Sage Journals: Discover world-class research

Abstract

Hyperparathyroidism has been described in people living with HIV undergoing tenofovir disoproxil fumarate (TDF)-containing antiretroviral therapy (ART), but differences in calcium levels have never been investigated in detail. We aimed to compare the prevalence of hypocalcemia between patients with and without TDF-containing ART. The patients and methods were a retrospective cohort study in HIV-infected adult patients receiving dolutegravir and either abacavir (ABC)/lamivudine (3TC) or TDF/emtricitabine in a single center in Munich, Germany. Of 172 patients, 126 (73.3%) were male and the median age was 48.5 years (interquartile range 42–54). Average calcium levels were 2.24 (2.21–2.29) mmol/l and 2.21 (2.16–2.26) mmol/l (P < 0.001) with a prevalence of at least one episode of total calcium <2.12 mmol/l of 16.2 and 34.4% in the groups treated with ABC/3TC and TDF/emtricitabine, respectively (P = 0.006). TDF use was independently associated with the occurrence of albumin-corrected calcium levels of <2.12 mmol/l (odds ratio: 6.7 [1.3–35.6]; P = 0.025). Hypocalcemia seems to occur more often in TDF-treated patients. Further research into hypocalcemia with TDF and potential cardiovascular effects may be of benefit based on these findings.

Keywords

Calcium tenofovir secondary hyperparathyroidism,HIV

Get full access to this article

View all access options for this article.

References

Grant

Cotter

AG.

Tenofovir and bone health. Curr Opin HIV AIDS 2016; 11: 326–332.

Patricio

Jr Lopes

Medeiros

et al . Tenofovir monotherapy for hepatitis B after 1 year does not produce renal dysfunction, but is associated with hyperparathyroidism not related to vitamin D. Eur J Gastroenterol Hepatol 2016; 28: 64–69.

Rosenvinge

Gedela

Copas

et al . Tenofovir-linked hyperparathyroidism is independently associated with the presence of vitamin D deficiency. J Acquir Immune Defic Syndr 2010; 54: 496–499.

Samarawickrama

Jose

Sabin

et al . No association between vitamin D deficiency and parathyroid hormone, bone density and bone turnover in a large cohort of HIV-infected men on tenofovir. J Int AIDS Soc 2014; 17: 19568.

Das

Bopitya

Taha

et al . Relationship between vitamin D, parathyroid hormone, bone mineral density, fracture and antiretroviral therapy in HIV patients. Recent Pat Antiinfect Drug Discov 2014; 9: 6–13.

Conigrave

AD.

The calcium-sensing receptor and the parathyroid: past, present, future. Front Physiol 2016; 7: 563.

Girgis

Wong

Ngu

et al . Hypophosphataemic osteomalacia in patients on adefovir dipivoxil. J Clin Gastroenterol 2011; 45: 468–473.

Lin

Zhuo

Zhang

Nephrolithiasis and osteomalacia associated with adefovir-induced Fanconi syndrome in a patient with hepatitis B. BMC Nephrol 2017; 18: 275.

Earle

Seneviratne

Shaker

et al . Fanconi’s syndrome in HIV+ adults: report of three cases and literature review. J Bone Miner Res 2004; 19: 714–721.

10.

Norlin

Lundqvist

Ellfolk

et al . Drug-mediated gene regulation of vitamin D3 metabolism in primary human dermal fibroblasts. Basic Clin Pharmacol Toxicol 2017; 120: 59–63.

11.

Brown

McComsey

GA.

Association between initiation of antiretroviral therapy with efavirenz and decreases in 25-hydroxyvitamin D. Antivir Ther 2010; 15: 425–429.

12.

Welz

Childs

Ibrahim

et al . Efavirenz is associated with severe vitamin D deficiency and increased alkaline phosphatase. AIDS 2010; 24: 1923–1928.

13.

Welz

Childs

Post

FA.

Do nevirapine and efavirenz affect vitamin D homeostasis similarly?

AIDS 2011; 25: 875–876.

14.

Dao

Patel

Overton

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: 396–405.

15.

Bursac

Gauss

Williams

et al . Purposeful selection of variables in logistic regression. Source Code Biol Med 2008; 3: 17.

16.

Mingione

Maruca

Chiappori

et al . High parathyroid hormone concentration in tenofovir-treated patients are due to inhibition of calcium-sensing receptor activity. Biomed Pharmacother 2017; 97: 969–974.

17.

Noe

Heldwein

Wiese

et al . Secondary hyperparathyroidism in HIV infected patients. Central Europe Horm Metab Res 2018; 50(4): 317–324.

18.

Pocaterra

Carenzi

Ricci

et al . Secondary hyperparathyroidism in HIV patients: is there any responsibility of highly active antiretroviral therapy? AIDS 2011; 25: 1430–1433.

19.

Masia

Padilla

Robledano

et al . Early changes in parathyroid hormone concentrations in HIV-infected patients initiating antiretroviral therapy with tenofovir. AIDS Res Hum Retroviruses 2012; 28: 242–246.

20.

Mace

Gravesen

Nordholm

et al. Fibroblast growth factor (FGF) 23 regulates the plasma levels of parathyroid hormone in vivo through the FGF receptor in normocalcemia, but not in hypocalcemia. Calcif Tissue Int 2018; 102(1): 85–92.

21.

David

Dai

Martin

et al . Calcium regulates FGF-23 expression in bone. Endocrinology 2013; 154: 4469–4482.

22.

Grigsby

Pham

Gopalakrishnan

et al . Downregulation of Gnas, Got2 and Snord32a following tenofovir exposure of primary osteoclasts. Biochem Biophys Res Commun 2010; 391: 1324–1329.

23.

Chen

Scherzer

Hsue

et al.

Association of tenofovir use with risk of incident heart failure in HIV-infected patients. J Am Heart Assoc 2017; 6(4): pii: e005387.

Tenofovir disoproxil fumarate/emtricitabine is associated with a higher risk of hypocalcemia compared to abacavir/lamivudine – results from a German cohort study

Abstract

Keywords

Get full access to this article

References