skip to content

Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection

  •   Table of Contents

Download Guidelines

Management of Medication Toxicity or Intolerance

Osteopenia and Osteoporosis

Last Updated: April 27, 2017; Last Reviewed: April 27, 2017

Table 13j. Antiretroviral Therapy-Associated Adverse Effects and Management Recommendations—Osteopenia and Osteoporosis
Adverse Effects Associated ARVs Onset/Clinical Manifestations Estimated Frequency Risk Factors Prevention/ Monitoring Management
Osteopenia and Osteoporosis Any ART regimen

Specific Agents of Possible Concern:
  • TDF
  • PIs, especially LPV/r
Onset:
  • Any age; decreases in BMD usually see early after initiation of ART.
Presentation:
  • Most commonly asymptomatic
  • Rarely presents as osteoporosis; a clinical diagnosis defined by evidence of bone fragiility (e.g., fracture with minimal trauma).
BMD z Score Less Than -2.0:
  • <10% in U.S. cohorts
  • Approximately 20% to 30% in international cohorts
Longer duration and greater severity of HIV disease

Growth  or pubertal delay

Low BMI

Lipodystrophy

Non-black race

Smoking

Prolonged systemic corticosteroid use

Medroxyprog-esterone use

Limited weight-bearing exercise
Prevention:
  • Ensure sufficient calcium intake and vitamin D sufficiency.
  • Encourage weight-bearing exercise.
  • Minimize modifiable risk factors (e.g., smoking, low BMI, use of steroids or medroxyprog-esterone).
Monitoring:
  • Assess nutritional intake (calcium, vitamin D, and total calories).
  • Consider obtaining serum 25-OH-vitamin D level.a
  • DXA.b
Same options as for prevention.

Consider change in ARV regimen (e.g., changing TDF to TAF).

Role of bisphosphonates not established in children with HIV infection.

a Some experts would periodically measure 25-OH-vitamin D, especially in HIV-infected urban youth, because in that population, the prevalence of vitamin D insufficiency is high.

Until more data are available about the long-term effects of TDF on bone mineral acquisition in childhood, some experts would obtain a DXA at baseline and every 6 to 12 months for prepubertal children and children in early puberty who are initiating treatment with TDF. DXA could also be considered in adolescent women on TDF and medroxyprogesterone and in children with indications not uniquely related to HIV infection (such as cerebral palsy).

Key to Acronyms: ART = antiretroviral therapy; ARV = antiretroviral; BMD = bone mineral density; BMI = body mass index; DXA = dual-energy x-ray absorptiometry; LPV/r = lopinavir/ritonavir; PI = protease inhibitor; TDF = tenofovir disoproxil fumarate, TAF= tenofovir alafenamide

References
Osteopenia and Osteoporosis

  1. Gafni RI, Hazra R, Reynolds JC, et al. Tenofovir disoproxil fumarate and an optimized background regimen of antiretroviral agents as salvage therapy: impact on bone mineral density in HIV-infected children. Pediatrics. 2006;118(3):e711-718. Available at http://www.ncbi.nlm.nih.gov/pubmed/16923923.
  2. Jacobson DL, Lindsey JC, Gordon CM, et al. Total body and spinal bone mineral density across Tanner stage in perinatally HIV-infected and uninfected children and youth in PACTG 1045. AIDS. 2010;24(5):687-696. Available at http://www.ncbi.nlm.nih.gov/pubmed/20168204.
  3. Jacobson DL, Spiegelman D, Duggan C, et al. Predictors of bone mineral density in human immunodeficiency virus-1 infected children. Journal of Pediatric Gastroenterology and Nutrition. 2005;41(3):339-346. Available at http://www.ncbi.nlm.nih.gov/pubmed/16131991.
  4. Kalkwarf HJ, Zemel BS, Gilsanz V, et al. The bone mineral density in childhood study: bone mineral content and density according to age, sex, and race. J Clin Endocrin Metab. 2007;92(6):2087-2099. Available at http://www.ncbi.nlm.nih.gov/pubmed/17311856.
  5. Bachrach LK, Sills IN, Section on E. Clinical report-bone densitometry in children and adolescents. Pediatrics. 2011;127(1):189-194. Available at http://www.ncbi.nlm.nih.gov/pubmed/21187316.
  6. Lima LR, Silva RC, Giuliano Ide C, Sakuno T, Brincas SM, Carvalho AP. Bone mass in children and adolescents infected with human immunodeficiency virus. Jornal de pediatria. 2013;89(1):91-99. Available at http://www.ncbi.nlm.nih.gov/pubmed/23544816.
  7. Puthanakit T, Saksawad R, Bunupuradah T, et al. Prevalence and risk factors of low bone mineral density among perinatally HIV-infected Thai adolescents receiving antiretroviral therapy. J Acquir Immune Defic Syndr. 2012;61(4):477-483. Available at http://www.ncbi.nlm.nih.gov/pubmed/22918157.
  8. Siberry GK, Li H, Jacobson D, Pediatric ACTGCS. Fracture risk by HIV infection status in perinatally HIV-exposed children. AIDS Res Hum Retroviruses. 2012;28(3):247-250. Available at http://www.ncbi.nlm.nih.gov/pubmed/22471877.
  9. DiMeglio LA, Wang J, Siberry GK, et al. Bone mineral density in children and adolescents with perinatal HIV infection. AIDS. 2013;27(2):211-220. Available at http://www.ncbi.nlm.nih.gov/pubmed/23032412.
  10. Bunders MJ, Frinking O, Scherpbier HJ, et al. Bone mineral density increases in HIV-infected children treated with long-term combination antiretroviral therapy. Clin Infect Dis. 2013;56(4):583-586. Available at http://www.ncbi.nlm.nih.gov/pubmed/23097583.
  11. Huang JS, Hughes MD, Riddler SA, Haubrich RH, AIDS Clinical Trials Group AST. Bone mineral density effects of randomized regimen and nucleoside reverse transcriptase inhibitor selection from ACTG A5142. HIV Clin Trials. 2013;14(5):224-234. Available at http://www.ncbi.nlm.nih.gov/pubmed/24144899.
  12. Puthanakit T, Siberry GK. Bone health in children and adolescents with perinatal HIV infection. J Int AIDS Soc. 2013;16:18575. Available at http://www.ncbi.nlm.nih.gov/pubmed/23782476.
  13. Aurpibul L, Cressey TR, Sricharoenchai S, et al. Efficacy, safety and pharmacokinetics of tenofovir disoproxil fumarate in virologic-suppressed HIV-infected children using weight-band dosing. Pediatr Infect Dis J. 2015;34(4):392-397. Available at http://www.ncbi.nlm.nih.gov/pubmed/25760566.
  14. 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):815-824. Available at http://www.ncbi.nlm.nih.gov/pubmed/26075752.
  15. Ross AC. The 2011 report on dietary reference intakes for calcium and vitamin D. Public Health Nutr. 2011;14(5):938-939. Available at http://www.ncbi.nlm.nih.gov/pubmed/21492489.
  16. Mirani G, Williams PL, Chernoff M, et al. Changing trends in complications and mortality rates among US youth and young adults with HIV infection in the Era of Combination Antiretroviral Therapy. Clin Infect Dis. 2015;61(12):1850-1861. Available at http://www.ncbi.nlm.nih.gov/pubmed/26270680.
  17. Eckard AR, Mora S. Bone health in HIV-infected children and adolescents. Curr Opin HIV AIDS. 2016;11(3):294-300. Available at http://www.ncbi.nlm.nih.gov/pubmed/26890208.
  18. Okonkwo RI, Weidmann AE, Effa EE. Renal and bone adverse effects of a tenofovir-based regimen in the treatment of HIV-infected children: a systematic review. Drug Safety. 2016;39(3):209-218. Available at http://www.ncbi.nlm.nih.gov/pubmed/26692394.
  19. Palchetti CZ, Szejnfeld VL, de Menezes Succi RC, et al. Impaired bone mineral accrual in prepubertal HIV-infected children: a cohort study. Braz J Infect Dis. 2015;19(6):623-630. Available at http://www.ncbi.nlm.nih.gov/pubmed/26477385.
  20. Mills A, Arribas JR, Andrade-Villanueva J, et al. Switching from tenofovir disoproxil fumarate to tenofovir alafenamide in antiretroviral regimens for virologically suppressed adults with HIV-1 infection: a randomised, active-controlled, multicentre, open-label, phase 3, non-inferiority study. Lancet Infect Dis. 2016;16(1):43-52. Available at http://www.ncbi.nlm.nih.gov/pubmed/26538525.
  21. Tebas P, Kumar P, Hicks C, et al. Greater change in bone turnover markers for efavirenz/emtricitabine/tenofovir disoproxil fumarate versus dolutegravir + abacavir/lamivudine in antiretroviral therapy-naive adults over 144 weeks. AIDS. 2015;29(18):2459-2464. Available at http://www.ncbi.nlm.nih.gov/pubmed/26355674.
  22. Kizito H, Gaur A, Prasitsuebsai W, et al. Changes in renal laboratory parameters and bone mineral density in treatment-naïve HIV-1-infected adolescents initiating therapy with INSTI-based single-tablet regimens containing tenofovir alafenamide (TAF) or tenofovir disoproxil fumarate (TDF). Presented at: The 21st International AIDS Conference. 2016. Durban, South Africa.

Download Guidelines