Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection

The information in the brief version is excerpted directly from the full-text guidelines. The brief version is a compilation of the tables and boxed recommendations.

  •   Table of Contents

Download Guidelines

Management of Medication Toxicity or Intolerance

Osteopenia and Osteoporosis

Last Updated: April 14, 2020; Last Reviewed: April 14, 2020


  1. Arpadi SM, Shiau S, Strehlau R, et al. Efavirenz is associated with higher bone mass in South African children with HIV. AIDS. 2016;30(16):2459-2467. Available at:
  2. 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:
  3. Bachrach LK, Gordon CM, Section On E. Bone densitometry in children and adolescents. Pediatrics. 2016;138(4). Available at:
  4. 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:
  5. 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:
  6. Eckard AR, Mora S. Bone health in HIV-infected children and adolescents. Curr Opin HIV AIDS. 2016;11(3):294-300. Available at:
  7. Eckard AR, O'Riordan MA, Rosebush JC, 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):539-546. Available at:
  8. 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:
  9. Havens PL, Stephensen CB, Van Loan MD, 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):220-228. Available at:
  10. Huang JS, Hughes MD, Riddler SA, Haubrich RH, AIDS Clinical Trials Group A. Study Team. 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:
  11. 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 Endocrinol Metab. 2007;92(6):2087-2099. Available at:
  12. LaFleur J, Bress AP, Myers J, et al. Tenofovir-associated bone adverse outcomes among a US national historical cohort of HIV-infected veterans: risk modification by concomitant antiretrovirals. Infect Dis Ther. 2018;7(2):293-308. Available at:
  13. 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:
  14. 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:
  15. 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 Saf. 2016;39(3):209-218. Available at:
  16. 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:
  17. 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:
  18. 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:
  19. Puthanakit T, Siberry GK. Bone health in children and adolescents with perinatal HIV infection. J Int AIDS Soc. 2013;16:18575. Available at:
  20. 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. Available at:
  21. Siberry GK, Li H, Jacobson D, Pediatric AIDS Clinical Trials Group C. Study. Fracture risk by HIV infection status in perinatally HIV-exposed children. AIDS Res Hum Retroviruses. 2012;28(3):247-250. Available at:
  22. 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:
  23. Schall JI, Hediger ML, Zemel BS, Rutstein RM, Stallings VA. Comprehensive safety monitoring of 12-month daily 7000-IU vitamin D3 supplementation in human immunodeficiency virus-infected children and young adults. JPEN J Parenter Enteral Nutr. 2016;40(7):1057-1063. Available at:
  24. Dougherty KA, Schall JI, Zemel BS, et al. Safety and efficacy of high-dose daily vitamin D3 supplementation in children and young adults infected with human immunodeficiency virus. J Pediatric Infect Dis Soc. 2014;3(4):294-303. Available at:
  25. Negredo E, Langohr K, Bonjoch A, et al. High risk and probability of progression to osteoporosis at 10 years in HIV-infected individuals: the role of PIs. J Antimicrob Chemother. 2018;73(9):2452-2459. Available at:
  26. Havens PL, Long D, Schuster GU, et al. Tenofovir disoproxil fumarate appears to disrupt the relationship of vitamin D and parathyroid hormone. Antivir Ther. 2018;23(7):623-628. Available at:
  27. Van Welzen BJ, Thielen MAJ, Mudrikova T, Arends JE, Hoepelman AIM. Switching tenofovir disoproxil fumarate to tenofovir alafenamide results in a significant decline in parathyroid hormone levels: uncovering the mechanism of tenofovir disoproxil fumarate-related bone loss? AIDS. 2019;33(9):1531-1534. Available at:
  28. Penner J, Ferrand RA, Richards C, Ward KA, Burns JE, Gregson CL. The impact of vitamin D supplementation on musculoskeletal health outcomes in children, adolescents, and young adults living with HIV: A systematic review. PLoS One. 2018;13(11):e0207022. Available at:
  29. Holick MF, Binkley NC, Bischoff-Ferrari HA, et al. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2011;96(7):1911-1930. Available at:
  30. Ross AC, Manson JE, Abrams SA, et al. The 2011 report on dietary reference intakes for calcium and vitamin D from the Institute of Medicine: what clinicians need to know. J Clin Endocrinol Metab. 2011;96(1):53-58. Available at:
  31. Burt LA, Billington EO, Rose MS, Raymond DA, Hanley DA, Boyd SK. Effect of high-dose vitamin D supplementation on volumetric bone density and bone strength: a randomized clinical trial. JAMA. 2019;322(8):736-745. Available at:

Download Guidelines