 48 [ Time Frame: Baseline and Week 48 ] [ Designated as safety issue: No ]
  The magnitude of change in PTH will be measured between Baseline and Week 48. 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 [ Time Frame: Baseline, Weeks 4, 8, 12, 24, 36, and 48 ] [ Designated as safety issue: No ]
  Change from baseline to week 48 in fibroblast growth factor 23 (FGF23), 1,25 dihydroxy vitamin D (1,25-OHD), tubular reabsorption of phosphate (TRP), and glomerular filtration rate (GFR); magnitude of fold change from baseline to weeks 4, 8, 12, 24, 36, and 48; most extreme fold change from baseline to weeks 4, 8, 12, 24, 36, and 48.
  
  
• Time to most extreme fold change in PTH, FGF23, 1,25-OHD, TRP and serum creatinine (SCr) [ Time Frame: Baseline, Weeks 4, 8, 12, 24, 36, and 48 ] [ Designated as safety issue: No ]
  Time to most extreme fold change in PTH, FGF23, 1,25-OHD, TRP, and SCr.
  
  
• Change in renal-endocrine-bone biochemistry and pathophysiology (PTH, FGF23, 1,25-OHD, and TRP) [ Time Frame: Baseline, Weeks 4, 8, 12, 24, 36, and 48 ] [ Designated as safety issue: No ]
  Time to most extreme fold change; slope between baseline and the most extreme fold change for PTH, FGF23, 1,25-OHD, and TRP.
  
  
• Change in renal-endocrine-bone biochemistry and pathophysiology (PTH, FGF23, 1,25-OHD, and TRP) [ Time Frame: Baseline, Weeks 4, 8, 12, 24, 36, and 48 ] [ Designated as safety issue: No ]
  Change from baseline, magnitude of most extreme fold change, and time to most extreme fold change from baseline in PTH, FGF23, 1,25-OHD, and TRP by race and baseline vitamin D status (25-OHD serum concentration).
  
  
• Change in urine and serum calcium and phosphate (SCa, urine calcium (UCa)/urine creatinine (UCr), serum phosphate (SPO4), TRP) [ Time Frame: Baseline, Weeks 4, 8, 12, 24, 36, and 48 ] [ Designated as safety issue: No ]
  Change from baseline, magnitude of most extreme, and time to most extreme fold change from baseline in urine and serum calcium and phosphate (SCa, UCa/UCr, SPO4, TRP).
  
  
• Change in UCa/ UCr, SPO4, TRP versus changes in PTH, FGF23, 1,25-OHD [ Time Frame: Baseline, Weeks 4, 8, 12, 24, 36, and 48 ] [ Designated as safety issue: No ]
  The association between (1) the time to most extreme fold change and slope of the curve of baseline to most extreme fold change in urine and serum calcium and phosphate (SCa, UCa/UCr, SPO4, TRP) and (2) the time to most extreme fold change and slope of the curve of baseline to most extreme fold change in PTH, FGF23, 1,25-OHD.
  
  
• Change in glomerular and renal tubular function, urine retinol binding protein (URBP)/UCr, urine beta-2 microglobulin (UB2MG), urine protein (UProt)/Ucr. [ Time Frame: Baseline, Weeks 4, 8, 12, 24, 36, and 48 ] [ Designated as safety issue: No ]
  Change from baseline, magnitude of most extreme fold change, and time to most extreme fold change, and slope of the curve of baseline to most extreme fold change in glomerular function (change in SCr from baseline) and renal tubular function (urine glucose (UGluc), URBP/UCr, UB2MG, UProt/UCr).
  
  
• Change of TRP and markers of renal tubular function and endocrine change [ Time Frame: Baseline, Weeks 4, 8, 12, 24, 36, and 48 ] [ Designated as safety issue: No ]
  Association between (1) change from baseline, magnitude of most extreme fold change, time to most extreme fold change, and slope of the curve of baseline to most extreme fold change of TRP and (2) markers of renal tubular function (UGluc, URBP/UCr, UB2MG, UProt/UCr) and markers of endocrine change (PTH, FGF23).
  
  
• Change in renal-endocrine-bone biochemistry and pathophysiology [Bone alkaline phosphatase (BAP), osteocalcin (OC), C-telopeptide (CTX)] [ Time Frame: Baseline, Weeks 4, 8, 12, 24, and 48 ] [ Designated as safety issue: No ]
  Change from baseline, magnitude of most extreme fold change, time to most extreme fold change from baseline, and slope of the curve of baseline to most extreme fold change in markers of bone turnover (BAP, OC, CTX); association of these changes with endocrine controllers of calcium-phosphate balance (PTH, FGF23, 1,25-OHD), UCa/UCr, and TRP.
  
  
• Change in renal-endocrine-bone biochemistry and pathophysiology (25-OHD, 1,25-OHD) [ Time Frame: Baseline, Weeks 4, 8, 12, 24, 36, and 48 ] [ Designated as safety issue: No ]
  Association between (1) baseline values, changes from baseline, magnitude of most extreme fold change, and time to most extreme fold change from baseline, and slope of the curve of baseline to most extreme fold change for PTH, FGF23, 1,25-OHD, BAP, OC, CTX, SCr, UCa/UCr ratio, and TRP and (2) 25-OHD and 1,25-OHD serum concentrations.
  
  
• Change in bone mass density (BMD) and bone mineral content (BMC) [ Time Frame: Baseline, Weeks 4, 24, and 48 ] [ Designated as safety issue: No ]
  Association between (1) the baseline values, magnitude of most extreme fold change, and time to most extreme fold change from baseline of the markers of bone turnover (BAP, OC, CTX) and endocrine controllers of calcium-phosphate balance (PTH, FGF23, 1,25-OHD) to the baseline values and (2) the magnitude of change in BMD/BMC from baseline to weeks 24 and 48.
  
  
• Changes in markers of renal, endocrine, bone metabolism, and medication adherence [plasma or dried blood spot (DBS) emtricitabine (FTC), plasma or DBS tenofovir (TFV), red blood cell (RBC) tenofovir diphosphate (TFV-DP)] [ Time Frame: Baseline, Weeks, 4, 8, 12, 24, 36, and 48 ] [ Designated as safety issue: No ]
  Association between (1) changes in concentration of markers of renal, endocrine, and bone metabolism and (2) markers of medication adherence.
  
  
• Area under the drug concentration by time curve (AUC) for plasma or DBS FTC, plasma or DBS TFV, RBC TFV-DP; change from baseline to weeks 24 and 48 in PTH, FGF23, 1,25-OHD, BAP, OC, CTX, SCr, TRP, UCa/UCr ratio, UB2MG, UGluc, URBP/UCr ratio and BMD/BMC. [ Time Frame: Baseline, Weeks 4, 8, 12, 24, 36, and 48 ] [ Designated as safety issue: No ]
  Association of AUC (over study duration) between (1) serum FTC, serum TFV, and RBC TFV-DP and change from baseline to weeks 24 and 48 in PTH, FGF23, 1,25-OHD, BAP, OC, CTX, SCr, TRP, UCa/UCr ratio, UB2MG, UGluc, URBP/UCr ratio and BMD/BMC.
  
  
• Changes in PTH, FGF23, 1,25-OHD, BAP, OC, CTX, SCr, TRP, UCa/UCr ratio, UB2MG, UGluc, URBP/UCr ratio and BMD/BMC. [ Time Frame: Weeks 48, 72, and 96 ] [ Designated as safety issue: No ]
  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 is a prospective observational cohort sub-study of subjects enrolled in the ATN 110 or ATN 113 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 or ATN 113 study will be followed for an additional 48 weeks in the Extension Phase of ATN 110 or ATN 113 and ATN 117. 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 or ATN 113 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 and ATN 113 studies, and results will be utilized for the analysis in this study. This study does not require extra BMD or BMC measurements.