Decreased bone mineral density (BMD) has been associated with the use of tenofovir disoproxil fumarate (TDF) in HIV-infected adults. The data in HIV-infected children are conflicting. The aim of this study was to assess the safety of a TDF-containing antiretroviral (ARV) regimen on BMD in paediatric patients. We report the results of a longitudinal 60-month follow-up study.
Methods
A total of 21 vertically HIV-infected Caucasian youths (10 male and 11 female) on ARV treatment containing lamivudine, efavirenz and TDF were enrolled (age range 4.9–17.9 years at baseline). BMD was measured at the lumbar spine and in the whole skeleton by DXA. Bone-specific alkaline phosphatase (BAP) was measured as a bone formation marker and urinary N-telopeptide of type-I collagen (NTx) was measured as a bone resorption index.
Results
Baseline mean (±sd) BMD measurements of HIV-infected patients expressed as z-scores were -0.7 (±0.9) for lumbar spine and -0.13 (±1.0) for the whole skeleton. BMD measurements did not change significantly during the 60-month observation period. Both BAP and NTx concentrations were higher than a reference group of controls at baseline and remained unchanged throughout the study.
Conclusions
Our data indicate that a TDF-containing regimen does not decrease the BMD of HIV-infected youths.
References
1.
Antiretroviral Therapy Cohort Collaboration.Life expectancy of individuals on combination antiretroviral therapy in high-income countries: a collaborative analysis of 14 cohort studies.Lancet2008; 372: 293–299.
2.
ObelN., ThomsenH.F., KronborgG.Ischemic heart disease in HIV-infected and HIV-uninfected individuals: a population-based cohort study.Clin Infect Dis2007; 44: 1625–1631.
3.
KotlerD.P.HIV and antiretroviral therapy: lipid abnormalities and associated cardiovascular risk in HIV-infected patients.J Acquir Immune Defic Syndr2008; 49 Suppl 2: S79–S85.
4.
MallewaJ.E., WilkinsE., VilarJ.HIV-associated lipodystrophy: a review of underlying mechanisms and therapeutic options.J Antimicrob Chemother2008; 62: 648–660.
5.
ViganòA., MoraS.Adverse effects of antiretroviral therapy: focus on bone density.Expert Opin Drug Saf2004; 3: 199–208.
6.
GallantJ.E., StaszewskiS., PozniakA.L.Efficacy and safety of tenofovir DF vs stavudine in combination therapy in antiretroviral-naive patients: a 3-year randomized trial.JAMA2004; 292: 191–201.
7.
JonesS., RestrepoD., KasowitzA.Risk factors for decreased bone density and effects of HIV on bone in the elderly.Osteoporos Int2008; 19: 913–918.
8.
GafniR.I., HazraR., ReynoldsJ.C.Tenofovir disoproxil fumarate and an optimized background regimen of antiretroviral agents as salvage therapy: impact on bone mineral density in HIV-infected children.Pediatrics2006; 118: e711–e718.
9.
PurdyJ.B., GafniR.I., ReynoldsJ.C., ZeichnerS., HazraR.Decreased bone mineral density with off-label use of tenofovir in children and adolescents infected with human immunodeficiency virus.J Pediatr2008; 152: 582–584.
10.
GiacometV., MoraS., MartelliL., MerloM., SciannambloM., ViganòA.. A 12-month treatment with tenofovir does not impair bone mineral accrual in HIV-infected children.J Acquir Immune Defic Syndr2005; 40: 448–450.
11.
GiacometV., BedogniG., ManfrediniV.Renal safety of HAART including tenofovir in vertically HIV-infected youths: a 60-month longitudinal study.17th Conference on Retroviruses and Opportunistic Infections. 16–19 February 2010, San Francisco, CA, USA. Abstract 870.
12.
CacciariE., MilaniS., BalsamoA.A Italian cross-sectional growth charts for height, weight and BMI (2 to 20 yr).J Endocrinol Invest2006; 29: 581–593.
13.
TannerJ.M., WhitehouseR.H.Clinical longitudinal standards for height, weight, height velocity and weight velocity and stages of puberty.Arch Dis Child1976; 51: 170–179.
14.
MoraS., PrinsterC., ProverbioM.C.Urinary markers of bone turnover in healthy children and adolescents: Age–related changes and effect of puberty.Calcif Tissue Int1998; 63: 369–374.
15.
MoraS., CafarelliL., ErbaP.Differential effect of age, gender and puberty on bone formation rate assessed by measurement of bone-specific alkaline phosphatase in healthy children and adolescents.J Bone Miner Metab2009; 27: 721–726.
16.
ZuccottiG., ViganòA., GabianoC.Antiretroviral therapy and bone mineral measurements in HIV-infected youths.Bone2010; 46: 1633–1638.
17.
MoraS., SalaN., BricalliD., ZuinG., ChiumelloG., ViganòA.. Bone mineral loss through increased bone turnover in HIV-infected children treated with highly active antiretroviral therapy.AIDS2001; 15: 1823–1829.
18.
MoraS., ZamproniI., BeccioS., BianchiR., GiacometV., ViganòA.. Longitudinal changes of bone mineral density and metabolism in antiretroviral-treated human immunodeficiency virus-infected children.J Clin Endocrinol Metab2004; 89: 24–28.
19.
MoraS., ZamproniI., CafarelliL.Alterations in circulating osteoimmune factors may be responsible for high bone resorption rate in HIV-infected children and adolescents.AIDS2007; 21: 1129–1135.
