1. AfterBefore PTH pg/ml 200 150 100 50 0 PTH pg/ml AfterBefore 200 150 100 50 0 Case Report 1) Age 53, 17 yrs HIV infection TDF/FTC/EFZ Baseline 25(OH)D 10.3ng/ml, PTH 159 pg/ml 5 months VitaminD3/ Calcium citrate Repeat 25(OH)D 24.5ng/ml, PTH 85 pg/ml Case Report 2) Age 55, 20 yrs HIV infection TDF/FTC/EFZ Baseline 25(OH)D 15.1ng/ml, PTH 139 pg/ml 3 months VitaminD3/ Calcium citrate Repeat 25(OH)D 35.4 ng/ml, PTH 78 pg/ml Abnormalities of bone and calcium are common in HIV patients. 1 Tenofovir (TDF) decreases bone density in children and adults and causes skeletal lesions in fetal primates. 2,3 Vitamin D insufficiency is common in the population 4 Low vitamin D [measured by 25(OH)D] is a known cause of secondary hyperparathyroidism Secondary hyperparathyroidism indicates abnormal calcium metabolism and causes osteopenia and osteoporosis. In subjects with normal renal function, high PTH is alsoassociated with LV hypertrophy, incident hypertension, higher risk of metabolic syndrome and poorer performance on cognitive tests 5,6 We aimed to assess vitamin D status and to determine its influence on the relationship between anti-retroviral medications and abnormal calcium/bone metabolism. We hypothesized that the effect of TDF on bone is mediated via effects on the 25(OH)D-calcium-PTH axis Should Vitamin D Be Prescribed with Tenofovir/FTC? K. CHILDS, S. FISHMAN, K. BATEMAN, S. FACTOR, C. WYATT, M. MULLEN, A. BRANCH; Mount Sinai School of Medicine, New York, NY. BACKGROUND References 1)Brown and Qaqish AIDS 2006 2) Purdy et al J.Pediatr 2008 3) Gallant et al JAMA 2004 4) Holick MF. N Engl J Med 2007 5)Saleh et al. Eur Heart J 2003 6) Forman et al Hypertension 2008. Acknowledgements The work was supported, in part, by NIH grants DA016156 and DK066939 (to ADB) Age a 49 (43, 55) Years HIV12 (7, 19) % Caucasian80% % on TDF/FTC66% Serum creatinine (0.5-1.3 mg/dl) 0.9 (0.8, 1.1) Corrected calcium (8.6-10.2 mg/dl) 9.3 (9.1, 9.5) CD4 count (500-1500 cells/mm3) 443 (290, 698) % HIV viral load undetectable 75% Thirty-nine percent of subjects exposed to the combination of TDF/FTC and suboptimal 25(OH)D had elevated PTH Patients on TDF/FTC should have 25(OH)D and PTH levels checked Low 25(OH)D and TDF/FTC appear to act synergistically to increase PTH level We hypothesize that TDF/FTC causes a reduction in whole body calcium, which results in elevated PTH (model) Research is needed to investigate whether prophylactic use of vitamin D3 supplements and calcium citrate will prevent increases in PTH and preserve bone. 25(OH)D insufficiency was common Among subjects on ART who had low vitamin D: PTH was above the ULN in 39% of those on tenofovir/emtricitabine (TDF/FTC) versus 7% on TDF-sparing regimens (p= 0.036) Median plasma PTH was 80 pg/ml on TDF/FTC versus 55 pg/ml on ART without TDF/FTC (p=0.02). No subject with optimal 25(OH)D levels had elevated PTH Multivariable analysis showed that 25(OH)D levels (p=0.03) and TDF/FTC use (p=0.04) were independently associated with plasma PTH, serum creatinine was not. TDF/FTC IS ASSOCIATED WITH ELEVATED PTH Contact: kathryn.childs@mssm.edu or andrea.branch@mssm.edu kathryn.childs@mssm.edu Anecdotal case reports: FUTURE RESEARCH DIRECTIONS CONCLUSIONSRESULTS TDF/FTC was associated with higher plasma PTH in subjects with suboptimal 25(OH)D Fig 1) PTH and 25(OH)D levels among subjects taking ART not including TDF/FTC Fig 2a) PTH and 25(OH)D levels among subjects taking TDF/FTC Fig 2b) Among subjects taking TDF/FTC, plasma PTH was significantly higher in subjects with suboptimal 25(OH)D than with optimal 25(OH)D Fig 3a) PTH and 25(OH)D levels among all subjects on ART Fig 3b) Among subjects with suboptimal 25(OH)D, plasma PTH was significantly higher in subjects taking TDF/FTC than those on other ART. Low Serum Phosphate Increased PTH Decreased Bone Mineral Density Decreased Whole-body Calcium Increased Resorbption of Calcium Increased Excretion of Phosphate Kidney Damage (Fanconi-like Syndrome) Increased Excretion of Phosphate Tenofovir/FTCLow Vitamin D CONCEPTUAL MODEL DEMOGRAPHICS25(OH)D & PTH 25(OH)D ng/ml >7060-7050-6040-5030-4020-3010-20<10 Percentage 50 40 30 20 10 0 Deficient Suboptimal Optimal Excessive 25(OH)D was suboptimal in 82% 25(OH)D > 30 ng/ml25(OH)D < 30 ng/ml 200 150 100 50 0 p=0.045 An IRB approved cross-sectional study with medical record review and interviews was done on 51 HIV-infected men taking anti-retroviral therapy (ART) with normal serum calcium. Blood 25(OH)D and PTH levels were assayed. TDF was always used with FTC. METHOD PTH pg/ml Fig 2b) Subjects on TDF/FTC: Those with 25(OH)D levels 30ng/ml Fig 3b) Subjects with suboptimal 25(OH)D: PTH levels were higher in subjects taking TDF/FTC than other ART Decreased Serum Calcium Supply Calcium at Cost to Bone Low Vitamin D Increased Parathyroid Hormone Secondary Hyperparathyroidism Osteoporosis Bone pain Muscle weakness Fatigue Cardiovascular disease Immunological impairments ART NOT TDF/FTC 200 150 100 50 0 TDF/FTC PTH pg/ml p=0.021 TDF/FTC IS ASSOCIATED WITH ELEVATED PTH 25(OH)D ng/ml PTH pg/ml 200 150 100 50 0 6050403020100 Fig 3a) PTH level is more dependant on 25(OH)D level in subjects on TDF/FTC than non-TDF/FTC ART 25(OH)D ng/ml 6050403020100 PTH pg/ml 200 150 100 50 0 Fig 2a) PTH levels among subjects taking TDF/FTC ART TDF/FTC ART, low 25(OH)D TDF/FTC ART, optimal 25(OH)D 25(OH)D ng/ml 6050403020100 PTH pg/ml 200 150 100 50 0 Non-TDF/FTC ART Fig 1) PTH levels among subjects taking non-TDF/FTC ART Non-TDF/FTC ART TDF/FTC ART a For continous variables, value is median (interquartile range) PTH Upper Limit Normal Lower Limit Optimal 25(OH)D Many subjects on TDF/FTC had PTH above the ULN