Table 17k. Antiretroviral Therapy-Associated Adverse Effects and Management Recommendations—Peripheral Nervous System Toxicity Adverse Effects
Associated ARVs
ARV toxic d4T, ddI neuropathy*
Onset/Clinical Manifestations Onset: Variable, weeks to months following NRTI initiation
Presentation: Pain described as aching, burning, painful numbness
Estimated Frequency
Risk Factors
Perinatal HIV in HIV-infected fection: adults: Prevalence: 1.13% (2001 baseline PACTG 219C)
Prevention/ Monitoring
• Limit use of d4T • Discontinue offending and ddI if possible. agent.
• Pre-existing neu • As part of routine care, monitor for ropathy (dia symptoms and betes, alcohol signs of peripheral abuse, vitamin neuropathy. B12 deficiency)
Incidence: 0.9%; 0.23 per 100 per • Elevated triglyc pain distribution bilat son-years (2001– eride levels eral soles of feet, as 2006) • Older age 0.1% incidence cending to legs and • Poor nutrition with use of fingertips; d4T+3TC+NVP • More advanced hyperalgesia (lowered over mean follow- HIV disease pain threshold) up of 1.3 years • Mitochondrial allodynia (non-noxius HIV-infected DNA haplogroup stimuli cause pain) decreased or absent ankle reflexes
Management
• Persistent pain can be difficult to treat; topical capsaicin 8% may be helpful. • There are insufficient data to allow the Panel to safely recommend the use of any of the following modalities in children: tricyclic anti depressants, gabapentin, prega balin, mexilitine, or lamotrigine.
adults:
31% taking d4T
* HIV infection itself may cause a distal sensory neuropathy that is phenotypically identical to ARV toxic neuropathy.
Key to Acronyms: 3TC = lamivudine; ARV = antiretroviral; d4T = stavudine; ddI = didanosine; NRTI = nucleoside reverse transcriptase inhibitor; NVP = nevirapine
References 1. Nachman SA, Chernoff M, et al. Incidence of noninfectious conditions in perinatally HIV-infected children and adoles cents in the HAART era. Arch Pediatr Adolesc Med. 2009;163(2):164-171. 2. Kabue MM, Buck WC, Kazembe PN, Kline MW. Discontinuation of standard first-line antiretroviral therapy in a cohort of 1434 Malawian children. 5th IAS Conference on HIV Pathogenesis and Treatment. 2009. Abstract WEPED175. 3. Van Dyke RB, Wang L, et al. Toxicities associated with dual nucleoside reverse-transcriptase inhibitor regimens in HIVinfected children. J Infect Dis. 2008;198(11):1599-1608. 4. Keswani SC, Pardo CA, Cherry CL, et al. HIV-associated sensory neuropathies. AIDS. 2002;16(16):2105-2117. 5. Ances BM, Vaida F, et al. Role of metabolic syndrome components in HIV-associated sensory neuropathy. AIDS. 2009;23(17):2317-2322. 6. Banerjee S, McCutchan JA, et al. Hypertriglyceridemia in combination antiretroviral-treated HIV-positive individuals: potential impact on HIV sensory polyneuropathy. AIDS. 2011;25(2):F1-6. 7. Canter JA, Robbins GK, et al. African mitochondrial DNA subhaplogroups and peripheral neuropathy during antiretrovi ral therapy. J Infect Dis. 2010;201(11):1703-1707. 8. McCormack PL. Capsaicin dermal patch: in non-diabetic peripheral neuropathic pain. Drugs. 2010;70(14):1831-1842. 9. Phillips TJ, Cherry CL, et al. Pharmacological treatment of painful HIV-associated sensory neuropathy: a systematic re view and meta-analysis of randomized controlled trials. PLoS One. 2010;5(12):e14433.
Guidelines for the Use of Antiretroviral Agents in Pediatric Infection
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