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Updated Pediatric ARV Guidelines

Updates to the Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection were released on Thursday, November 1, 2012. Please send your comments to ContactUs@aidsinfo.nih.gov by November 15, 2012.

Corrections were made to the guideline. For a description of the changes, please see the correction notice.

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Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection

Management of Medication Toxicity or Intolerance

Osteopenia, Osteoporosis, Osteonecrosis

(Last updated:11/1/2012; last reviewed:11/1/2012)

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Table 17j. Antiretroviral Therapy-Associated Adverse Effects and Management Recommendations—Osteopenia, Osteoporosis, Osteonecrosis
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Adverse Effects Associated ARVs Onset/Clinical Manifestations Estimated Frequency Risk Factors Prevention/ Monitoring Management
Osteopenia and osteoporosis cART, especially following initiation of cART, regardless of regimen.

Specific agents of possible concern:
TDF, d4T, and PIs

 Onset:
Any age; greatest risk in months after initiation of associated ARV.

Presentation:
Most commonly asymptomatic; fracture (rare).

Osteoporosis diagnosis in children requires clinical evidence of bone fragility (e.g., fracture with minimal trauma) and cannot rely solely on measured low BMD.

 Low BMD:
20% of children treated with cART had BMD 
z score <-1.5. 		Longer duration of HIV infection

Greater severity of HIV disease

Growth delay, pubertal delay

Low BMI

Lipodystrophy

Non-black race

Smoking

Corticosteroid use

Medroxy-progesterone use

 Prevention:
Ensure sufficient calcium and vitamin D intake.

Encourage weight-bearing exercise.

Minimize modifiable risk factors (smoking, low BMI, steroid use).

Monitoring:
Assess nutritional intake (calcium, vitamin D, and total calories).

Obtain serum 25-OH-vitamin D.a

Obtain DXA.b

 Ensure sufficient calcium and vitamin D intake.

Encourage weight-bearing exercise.

Reduce modifiable risk factors (smoking, low BMI, use of steroids, medroxyprogesterone).

Role of bisphosphonates not established in children.

Consider change in ARV regimen.
Osteonecrosis No specific ARV identified; may be related to HIV infection itself. Onset:
Any age

Presentation:
Limp; hip or other periarticular pain

Asymptomatic reported in adults

 Prevalence:
0.2% in children

Incidence:
0.03% per year in children

 Children:
Unknown

Adults:
Steroid use

Alcohol abuse

Hemo-globinopathies

Hyperlipidemia

Pancreatitis

Osteopenia

Osteoporosis

Hypercoagulable states

Prevention:
Minimize steroid and alcohol use.

Monitoring:
Consider diagnostic evaluation in patients with unexplained limp, hip or other periarticular pain.

 Confirm diagnosis:
Obtain plain radiographs and MRI; bone scan or CT if negative x-ray/MRI but clinical suspicion high.

Treatment:
Early stages:
Decrease weight bearing on affected joint and use analgesic. Limited evidence for use of bisphosphonates.

Later stages:
Consider surgical intervention.

a Some experts would periodically measure 25-OH-vitamin D, especially in HIV-infected urban youth because, in this population, the prevalence of vitamin D insufficiency is high.
b Until more data are available about the long-term effects of tenofovir 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 tenofovir. DXA should also be obtained in children with indications not uniquely related to HIV infection (such as cerebral palsy).

Key to Acronyms: ARVs = antiretrovirals, BMD = bone mineral density, BMI = body mass index, cART = combination antiretroviral therapy, CT = computed tomography, d4T = stavudine, DXA = dual energy x-ray absorptiometry, MRI = magnetic resonance imaging, PIs = protease inhibitors, TDF = tenofovir disoproxil fumarate

References

Osteopenia and Osteoporosis

  1. McComsey GA, Tebas P, Shane E, et al. Bone disease in HIV infection: a practical review and recommendations for HIV care providers. Clin Infect Dis. Oct 15 2010;51(8):937-946. Available at http://www.ncbi.nlm.nih.gov/pubmed/20839968.
  2. Mora S, Sala N, Bricalli D, et al. Bone mineral loss through increased bone turnover in HIV-infected children treated with highly active antiretroviral therapy. AIDS. 2001;15(14):1823-1829. Available at http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11579244.
  3. Mora S, Zamproni I, Beccio S, Bianchi R, Giacomet V, Vigano A. Longitudinal changes of bone mineral density and metabolism in antiretroviral-treated human immunodeficiency virus-infected children. J Clin Endocr Metab Jan 2004;89(1):24-28. Available at http://www.ncbi.nlm.nih.gov/pubmed/14715822.
  4. Hazra R, Gafni RI, Maldarelli F, et al. Tenofovir disoproxil fumarate and an optimized background regimen of antiretroviral agents as salvage therapy for pediatric HIV infection. Pediatrics. Dec 2005;116(6):e846-854. Available at http://www.ncbi.nlm.nih.gov/pubmed/16291735.
  5. 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. Sep 2006;118(3):e711-718. Available at http://www.ncbi.nlm.nih.gov/pubmed/16923923.
  6. Purdy JB, Gafni RI, Reynolds JC, Zeichner S, Hazra R. Decreased bone mineral density with off-label use of tenofovir in children and adolescents infected with human immunodeficiency virus. J Pediatr. Apr 2008;152(4):582-584. Available at http://www.ncbi.nlm.nih.gov/pubmed/18346519.
  7. 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. Mar 13 2010;24(5):687-696. Available at http://www.ncbi.nlm.nih.gov/pubmed/20168204.
  8. Jacobson DL, Spiegelman D, Duggan C, et al. Predictors of bone mineral density in human immunodeficiency virus-1 infected children. J Pediatr Gastr Nutr. Sep 2005;41(3):339-346. Available at http://www.ncbi.nlm.nih.gov/pubmed/16131991.
  9. 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 Endocr Metab. Jun 2007;92(6):2087-2099. Available at http://www.ncbi.nlm.nih.gov/pubmed/17311856.
  10. Bachrach LK, Sills IN, Section on E. Clinical report-bone densitometry in children and adolescents. Pediatrics. Jan 2011;127(1):189-194. Available at http://www.ncbi.nlm.nih.gov/pubmed/21187316.

Osteonecrosis

  1. Gaughan DM, Mofenson LM, Hughes MD, et al. Osteonecrosis of the hip (Legg-Calve-Perthes disease) in human immunodeficiency virus-infected children. Pediatrics. May 2002;109(5):E74-74. Available at http://www.ncbi.nlm.nih.gov/pubmed/11986480.
  2. Glesby MJ. Bone disorders in human immunodeficiency virus infection. Clin Infect Dis. 2003;37 Suppl 2(Suppl 2):S91-95. Available at http://www.ncbi.nlm.nih.gov/pubmed/12942380.
  3. Morse CG, Mican JM, Jones EC, et al. The incidence and natural history of osteonecrosis in HIV-infected adults. Clin Infect Dis. Mar 1 2007;44(5):739-748. Available at http://www.ncbi.nlm.nih.gov/pubmed/17278070.
  4. Allison GT, Bostrom MP, Glesby MJ. Osteonecrosis in HIV disease: epidemiology, etiologies, and clinical management. AIDS. Jan 3 2003;17(1):1-9. Available at http://www.ncbi.nlm.nih.gov/pubmed/12478064.