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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

Peripheral Nervous System Toxicity

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

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Table 17k. Antiretroviral Therapy-Associated Adverse Effects and Management Recommendations—Peripheral Nervous System Toxicity
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Adverse Effects Associated ARVs Onset/Clinical Manifestations Estimated Frequencya Risk Factors Prevention/ Monitoring Management
ARV toxic neuropathyb d4T, ddI Onset:
Variable, weeks to months following NRTI initiation

Presentation:
Decreased sensation

Aching, burning, painful numbness

Hyperalgesia (lowered pain threshold)

Allodynia (non-noxious stimuli cause pain)

Decreased or absent ankle reflexes

Distribution: bilateral soles of feet, ascending to legs and fingertips

 HIV-infected children:
1.13% prevalence (baseline 2001); 0.23 per 100 person-years (2001–2006)

0.07%–0.26% incidence in two large African cohorts (aged 1 month–18 years, median follow-up 1.8–3.2 years)

HIV-infected adults:
17%–57% taking d4T

 HIV-infected adults:
Pre-existing neuropathy (diabetes, alcohol abuse, vitamin B12 deficiency)

Elevated triglyceride levels

Older age

Poor nutrition

More advanced HIV disease

Mitochondrial DNA haplogroup

 Limit use of d4T and ddI, if possible.

As part of routine care, monitor for symptoms and signs of peripheral neuropathy.

 Discontinue offending agent.

Persistent pain can be difficult to treat; topical capsaicin 8% may be helpful. Data are insufficient to allow the Panel to safely recommend use of any of the following modalities in children: tricyclic antidepressants, gabapentin, pregabalin, mexilitine, or lamotrigine.

a Peripheral neuropathy may be underreported in children because symptoms are difficult to evaluate in young children.
b HIV infection itself may cause a distal sensory neuropathy that is phenotypically identical to ARV toxic neuropathy.

Key to Acronyms: ARV = antiretroviral, d4T = stavudine, ddI = didanosine, NRTI = nucleoside reverse transcriptase inhibitor

References

  1. Nachman SA, Chernoff M, Gona P, et al. Incidence of noninfectious conditions in perinatally HIV-infected children and adolescents in the HAART era. Arch Pediatr Adolesc Med. Feb 2009;163(2):164-171. Available at http://www.ncbi.nlm.nih.gov/pubmed/19188649.
  2. Buck WC, Kabue MM, Kazembe PN, Kline MW. Discontinuation of standard first-line antiretroviral therapy in a cohort of 1434 Malawian children. J Int AIDS Soc. 2010;13:31. Available at http://www.ncbi.nlm.nih.gov/pubmed/20691049.
  3. Keswani SC, Pardo CA, Cherry CL, Hoke A, McArthur JC. HIV-associated sensory neuropathies. AIDS. Nov 8 2002;16(16):2105-2117. Available at http://www.ncbi.nlm.nih.gov/pubmed/12409731.
  4. Ances BM, Vaida F, Rosario D, et al. Role of metabolic syndrome components in HIV-associated sensory neuropathy. AIDS. Nov 13 2009;23(17):2317-2322. Available at http://www.ncbi.nlm.nih.gov/pubmed/19823068.
  5. Banerjee S, McCutchan JA, Ances BM, et al. Hypertriglyceridemia in combination antiretroviral-treated HIV-positive individuals: potential impact on HIV sensory polyneuropathy. AIDS. Jan 14 2011;25(2):F1-6. Available at http://www.ncbi.nlm.nih.gov/pubmed/21150557.
  6. Canter JA, Robbins GK, Selph D, et al. African mitochondrial DNA subhaplogroups and peripheral neuropathy during antiretroviral therapy. J Infect Dis. Jun 1 2010;201(11):1703-1707. Available at http://www.ncbi.nlm.nih.gov/pubmed/20402593.
  7. McCormack PL. Capsaicin dermal patch: in non-diabetic peripheral neuropathic pain. Drugs. Oct 1 2010;70(14):1831-1842. Available at http://www.ncbi.nlm.nih.gov/pubmed/20836576.
  8. Phillips TJ, Cherry CL, Cox S, Marshall SJ, Rice AS. Pharmacological treatment of painful HIV-associated sensory neuropathy: a systematic review and meta-analysis of randomised controlled trials. PLoS One. 2010;5(12):e14433. Available at http://www.ncbi.nlm.nih.gov/pubmed/21203440.
  9. Menezes CN, Maskew M, Sanne I, Crowther NJ, Raal FJ. A longitudinal study of stavudine-associated toxicities in a large cohort of South African HIV infected subjects. BMC Infect Dis. 2011;11:244. Available at http://www.ncbi.nlm.nih.gov/pubmed/21923929.
  10. Wadley AL, Cherry CL, Price P, Kamerman PR. HIV neuropathy risk factors and symptom characterization in stavudine-exposed South Africans. Journal of Pain and Symptom Management. Apr 2011;41(4):700-706. Available at http://www.ncbi.nlm.nih.gov/pubmed/21145196.
  11. Tukei VJ, Asiimwe A, Maganda A, et al. Safety and tolerability of antiretroviral therapy among HIV-infected children and adolescents in Uganda. J Acquir Immune Defic Syndr. Mar 1 2012;59(3):274-280. Available at http://www.ncbi.nlm.nih.gov/pubmed/22126740.