Vitamin D and Calcium Supplement Attenuate Bone Loss among HIVInfected Patients Receiving Tenofovir Disoproxil Fumarate/Emtricitabine/ Efavirenz: An Open-Label, Randomized Controlled Trial

Author(s): Patawee Boontanondha, Hataikarn Nimitphong, Suchawadee Musikarat, Aschara Ragkho, Sasisopin Kiertiburanakul*

Journal Name: Current HIV Research

Volume 18 , Issue 1 , 2020

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Graphical Abstract:


Abstract:

Background: Antiretroviral therapy (ART), especially with tenofovir disoproxil fumarate (TDF), has been associated with accelerated bone turnover and leads to significant bone loss.

Objective: We aimed to determine the effect of vitamin D2 and calcium on bone mineral density (BMD) in HIV-infected patients receiving TDF/emtricitabine (FTC)/efavirenz (EFV).

Methods: A prospective, open-label, randomized controlled study was conducted. Eligible patients were ART naïve HIV individuals who initiated TDF/FTC/EFV. The study group received supplementation with vitamin D2 and calcium carbonate, whereas the control group was administered only ART. The primary outcome was the percentage change in total hip BMD at week 24 compared with baseline.

Results: A total of 18 patients were randomized (9 in each group). The mean (standard deviation; SD) total hip BMD significantly decreased from baseline in both groups, from 0.96 (0.14) g/cm2 to 0.93 (0.13) g/cm2 in the study group (p = 0.006) and from 0.87 (0.11) g/cm2 to 0.84 (0.11) g/cm2 in the control group (p = 0.004). The mean (SD) lumbar spine BMD significantly decreased from baseline in both groups, from 1.00 (0.13) g/cm2 to 0.97 (0.13) g/cm2 (p = 0.004) in the study group and from 0.90 (0.09) g/cm3 to 0.86 (0.08) g/cm2 in the control group (p = 0.006). At week 24, the mean (SD) lumbar spine BMD was significantly greater in the study group than in the control group (p = 0.042). However, there were no significant differences in the percentage change of total hip, lumbar spine, and femoral neck BMD between both groups. No adverse events were reported. In conclusion, as early as 24 weeks after TDF initiation, a significant decline in BMD was detected.

Conclusion: Vitamin D2 and calcium supplements should be considered for HIV-infected patients receiving TDF/FTC/EFV in a resource-limited setting where there are limited ART options (Clinicaltrials. gov NCT0287643).

Keywords: Bone loss, bone mineral density, calcium, HIV, tenofovir disoproxil fumarate, vitamin D.

[1]
Survival of HIV-positive patients starting antiretroviral therapy between 1996 and 2013: A collaborative analysis of cohort studies. Lancet HIV 2017; 4(8): e349-56.
[http://dx.doi.org/10.1016/S2352-3018(17)30066-8] [PMID: 28501495]
[2]
May MT, Gompels M, Delpech V, et al. UK Collaborative HIV Cohort (UK CHIC) Study. Impact on life expectancy of HIV-1 positive individuals of CD4+ cell count and viral load response to antiretroviral therapy. AIDS 2014; 28(8): 1193-202.
[http://dx.doi.org/10.1097/QAD.0000000000000243] [PMID: 24556869]
[3]
Nakagawa F, Lodwick RK, Smith CJ, et al. Projected life expectancy of people with HIV according to timing of diagnosis. AIDS 2012; 26(3): 335-43.
[http://dx.doi.org/10.1097/QAD.0b013e32834dcec9] [PMID: 22089374]
[4]
Lundgren JD, Babiker AG, Gordin F, et al. INSIGHT START Study Group. Initiation of antiretroviral therapy in early asymptomatic HIV infection. N Engl J Med 2015; 373(9): 795-807.
[http://dx.doi.org/10.1056/NEJMoa1506816] [PMID: 26192873]
[5]
Stellbrink HJ, Orkin C, Arribas JR, et al. ASSERT Study Group. 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.
[http://dx.doi.org/10.1086/656417] [PMID: 20828304]
[6]
Haskelberg H, Hoy JF, Amin J, Ebeling PR, Emery S, Carr A. STEAL Study Group. Changes in bone turnover and bone loss in HIV-infected patients changing treatment to tenofovir-emtricitabine or abacavir-lamivudine. PLoS One 2012; 7(6)e38377
[http://dx.doi.org/10.1371/journal.pone.0038377] [PMID: 22719882]
[7]
Prior J, Burdge D, Maan E, et al. Fragility fractures and bone mineral density in HIV positive women: A case-control population-based study. Osteoporos Int 2007; 18(10): 1345-53.
[http://dx.doi.org/10.1007/s00198-007-0428-7] [PMID: 17665239]
[8]
Womack JA, Goulet JL, Gibert C, et al. Veterans Aging Cohort Study Project Team. Increased risk of fragility fractures among HIV infected compared to uninfected male veterans. PLoS One 2011; 6(2)e17217
[http://dx.doi.org/10.1371/journal.pone.0017217] [PMID: 21359191]
[9]
Young B, Dao CN, Buchacz K, Baker R, Brooks JT. HIV Outpatient Study (HOPS) Investigators. Increased rates of bone fracture among HIV-infected persons in the HIV Outpatient Study (HOPS) compared with the US general population, 2000-2006. Clin Infect Dis 2011; 52(8): 1061-8.
[http://dx.doi.org/10.1093/cid/ciq242] [PMID: 21398272]
[10]
Dao CN, Patel P, Overton ET, et al. Study to Understand the Natural History of HIV and AIDS in the Era of Effective Therapy (SUN) Investigators. 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.
[http://dx.doi.org/10.1093/cid/ciq158] [PMID: 21217186]
[11]
Ingle SM, May MT, Gill MJ, et al. Antiretroviral Therapy Cohort Collaboration. Impact of risk factors for specific causes of death in the first and subsequent years of antiretroviral therapy among HIV-infected patients. Clin Infect Dis 2014; 59(2): 287-97.
[http://dx.doi.org/10.1093/cid/ciu261] [PMID: 24771333]
[12]
Brown TT, Qaqish RB. Antiretroviral therapy and the prevalence of osteopenia and osteoporosis: A meta-analytic review. AIDS 2006; 20(17): 2165-74.
[http://dx.doi.org/10.1097/QAD.0b013e32801022eb] [PMID: 17086056]
[13]
Mills EJ, Bärnighausen T, Negin J. HIV and aging--preparing for the challenges ahead. N Engl J Med 2012; 366(14): 1270-3.
[http://dx.doi.org/10.1056/NEJMp1113643] [PMID: 22475591]
[14]
Yin MT, Brown TT. HIV and bone complications: understudied populations and new management strategies. Curr HIV/AIDS Rep 2016; 13(6): 349-58.
[http://dx.doi.org/10.1007/s11904-016-0341-9] [PMID: 27730445]
[15]
Prieto-Alhambra D, Güerri-Fernández R, De Vries F, et al. HIV infection and its association with an excess risk of clinical fractures: a nationwide case-control study. J Acquir Immune Defic Syndr 2014; 66(1): 90-5.
[http://dx.doi.org/10.1097/QAI.0000000000000112] [PMID: 24457634]
[16]
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.
[http://dx.doi.org/10.1097/QAD.0b013e328361d241] [PMID: 24126140]
[17]
Bedimo RJ, Adams-Huet B, Poindexter J, et al. The differential effects of human immunodeficiency virus and hepatitis C virus on bone microarchitecture and fracture risk. Clin Infect Dis 2018; 66(9): 1442-7.
[http://dx.doi.org/10.1093/cid/cix1011] [PMID: 29145609]
[18]
Bedimo R, Maalouf NM, Lo Re V III. Hepatitis C virus coinfection as a risk factor for osteoporosis and fracture. Curr Opin HIV AIDS 2016; 11(3): 285-93.
[http://dx.doi.org/10.1097/COH.0000000000000259] [PMID: 26890206]
[19]
Lo Re V III, Lynn K, Stumm ER, et al. Structural bone deficits in HIV/HCV-coinfected, HCV-monoinfected, and HIV-monoinfected women. J Infect Dis 2015; 212(6): 924-33.
[http://dx.doi.org/10.1093/infdis/jiv147] [PMID: 25754980]
[20]
Dong HV, Cortés YI, Shiau S, Yin MT. Osteoporosis and fractures in HIV/hepatitis C virus coinfection: A systematic review and meta-analysis. AIDS 2014; 28(14): 2119-31.
[http://dx.doi.org/10.1097/QAD.0000000000000363] [PMID: 24977441]
[21]
Starup-Linde J, Rosendahl SB, Storgaard M, Langdahl B. Management of osteoporosis in patients living with HIV-a systematic review and meta-analysis. J Acquir Immune Defic Syndr 2020; 83(1): 1-8.
[http://dx.doi.org/10.1097/QAI.0000000000002207] [PMID: 31809356]
[22]
Borderi M, Gibellini D, Vescini F, et al. Metabolic bone disease in HIV infection. AIDS 2009; 23(11): 1297-310.
[http://dx.doi.org/10.1097/QAD.0b013e32832ce85a] [PMID: 19550284]
[23]
Ofotokun I, McIntosh E, Weitzmann MN. HIV: inflammation and bone. Curr HIV/AIDS Rep 2012; 9(1): 16-25.
[http://dx.doi.org/10.1007/s11904-011-0099-z] [PMID: 22179898]
[24]
Hileman CO, Eckard AR, McComsey GA. Bone loss in HIV: A contemporary review. Curr Opin Endocrinol Diabetes Obes 2015; 22(6): 446-51.
[http://dx.doi.org/10.1097/MED.0000000000000200] [PMID: 26414081]
[25]
Oursler KK, Iranmanesh A, Jain C, et al. Low muscle mass is associated with osteoporosis in older adults living with HIV. AIDS Res Hum Retroviruses 2019. Epub ahead of print
[http://dx.doi.org/10.1089/aid.2019.0207] [PMID: 31762303]
[26]
Kooij KW, Wit FW, Bisschop PH, et al. Low bone mineral density in patients with well-suppressed HIV infection: association with body weight, smoking, and prior advanced HIV disease. J Infect Dis 2015; 211: 539: 48
[27]
Walker Harris V, Brown TT. Bone loss in the HIV-infected patient: evidence, clinical implications, and treatment strategies. J Infect Dis 2012; 205(Suppl. 3): S391-8.
[http://dx.doi.org/10.1093/infdis/jis199] [PMID: 22577213]
[28]
Gallant JE, Staszewski S, Pozniak AL, et al. 903 Study Group. Efficacy and safety of tenofovir DF vs stavudine in combination therapy in antiretroviral-naive patients: a 3-year randomized trial. JAMA 2004; 292(2): 191-201.
[http://dx.doi.org/10.1001/jama.292.2.191] [PMID: 15249568]
[29]
Duvivier C, Kolta S, Assoumou L, et al. ANRS 121 Hippocampe study group. Greater decrease in bone mineral density with protease inhibitor regimens compared with nonnucleoside reverse transcriptase inhibitor regimens in HIV-1 infected naive patients. AIDS 2009; 23(7): 817-24.
[http://dx.doi.org/10.1097/QAD.0b013e328328f789] [PMID: 19363330]
[30]
McComsey GA, Kitch D, Daar ES, 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.
[http://dx.doi.org/10.1093/infdis/jir188] [PMID: 21606537]
[31]
Martin A, Bloch M, Amin J, et al. Simplification of antiretroviral therapy with tenofovir-emtricitabine or abacavir-lamivudine: a randomized, 96-week trial. Clin Infect Dis 2009; 49(10): 1591-601.
[http://dx.doi.org/10.1086/644769] [PMID: 19842973]
[32]
Assoumou L, Katlama C, Viard JP, et al. ANRS Osteovir study group. Changes in bone mineral density over a 2-year period in HIV-1-infected men under combined antiretroviral therapy with osteopenia. AIDS 2013; 27(15): 2425-30.
[http://dx.doi.org/10.1097/QAD.0b013e32836378c3] [PMID: 24029735]
[33]
Overton ET, Chan ES, Brown TT, et al. Vitamin D and calcium attenuate bone loss with antiretroviral therapy initiation: A randomized trial. Ann Intern Med 2015; 162(12): 815-24.
[http://dx.doi.org/10.7326/M14-1409] [PMID: 26075752]
[34]
Mulligan K, Glidden DV, Anderson PL, et al. Preexposure Prophylaxis Initiative Study Team. Effects of emtricitabine/tenofovir on bone mineral density in HIV-negative persons in a randomized, double-blind, placebo-controlled trial. Clin Infect Dis 2015; 61(4): 572-80.
[http://dx.doi.org/10.1093/cid/civ324] [PMID: 25908682]
[35]
Woodward CL, Hall AM, Williams IG, et al. Tenofovir-associated renal and bone toxicity. HIV Med 2009; 10(8): 482-7.
[http://dx.doi.org/10.1111/j.1468-1293.2009.00716.x] [PMID: 19459988]
[36]
Grant PM, Cotter AG. Tenofovir and bone health. Curr Opin HIV AIDS 2016; 11(3): 326-32.
[http://dx.doi.org/10.1097/COH.0000000000000248] [PMID: 26859637]
[37]
Wiboonchutikul S, Sungkanuparph S, Kiertiburanakul S, et al. Vitamin D insufficiency and deficiency among HIV-1-infected patients in a tropical setting. J Int Assoc Physicians AIDS Care (Chic) 2012; 11(5): 305-10.
[http://dx.doi.org/10.1177/1545109711432142] [PMID: 22247338]
[38]
Wohl DA, Orkin C, Doroana M, et al. Change in vitamin D levels and risk of severe vitamin D deficiency over 48 weeks among HIV-1-infected, treatment-naive adults receiving rilpivirine or efavirenz in a Phase III trial (ECHO). Antivir Ther (Lond) 2014; 19(2): 191-200.
[http://dx.doi.org/10.3851/IMP2721] [PMID: 24430534]
[39]
Avihingsanon A, Kerr SJ, Ramautarsing RA, 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.
[http://dx.doi.org/10.1089/aid.2015.0069] [PMID: 26413903]
[40]
Welz T, Childs K, Ibrahim F, et al. Efavirenz is associated with severe vitamin D deficiency and increased alkaline phosphatase. AIDS 2010; 24(12): 1923-8.
[http://dx.doi.org/10.1097/QAD.0b013e32833c3281] [PMID: 20588161]
[41]
Cosman F, de Beur SJ, LeBoff MS, et al. National Osteoporosis Foundation. Clinician’s guide to prevention and treatment of osteoporosis. Osteoporos Int 2014; 25(10): 2359-81.
[http://dx.doi.org/10.1007/s00198-014-2794-2] [PMID: 25182228]
[42]
Moran CA, Weitzmann MN, Ofotokun I. The protease inhibitors and HIV-associated bone loss. Curr Opin HIV AIDS 2016; 11(3): 333-42.
[http://dx.doi.org/10.1097/COH.0000000000000260] [PMID: 26918650]
[43]
McComsey GA, Lupo S, Parks D, et al. 202094 Sub-Study Investigators. Switch from tenofovir disoproxil fumarate combination to dolutegravir with rilpivirine improves parameters of bone health. AIDS 2018; 32(4): 477-85.
[PMID: 29239893]
[44]
Brown TT, Moser C, Currier JS, et al. Changes in bone mineral density after initiation of antiretroviral treatment with tenofovir disoproxil fumarate/emtricitabine plus atazanavir/ritonavir, darunavir/ritonavir, or raltegravir. J Infect Dis 2015; 212(8): 1241-9.
[http://dx.doi.org/10.1093/infdis/jiv194] [PMID: 25948863]
[45]
Manosuthi W, Ongwandee S, Bhakeecheep S, et al. Adults and Adolescents Committee of the Thai National HIV Guidelines Working Group. Guidelines for antiretroviral therapy in HIV-1 infected adults and adolescents 2014, Thailand. AIDS Res Ther 2015; 12: 12.
[http://dx.doi.org/10.1186/s12981-015-0053-z] [PMID: 25908935]
[47]
Brown TT, Hoy J, Borderi M, et al. Recommendations for evaluation and management of bone disease in HIV. Clin Infect Dis 2015; 60(8): 1242-51.
[http://dx.doi.org/10.1093/cid/civ010] [PMID: 25609682]
[48]
Maartens G, Boffito M, Flexner CW. Compatibility of next-generation first-line antiretrovirals with rifampicin-based antituberculosis therapy in resource limited settings. Curr Opin HIV AIDS 2017; 12(4): 355-8.
[http://dx.doi.org/10.1097/COH.0000000000000376] [PMID: 28403028]
[49]
Panel on antiretroviral guidelines for adults and adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents [cited 2019 October 7] Available at http://aidsinfo.nih.gov/contentfiles/lvguidelines/AdultandAdolescentGL.pdf
[50]
Strategies for management of anti-retroviral therapy/INSIGHT1, DAD study groups. Use of nucleoside reverse transcriptase inhibitors and risk of myocardial infarction in HIV-infected patients. AIDS 2008; 22: F17-24.
[http://dx.doi.org/10.1097/QAD.0b013e32830fe35e]
[51]
Worm SW, Sabin C, Weber R, et al. Risk of myocardial infarction in patients with HIV infection exposed to specific individual antiretroviral drugs from the 3 major drug classes: The data collection on adverse events of anti-HIV drugs (D:A:D) study. J Infect Dis 2010; 201(3): 318-30.
[http://dx.doi.org/10.1086/649897] [PMID: 20039804]
[52]
Obel N, Farkas DK, Kronborg G, et al. Abacavir and risk of myocardial infarction in HIV-infected patients on highly active antiretroviral therapy: A population-based nationwide cohort study. HIV Med 2010; 11(2): 130-6.
[http://dx.doi.org/10.1111/j.1468-1293.2009.00751.x] [PMID: 19682101]
[53]
Nimitphong H, Samittarucksa R, Saetung S, Bhirommuang N, Chailurkit LO, Ongphiphadhanakul B. The effect of vitamin D supplementation on metabolic phenotypes in thais with prediabetes. J Med Assoc Thai 2015; 98(12): 1169-78.
[PMID: 27004301]
[54]
Sritara C, Thakkinstian A, Ongphiphadhanakul B, et al. Causal relationship between the AHSG gene and BMD through fetuin-A and BMI: multiple mediation analysis. Osteoporos Int 2014; 25(5): 1555-62.
[http://dx.doi.org/10.1007/s00198-014-2634-4] [PMID: 24570294]
[55]
Baim S, Binkley N, Bilezikian JP, et al. Official positions of the international society for clinical densitometry and executive summary of the 2007 ISCD position development conference. J Clin Densitom 2008; 11(1): 75-91.
[http://dx.doi.org/10.1016/j.jocd.2007.12.007] [PMID: 18442754]
[56]
Hozo SP, Djulbegovic B, Hozo I. Estimating the mean and variance from the median, range, and the size of a sample. BMC Med Res Methodol 2005; 5: 13.
[http://dx.doi.org/10.1186/1471-2288-5-13] [PMID: 15840177]
[57]
Cotter AG, Vrouenraets SM, Brady JJ, et al. PREPARE (Preventing Progression of Adipose Tissue Redistribution) Investigators. Impact of switching from zidovudine to tenofovir disoproxil fumarate on bone mineral density and markers of bone metabolism in virologically suppressed HIV-1 infected patients; a substudy of the PREPARE study. J Clin Endocrinol Metab 2013; 98(4): 1659-66.
[http://dx.doi.org/10.1210/jc.2012-3686] [PMID: 23436922]
[58]
Rasmussen TA, Jensen D, Tolstrup M, et al. Comparison of bone and renal effects in HIV-infected adults switching to abacavir or tenofovir based therapy in a randomized trial. PLoS One 2012; 7(3) :e32445
[http://dx.doi.org/10.1371/journal.pone.0032445] [PMID: 22479327]
[59]
World health organization.. Consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection. [cited 2019 October 7] Available at: http://www.who.int/ hiv/pub/guidelines/arv2013/download/en
[60]
Havens PL, Stephensen CB, Van Loan MD, et al. Adolescent Medicine Trials Network for HIV/AIDS Interventions (ATN) 109 Study Team. 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.
[http://dx.doi.org/10.1093/cid/cix753] [PMID: 29020329]
[61]
Bech A, Van Bentum P, Telting D, Gisolf J, Richter C, De Boer H. Treatment of calcium and vitamin D deficiency in HIV-positive men on tenofovir-containing antiretroviral therapy. HIV Clin Trials 2012; 13(6): 350-6.
[http://dx.doi.org/10.1310/hct1306-350] [PMID: 23195673]
[62]
Bolland MJ, Grey AB, Horne AM, 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.
[http://dx.doi.org/10.1210/jc.2006-2216] [PMID: 17227801]
[63]
Puthanakit T, Wittawatmongkol O, Poomlek V, et al. Effect of calcium and vitamin D supplementation on bone mineral accrual among HIV-infected Thai adolescents with low bone mineral density. J Virus Erad 2018; 4(1): 6-11.
[PMID: 29568546]
[64]
Nititham S, Srianujata S, Rujirawat T. Dietary intake of phytate, zinc and calcium of self-selected diets of Ubon Ratchathani and Bangkok subjects, Thailand. J Med Assoc Thai 1999; 82(9): 855-61.
[PMID: 10561940]
[65]
Kobayashi MTY, Utsunomiya Y, Sakkayaphan S. Estimation of nutrient intake in Thailand: Influence of differences in food composition tables on estimated intake. J Nutr Med Diet Care 2017; 3: 22.
[http://dx.doi.org/10.23937/2572-3278.1510022]
[66]
Calmy A, Fux CA, Norris R, et al. Low bone mineral density, renal dysfunction, and fracture risk in HIV infection: a cross-sectional study. J Infect Dis 2009; 200(11): 1746-54.
[http://dx.doi.org/10.1086/644785] [PMID: 19874178]
[67]
Hoy J, Grund B, Roediger M, et al. INSIGHT SMART Body Composition Substudy Group. Interruption or deferral of antiretroviral therapy reduces markers of bone turnover compared with continuous therapy: The SMART body composition substudy. J Bone Miner Res 2013; 28(6): 1264-74.
[http://dx.doi.org/10.1002/jbmr.1861] [PMID: 23299909]
[68]
Haskelberg H, Carr A, Emery S. Bone turnover markers in HIV disease. AIDS Rev 2011; 13(4): 240-50.
[PMID: 21975360]
[69]
Allavena C, Delpierre C, Cuzin L, et al. High frequency of vitamin D deficiency in HIV-infected patients: effects of HIV-related factors and antiretroviral drugs. J Antimicrob Chemother 2012; 67(9): 2222-30.
[http://dx.doi.org/10.1093/jac/dks176] [PMID: 22589455]
[70]
Cervero M, Agud JL, García-Lacalle C, 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 Retroviruses 2012; 28(9): 963-71.
[http://dx.doi.org/10.1089/aid.2011.0244] [PMID: 22242918]
[71]
Misiorowski W. A potential influence of vitamin D on HIV infection and bone disease in HIV-positive patients. HIV AIDS Rev 2013; 12: 83-8.
[http://dx.doi.org/10.1016/j.hivar.2013.09.001]
[72]
Masiá M, Padilla S, Robledano C, López N, Ramos JM, Gutiérrez F. Early changes in parathyroid hormone concentrations in HIV-infected patients initiating antiretroviral therapy with tenofovir. AIDS Res Hum Retroviruses 2012; 28(3): 242-6.
[http://dx.doi.org/10.1089/aid.2011.0052] [PMID: 21639815]
[73]
Havens PL, Stephensen CB, Van Loan MD, et al. Adolescent Medicine Trials Network for HIV/AIDS Interventions 117 study team. Decline in bone mass with tenofovir disoproxil fumarate/emtricitabine is associated with hormonal changes in the absence of renal impairment when used by HIV-uninfected adolescent boys and young men for HIV preexposure prophylaxis. Clin Infect Dis 2017; 64(3): 317-25.
[http://dx.doi.org/10.1093/cid/ciw765] [PMID: 28013265]
[74]
Childs KE, Fishman SL, Constable C, et al. Short communication: Inadequate vitamin D exacerbates parathyroid hormone elevations in tenofovir users. AIDS Res Hum Retroviruses 2010; 26(8): 855-9.
[http://dx.doi.org/10.1089/aid.2009.0308] [PMID: 20672993]
[75]
Havens PL, Kiser JJ, Stephensen CB, et al. Adolescent Medicine Trials Network for HIV/AIDS Interventions (ATN) 063 Study Team. Association of higher plasma vitamin D binding protein and lower free calcitriol levels with tenofovir disoproxil fumarate use and plasma and intracellular tenofovir pharmacokinetics: cause of a functional vitamin D deficiency? Antimicrob Agents Chemother 2013; 57(11): 5619-28.
[http://dx.doi.org/10.1128/AAC.01096-13] [PMID: 24002093]


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VOLUME: 18
ISSUE: 1
Year: 2020
Page: [52 - 62]
Pages: 11
DOI: 10.2174/1570162X18666200106150806

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