Continued Interest and Controversy: Vitamin D in HIV

1.

Escota GV, Cross S, Powderly WG. Vitamin D and calcium abnormalities in the HIV-infected population. Endocrinol Metab Clin N Am. 2014;43(3):743–67. https://doi.org/10.1016/j.ecl.2014.05.005.CrossRef

2.

Taylor CL, Sempos CT, Davis CD, Brannon PM. Vitamin D: moving forward to address emerging science. Nutrients. 2017;9(12) https://doi.org/10.3390/nu9121308.

3.

Holick MF. Vitamin D deficiency. N Engl J Med. 2007;357(3):266–81. https://doi.org/10.1056/NEJMra070553.PubMedCrossRef

4.

Guessous I. Role of vitamin D deficiency in extraskeletal complications: predictor of health outcome or marker of health status? Biomed Res Int. 2015;2015:563403. https://doi.org/10.1155/2015/563403.PubMedPubMedCentralCrossRef

5.

Coelho L, Cardoso SW, Luz PM, Hoffman RM, Mendonca L, Veloso VG, et al. Vitamin D3 supplementation in HIV infection: effectiveness and associations with antiretroviral therapy. Nutr J. 2015;14:81. https://doi.org/10.1186/s12937-015-0072-6.PubMedPubMedCentralCrossRef

6.

Aurpibul L, Sricharoenchai S, Wittawatmongkol O, Sirisanthana V, Phongsamart W, Sudjaritruk T, et al. Vitamin D status in perinatally HIV-infected Thai children receiving antiretroviral therapy. J Pediatr Endocrinol Metab. 2016;29(4):407–11. https://doi.org/10.1515/jpem-2015-0203.PubMedCrossRef

7.

Adeyemi OM, Agniel D, French AL, Tien PC, Weber K, Glesby MJ, et al. Vitamin D deficiency in HIV-infected and HIV-uninfected women in the United States. J Acquir Immune Defic Syndr. 2011;57(3):197–204. https://doi.org/10.1097/QAI.0b013e31821ae418.PubMedPubMedCentralCrossRef

8.

Bhan I. Vitamin d binding protein and bone health. Int J Endocrinol. 2014;2014:561214. https://doi.org/10.1155/2014/561214.PubMedPubMedCentralCrossRef

9.

Chun RF. New perspectives on the vitamin D binding protein. Cell Biochem Funct. 2012;30(6):445–56. https://doi.org/10.1002/cbf.2835.PubMedCrossRef

10.

Holick MF. The vitamin D deficiency pandemic: approaches for diagnosis, treatment and prevention. Rev Endocr Metab Disord. 2017;18(2):153–65. https://doi.org/10.1007/s11154-017-9424-1.PubMedCrossRef

11.

Binkley N, Ramamurthy R, Krueger D. Low vitamin D status: definition, prevalence, consequences, and correction. Rheum Dis Clin N Am. 2012;38(1):45–59. https://doi.org/10.1016/j.rdc.2012.03.006.CrossRef

12.

Powe CE, Ricciardi C, Berg AH, Erdenesanaa D, Collerone G, Ankers E, et al. Vitamin D-binding protein modifies the vitamin D-bone mineral density relationship. J Bone Miner Res. 2011;26(7):1609–16. https://doi.org/10.1002/jbmr.387.PubMedPubMedCentralCrossRef

13.

Bischoff-Ferrari HA, Orav EJ, Dawson-Hughes B. Effect of cholecalciferol plus calcium on falling in ambulatory older men and women: a 3-year randomized controlled trial. Arch Intern Med. 2006;166(4):424–30. https://doi.org/10.1001/archinte.166.4.424.PubMedCrossRef

14.

Cauley JA, Danielson ME, Boudreau R, Barbour KE, Horwitz MJ, Bauer DC, et al. Serum 25-hydroxyvitamin D and clinical fracture risk in a multiethnic cohort of women: the women’s health initiative (WHI). J Bone Miner Res. 2011;26(10):2378–88. https://doi.org/10.1002/jbmr.449.PubMedPubMedCentralCrossRef

15.

Cauley JA, Parimi N, Ensrud KE, Bauer DC, Cawthon PM, Cummings SR, et al. Serum 25-hydroxyvitamin D and the risk of hip and nonspine fractures in older men. J Bone Miner Res. 2010;25(3):545–53. https://doi.org/10.1359/jbmr.090826.PubMedCrossRef

16.

Holvik K, Ahmed LA, Forsmo S, Gjesdal CG, Grimnes G, Samuelsen SO, et al. Low serum levels of 25-hydroxyvitamin D predict hip fracture in the elderly: a NOREPOS study. J Clin Endocrinol Metab. 2013;98(8):3341–50. https://doi.org/10.1210/jc.2013-1468.PubMedCrossRef

17.

•• Reid IR, Horne AM, Mihov B, Gamble GD, Al-Abuwsi F, Singh M et al. Effect of monthly high-dose vitamin D on bone density in community-dwelling older adults substudy of a randomized controlled trial. J Intern Med. 2017;282(5):452–60. https://doi.org/10.1111/joim.12651. This was a two-year substudy of a randomized controlled trial of older community-dwelling adults who received monthly vitamin D3 (100,000 IU) versus placebo, focused on examining the impact of supplementation on lumbar spine BMD, and exploring thresholds of baseline 25OHD levels for vitamin D effects on BMD.

18.

Snijder MB, van Schoor NM, Pluijm SM, van Dam RM, Visser M, Lips P. Vitamin D status in relation to one-year risk of recurrent falling in older men and women. J Clin Endocrinol Metab. 2006;91(8):2980–5. https://doi.org/10.1210/jc.2006-0510.PubMedCrossRef

19.

IOM. Dietary reference intakes for calcium and vitamin D. Committee to Review Dietary Reference Intakes for Calcium and Vitamin D: Institute of Medicine2011.

20.

Valcour A, Blocki F, Hawkins DM, Rao SD. Effects of age and serum 25-OH-vitamin D on serum parathyroid hormone levels. J Clin Endocrinol Metab. 2012;97(11):3989–95. https://doi.org/10.1210/jc.2012-2276.PubMedCrossRef

21.

Holick MF, Siris ES, Binkley N, Beard MK, Khan A, Katzer JT, et al. Prevalence of vitamin D inadequacy among postmenopausal North American women receiving osteoporosis therapy. J Clin Endocrinol Metab. 2005;90(6):3215–24. https://doi.org/10.1210/jc.2004-2364.PubMedCrossRef

22.

Murad MH, Elamin KB, Abu Elnour NO, Elamin MB, Alkatib AA, Fatourechi MM, et al. Clinical review: the effect of vitamin D on falls: a systematic review and meta-analysis. J Clin Endocrinol Metab. 2011;96(10):2997–3006. https://doi.org/10.1210/jc.2011-1193.PubMedCrossRef

23.

Cervero M, Agud JL, Garcia-Lacalle C, Alcazar V, Torres R, Jusdado JJ, et al. Prevalence of vitamin D deficiency and its related risk factor in a Spanish cohort of adult HIV-infected patients: effects of antiretroviral therapy. AIDS Res Hum Retrovir. 2012;28(9):963–71. https://doi.org/10.1089/AID.2011.0244.PubMedCrossRef

24.

• Klassen KM, Fairley CK, Kimlin MG, Hocking J, Kelsall L, Ebeling PR. Vitamin D deficiency is common in HIV-infected southern Australian adults. Antivir Ther. 2016;21(2):117–25. https://doi.org/10.3851/IMP2983. This large cross-sectional study compared 25OHD levels among HIV-infected and uninfected indiviuals from Melbourne to examine the relationship between HIV status and vitamin D deficiency.

25.

• Jao J, Freimanis L, Mussi-Pinhata MM, Cohen RA, Monteiro JP, Cruz ML et al. Low vitamin D status among pregnant Latin American and Caribbean women with HIV Infection. Int J Gynaecol Obstet. 2015;130(1):54–8. https://doi.org/10.1016/j.ijgo.2015.01.017. This multi-center cross-sectional study evaluated prevalance and predictors of low vitamin D status among pregnant women with HIV from 17 sites in Latin America and the Caribbean.

26.

• Atteritano M, Mirarchi L, Venanzi-Rullo E, Santoro D, Iaria C, Catalano A et al. Vitamin D status and the relationship with bone fragility fractures in HIV-infected patients: a case control study. Int J Mol Sci. 2018;19(1). https://doi.org/10.3390/ijms19010119. This was a study evaluating prevalence of vertebral fractures and association with vitamin D status and ultrasound-based bone mineral density measures among 100 HIV-infected and 100 HIV-uninfected controls.

27.

Schtscherbyna A, Gouveia C, Pinheiro MF, Luiz RR, Farias ML, Machado ES. Vitamin D status in a Brazilian cohort of adolescents and young adults with perinatally acquired human immunodeficiency virus infection. Mem Inst Oswaldo Cruz. 2016;111(2):128–33. https://doi.org/10.1590/0074-02760150403.PubMedPubMedCentralCrossRef

28.

Hileman CO, Overton ET, McComsey GA. Vitamin D and bone loss in HIV. Curr Opin HIV AIDS. 2016;11(3):277–84. https://doi.org/10.1097/COH.0000000000000272.PubMedPubMedCentralCrossRef

29.

Hidron AI, Hill B, Guest JL, Rimland D. Risk factors for vitamin D deficiency among veterans with and without HIV infection. PLoS One. 2015;10(4):e0124168. https://doi.org/10.1371/journal.pone.0124168.PubMedPubMedCentralCrossRef

30.

Dao CN, Patel P, Overton ET, Rhame F, Pals SL, Johnson C, et al. Low vitamin D among HIV-infected adults: prevalence of and risk factors for low vitamin D Levels in a cohort of HIV-infected adults and comparison to prevalence among adults in the US general population. Clin Infect Dis. 2011;52(3):396–405. https://doi.org/10.1093/cid/ciq158.PubMedCrossRef

31.

Gois PHF, Ferreira D, Olenski S, Seguro AC. Vitamin D and infectious diseases: simple bystander or contributing factor? Nutrients. 2017;9(7). https://doi.org/10.3390/nu9070651.

32.

Mansueto P, Seidita A, Vitale G, Gangemi S, Iaria C, Cascio A. Vitamin D deficiency in HIV infection: not only a bone disorder. Biomed Res Int. 2015;2015:735615. https://doi.org/10.1155/2015/735615.PubMedPubMedCentralCrossRef

33.

Mehta S, Giovannucci E, Mugusi FM, Spiegelman D, Aboud S, Hertzmark E, et al. Vitamin D status of HIV-infected women and its association with HIV disease progression, anemia, and mortality. PLoS One. 2010;5(1):e8770. https://doi.org/10.1371/journal.pone.0008770.PubMedPubMedCentralCrossRef

34.

Mehta S, Mugusi FM, Spiegelman D, Villamor E, Finkelstein JL, Hertzmark E, et al. Vitamin D status and its association with morbidity including wasting and opportunistic illnesses in HIV-infected women in Tanzania. AIDS Patient Care STDs. 2011;25(10):579–85. https://doi.org/10.1089/apc.2011.0182.PubMedPubMedCentralCrossRef

35.

• Sudfeld CR, Duggan C, Aboud S, Kupka R, Manji KP, Kisenge R et al. Vitamin D status is associated with mortality, morbidity, and growth failure among a prospective cohort of HIV-infected and HIV-exposed Tanzanian infants. J Nutr. 2015;145(1):121–7. https://doi.org/10.3945/jn.114.201566. This prospective cohort study measured the association between vitamin D status and mortality, morbidity and growth during the first two years of life among HIV-infected and HIV-exposed infants in Tanzania.

36.

Sudfeld CR, Giovannucci EL, Isanaka S, Aboud S, Mugusi FM, Wang M, et al. Vitamin D status and incidence of pulmonary tuberculosis, opportunistic infections, and wasting among HIV-infected Tanzanian adults initiating antiretroviral therapy. J Infect Dis. 2013;207(3):378–85. https://doi.org/10.1093/infdis/jis693.PubMedCrossRef

37.

• Nylen H, Habtewold A, Makonnen E, Yimer G, Bertilsson L, Burhenne J et al. Prevalence and risk factors for efavirenz-based antiretroviral treatment-associated severe vitamin D deficiency: a prospective cohort study. Medicine (Baltimore). 2016;95(34):e4631. https://doi.org/10.1097/MD.0000000000004631. This was a prospective, comparative, observational study of HIV-TB co-infected versus HIV-monoinfected patients treated with efavirenz-based combination ART, focused on evaluating the impact of rifampin-based TB on efavienz-associated vitamin D deficiency over 48 weeks.

38.

Viard JP, Souberbielle JC, Kirk O, Reekie J, Knysz B, Losso M, et al. Vitamin D and clinical disease progression in HIV infection: results from the EuroSIDA study. AIDS. 2011;25(10):1305–15. https://doi.org/10.1097/QAD.0b013e328347f6f7.PubMedCrossRef

39.

Theodorou M, Serste T, Van Gossum M, Dewit S. Factors associated with vitamin D deficiency in a population of 2044 HIV-infected patients. Clin Nutr. 2014;33(2):274–9. https://doi.org/10.1016/j.clnu.2013.04.018.PubMedCrossRef

40.

Shiau S, Broun EC, Arpadi SM, Yin MT. Incident fractures in HIV-infected individuals: a systematic review and meta-analysis. AIDS. 2013;27(12):1949–57. https://doi.org/10.1097/QAD.0b013e328361d241.PubMedPubMedCentralCrossRef

41.

Triant VA, Brown TT, Lee H, Grinspoon SK. Fracture prevalence among human immunodeficiency virus (HIV)-infected versus non-HIV-infected patients in a large U.S. healthcare system. J Clin Endocrinol Metab. 2008;93(9):3499–504. https://doi.org/10.1210/jc.2008-0828.PubMedPubMedCentralCrossRef

42.

• Dave JA, Cohen K, Micklesfield LK, Maartens G, Levitt NS. Antiretroviral therapy, especially efavirenz, is associated with low bone mineral density in HIV-infected South Africans. PLoS One. 2015;10(12):e0144286. https://doi.org/10.1371/journal.pone.0144286. This was a cross-sectional study evaluating BMD and 25OHD levels in ART-treated versus ART-naïve HIV-positive adults in South Africa, focused on identifying factors associated with lower BMD in this population.

43.

Stellbrink HJ, Orkin C, Arribas JR, Compston J, Gerstoft J, Van Wijngaerden E, et al. Comparison of changes in bone density and turnover with abacavir-lamivudine versus tenofovir-emtricitabine in HIV-infected adults: 48-week results from the ASSERT study. Clin Infect Dis. 2010;51(8):963–72. https://doi.org/10.1086/656417.PubMedCrossRef

44.

McComsey GA, Kitch D, Daar ES, Tierney C, Jahed NC, Tebas P, et al. Bone mineral density and fractures in antiretroviral-naive persons randomized to receive abacavir-lamivudine or tenofovir disoproxil fumarate-emtricitabine along with efavirenz or atazanavir-ritonavir: Aids Clinical Trials Group A5224s, a substudy of ACTG A5202. J Infect Dis. 2011;203(12):1791–801. https://doi.org/10.1093/infdis/jir188.PubMedPubMedCentralCrossRef

45.

Brown TT, McComsey GA, King MS, Qaqish RB, Bernstein BM, da Silva BA. Loss of bone mineral density after antiretroviral therapy initiation, independent of antiretroviral regimen. J Acquir Immune Defic Syndr. 2009;51(5):554–61. https://doi.org/10.1097/QAI.0b013e3181adce44.PubMedCrossRef

46.

•• Tinago W, Cotter AG, Sabin CA, Macken A, Kavanagh E, Brady JJ et al. Predictors of longitudinal change in bone mineral density in a cohort of HIV-positive and negative patients. Aids. 2017;31(5):643-52. https://doi.org/10.1097/qad.0000000000001372. This was a prospective three-year cohort study examining longitudinal rate of decline and predictors of decline among HIV-positive and HIV-negative individuals.

47.

•• Gonciulea A, Wang R, Althoff KN, Palella FJ, Lake J, Kingsley LA et al. An increased rate of fracture occurs a decade earlier in HIV+ compared with HIV− men. AIDS. 2017;31(10):1435–43. https://doi.org/10.1097/QAD.0000000000001493. This was an analysis of data from the Multicenter AIDS Cohort Study, a large prospective multi-center cohort study of HIV-positive and HIV-negative men to determine predictors of incident fracture.

48.

Sharma A, Shi Q, Hoover DR, Anastos K, Tien PC, Young MA, et al. Increased fracture incidence in middle-aged HIV-infected and HIV-uninfected women: updated results from the Women’s Interagency HIV Study. J Acquir Immune Defic Syndr. 2015;70(1):54–61. https://doi.org/10.1097/qai.0000000000000674.PubMedPubMedCentralCrossRef

49.

Yin MT, Kendall MA, Wu X, Tassiopoulos K, Hochberg M, Huang JS, et al. Fractures after antiretroviral initiation. AIDS. 2012;26(17):2175–84. https://doi.org/10.1097/QAD.0b013e328359a8ca.PubMedPubMedCentralCrossRef

50.

•• Erlandson KM, Lake JE, Sim M, Falutz J, Prado CM, Domingues da Silva AR et al. Bone mineral density declines twice as quickly among HIV-infected women compared to men. J Acquir Immune Defic Syndr. 2017. https://doi.org/10.1097/QAI.0000000000001591. This was a large prospective cohort study of HIV-infected Italian men and women examining long-term changes (up to 10 years of follow-up, median 4.6 years) and risk factors for decline in BMD after ART initiation.

51.

• Sudjaritruk T, Bunupuradah T, Aurpibul L, Kosalaraksa P, Kurniati N, Prasitsuebsai W et al. Hypovitaminosis D and hyperparathyroidism: effects on bone turnover and bone mineral density among perinatally HIV-infected adolescents. AIDS. 2016;30(7):1059–67. https://doi.org/10.1097/QAD.0000000000001032. This was a multi-center, cross-sectional study evaluating bone mineral density, bone turnover, hypovitaminosis D and hyperparathyroidism among perinatally HIV-infected adolescents in a tropical region (Thailand and Indonesia).

52.

• Jacobson DL, Stephensen CB, Miller TL, Patel K, Chen JS, Van Dyke RB et al. Associations of low Vitamin D and elevated parathyroid hormone concentrations with bone mineral density in perinatally HIV-infected children. J Acquir Immune Defic Syndr. 2017;76(1):33–42. https://doi.org/10.1097/QAI.0000000000001467. This was a cross-sectional analysis of data from the Adolescent Master Protocol of the Pediatric HIV/AIDS Cohort Study focused on comparing bone mineral density, 25OHD and parathyroid hormone levels among perinatally HV-infected children versus perinatally HIV exposed uninfected children.

53.

• Eckard AR, Thierry-Palmer M, Silvestrov N, Rosebush JC, O'Riordan MA, Daniels JE et al. Effects of cholecalciferol supplementation on serum and urinary vitamin D metabolites and binding protein in HIV-infected youth. J Steroid Biochem Mol Biol. 2017;168:38–48. https://doi.org/10.1016/j.jsbmb.2017.01.018. This randomized controlled trial evaluated changes in vitamin D metabolites and binding protein among HIV-infected versus HIV-uninfected youth after 6 months of supplementation with monthly medium- (60,000IU), or high- (120,000IU) dose vitamin D3, compared with low-dose (18,000 IU) supplementation.

54.

Lerma-Chippirraz E, Guerri-Fernandez R, Villar Garcia J, Gonzalez Mena A, Guelar Grinberg A, Montero MM, et al. Validation protocol of vitamin D supplementation in patients with HIV-Infection. AIDS Research and Treatment. 2016;2016:5120831. https://doi.org/10.1155/2016/5120831.PubMedPubMedCentralCrossRef

55.

Lake JE, Hoffman RM, Tseng CH, Wilhalme HM, Adams JS, Currier JS. Success of standard dose vitamin D supplementation in treated human immunodeficiency virus infection. Open Forum Infect Dis. 2015;2(2):ofv068. https://doi.org/10.1093/ofid/ofv068.PubMedPubMedCentralCrossRef

56.

•• Overton ET, Chan ES, Brown TT, Tebas P, McComsey GA, Melbourne KM et al. Vitamin D and calcium attenuate bone loss with antiretroviral therapy initiation: a randomized trial. Ann Intern Med. 2015;162(12):815–24. https://doi.org/10.7326/M14-1409. This is an analysis of data from the ACTG A5280 Study of high-dose vitamin D3 plus calcium supplementation versus placebo, focused on the impact of supplementation on bone mineral density and biomarkers of bone metabolism and inflammation over 48 weeks after ART initiation.

57.

• Eckard AR, O'Riordan MA, Rosebush JC, Ruff JH, Chahroudi A, Labbato D et al. Effects of vitamin D supplementation on bone mineral density and bone markers in HIV-infected youth. J Acquir Immune Defic Syndr. 2017;76(5):539–46. https://doi.org/10.1097/qai.0000000000001545. This randomized controlled trial evaluated changes in BMD and bone turnover markers among HIV-infected youth with vitamin D insufficiency after 12 months of supplementation with monthly medium- (60,000IU), or high- (120,000IU) dose vitamin D3, compared with a standard/control dose (18,000 IU).

58.

Banon S, Rosillo M, Gomez A, Perez-Elias MJ, Moreno S, Casado JL. Effect of a monthly dose of calcidiol in improving vitamin D deficiency and secondary hyperparathyroidism in HIV-infected patients. Endocrine. 2015;49(2):528–37. https://doi.org/10.1007/s12020-014-0489-2.PubMedCrossRef

59.

•• Havens PL, Stephensen CB, Van Loan MD, Schuster GU, Woodhouse LR, Flynn PM et al. Vitamin D3 supplementation increases spine bone mineral density in adolescents and young adults with human immunodeficiency virus infection being treated with tenofovir disoproxil fumarate: a randomized, placebo-controlled trial. Clin Infect Dis. 2018;66(2):220–8. https://doi.org/10.1093/cid/cix753. This was a randomized, double-blind, placebo-controlled trial evaluating the impact of directly observed vitamin D3 supplementation (50,000IU every 4 weeks) versus placebo among HIV-positive youth initiating tenofovir-based ART on percent change in bone mineral density at the lumbar spine.

60.

Rovner AJ, Stallings VA, Rutstein R, Schall JI, Leonard MB, Zemel BS. Effect of high-dose cholecalciferol (vitamin D3) on bone and body composition in children and young adults with HIV infection: a randomized, double-blind, placebo-controlled trial. Osteoporos Int. 2017;28(1):201–9. https://doi.org/10.1007/s00198-016-3826-x.PubMedCrossRef

61.

Bolland MJ, Grey AB, Horne AM, Briggs SE, Thomas MG, Ellis-Pegler RB, et al. Annual zoledronate increases bone density in highly active antiretroviral therapy-treated human immunodeficiency virus-infected men: a randomized controlled trial. J Clin Endocrinol Metab. 2007;92(4):1283–8. https://doi.org/10.1210/jc.2006-2216.PubMedCrossRef

62.

Guaraldi G, Orlando G, Madeddu G, Vescini F, Ventura P, Campostrini S, et al. Alendronate reduces bone resorption in HIV-associated osteopenia/osteoporosis. HIV clinical trials. 2004;5(5):269–77. https://doi.org/10.1310/md8v-5dlg-en3t-brhx.PubMedCrossRef

63.

Huang J, Meixner L, Fernandez S, McCutchan JA. A double-blinded, randomized controlled trial of zoledronate therapy for HIV-associated osteopenia and osteoporosis. AIDS. 2009;23(1):51–7. https://doi.org/10.1097/QAD.0b013e32831c8adc.PubMedPubMedCentralCrossRef

64.

McComsey GA, Kendall MA, Tebas P, Swindells S, Hogg E, Alston-Smith B, et al. Alendronate with calcium and vitamin D supplementation is safe and effective for the treatment of decreased bone mineral density in HIV. AIDS. 2007;21(18):2473–82. https://doi.org/10.1097/QAD.0b013e3282ef961d.PubMedCrossRef

65.

Mondy K, Powderly WG, Claxton SA, Yarasheski KH, Royal M, Stoneman JS, et al. Alendronate, vitamin D, and calcium for the treatment of osteopenia/osteoporosis associated with HIV infection. J Acquir Immune Defic Syndr. 2005;38(4):426–31.PubMedCrossRef

66.

Negredo E, Bonjoch A, Perez-Alvarez N, Ornelas A, Puig J, Herrero C, et al. Comparison of two different strategies of treatment with zoledronate in HIV-infected patients with low bone mineral density: single dose versus two doses in 2 years. HIV Med. 2015;16(7):441–8. https://doi.org/10.1111/hiv.12260.PubMedCrossRef

67.

Rozenberg S, Lanoy E, Bentata M, Viard JP, Valantin MA, Missy P, et al. Effect of alendronate on HIV-associated osteoporosis: a randomized, double-blind, placebo-controlled, 96-week trial (ANRS 120). AIDS Res Hum Retrovir. 2012;28(9):972–80. https://doi.org/10.1089/aid.2011.0224.PubMedCrossRef

68.

Dhaliwal R, Aloia JF. Effect of vitamin D on falls and physical performance. Endocrinol Metab Clin N Am. 2017;46(4):919–33. https://doi.org/10.1016/j.ecl.2017.07.004.CrossRef

69.

Koundourakis NE, Avgoustinaki PD, Malliaraki N, Margioris AN. Muscular effects of vitamin D in young athletes and non-athletes and in the elderly. Hormones (Athens, Greece). 2016;15(4):471–88. https://doi.org/10.14310/horm.2002.1705.CrossRef

70.

• Brown JC, Schall JI, Rutstein RM, Leonard MB, Zemel BS, Stallings VA. The impact of vitamin D3 supplementation on muscle function among HIV-infected children and young adults: a randomized controlled trial. J Musculoskelet Neuronal Interact. 2015;15(2):145–53. This study analyzed data from a small randomized controlled trial of 12 months of daily vitamin D3 supplementation (7000IU) versus placebo and uniquely examines the impact of supplementation on neuromuscular motor skills and muscle function.

71.

Cozzolino M, Vidal M, Arcidiacono MV, Tebas P, Yarasheski KE, Dusso AS. HIV-protease inhibitors impair vitamin D bioactivation to 1,25-dihydroxyvitamin D. AIDS. 2003;17(4):513–20. https://doi.org/10.1097/01.aids.0000050817.06065.f8.PubMedCrossRef

72.

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74.

•• Avihingsanon A, Kerr SJ, Ramautarsing RA, Praditpornsilpa K, Sophonphan J, Ubolyam S et al. The association of gender, age, efavirenz use, and hypovitaminosis d among hiv-infected adults living in the tropics. AIDS Res Hum Retroviruses. 2016;32(4):317–24. https://doi.org/10.1089/AID.2015.0069. This was a cross-sectional study evaluating levels of hypovitaminosis D among patients with HIV in a tropical region (Thailand) and factor associated with low levels of 25OHD.

75.

Gyllensten K, Josephson F, Lidman K, Saaf M. Severe vitamin D deficiency diagnosed after introduction of antiretroviral therapy including efavirenz in a patient living at latitude 59 degrees N. AIDS. 2006;20(14):1906–7. https://doi.org/10.1097/01.aids.0000244216.08327.39.PubMedCrossRef

76.

Wang Z, Schuetz EG, Xu Y, Thummel KE. Interplay between vitamin D and the drug metabolizing enzyme CYP3A4. J Steroid Biochem Mol Biol. 2013;136:54–8. https://doi.org/10.1016/j.jsbmb.2012.09.012.PubMedCrossRef

77.

Ward BA, Gorski JC, Jones DR, Hall SD, Flockhart DA, Desta Z. The cytochrome P450 2B6 (CYP2B6) is the main catalyst of efavirenz primary and secondary metabolism: implication for HIV/AIDS therapy and utility of efavirenz as a substrate marker of CYP2B6 catalytic activity. J Pharmacol Exp Ther. 2003;306(1):287–300. https://doi.org/10.1124/jpet.103.049601.PubMedCrossRef

78.

Wyen C, Hendra H, Siccardi M, Platten M, Jaeger H, Harrer T, et al. Cytochrome P450 2B6 (CYP2B6) and constitutive androstane receptor (CAR) polymorphisms are associated with early discontinuation of efavirenz-containing regimens. J Antimicrob Chemother. 2011;66(9):2092–8. https://doi.org/10.1093/jac/dkr272.PubMedCrossRef

79.

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