This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Tenofovir, with a favorable kinetics profile that allows it to be administered once daily, is important in the care of adolescents with HIV. However, tenofovir administration is associated with increase in PTH and other markers of bone turnover, decrease in TRP with renal phosphate wasting, and decrease in BMD. If there is a way to overcome the effects of tenofovir on renal phosphate loss or on the markers of bone turnover like PTH or BAP, or a way to reverse the decrease in BMD seen with tenofovir use and thereby show reversal of the deleterious effects of the drug on bone, perhaps more children and adolescents would be able to benefit from this potent drug as part of once daily regimens in therapy for HIV infection. Vitamin D has the physiologic effect of decreasing PTH and other markers of bone turnover, decreasing renal phosphate loss, and increasing BMD. In this study, the effect of an every four week dose of vitamin D3 on changes in calcium, phosphate, and bone metabolism in adolescents and young adults with HIV infection who are being treated with ART that includes tenofovir will be measured and compared with the effects of the vitamin D supplementation on changes in a group being treated with ART not containing tenofovir, and with subjects receiving vitamin D placebo as controls for both tenofovir and non-tenofovir groups. Covariates of interest include age, gender, race, BSA, BMI, tenofovir exposure (AUC), duration of HIV infection and its treatment, and plasma viral load, as well as administration of other antiretrovirals. This study tests the hypothesis that, in a population of HIV-infected adolescents and young adults treated with tenofovir as part of an ARV combination regimen, vitamin D supplementation will: Decrease renal phosphate loss; Decrease plasma PTH;and Improve other markers of bone turnover. Doses of vitamin D given at four-week intervals will act to normalize these values in the tenofovir-treated group so that the calcium-phosphate-bone turnover marker status of the group whose ARV regimen contains tenofovir will be comparable to that of the group whose ARV regimen does not contain tenofovir by 12 weeks of supplementation. Primary Objectives: To compare the change in renal tubular reabsorption of phosphate (measured as TRP, TmP/GFR, and PO4/Cr) and markers of bone turnover (BAP, NTX, and PTH) in adolescents and young adults with HIV whose ARV combination regimen contains tenofovir, to the change in values in those whose ARV combination therapy does not contain tenofovir, and to measure the effect of vitamin D or placebo on those changes within and between the four study groups, during 12 weeks of treatment with vitamin D3, 50,000 IU administered orally once every four weeks. To measure the safety of 50,000 IU dose of vitamin D3 when administered orally every 4 weeks for 12 weeks in adolescents and young adults with HIV treated or not treated with tenofovir-containing ARV combination therapy by evaluating the change in serum calcium and urine calcium/creatinine ratio at four-week intervals.
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