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.
Management of Medication Toxicity or Intolerance
Rash and Hypersensitivity Reactions
Last Updated: April 16, 2019; Last Reviewed: April 16, 2019
|Adverse Effects||Associated ARVs||Onset/Clinical Manifestations||Estimated Frequency||Risk Factors||Prevention/Monitoring||Management|
|Rash||Any ARV drug can cause rash||Onset:
Note: A rash can be the initial manifestation of systemic hypersensitivity (see the SJS/TEN/EM Major and HSR sections below).
||Sulfonamide allergy is a risk factor for rash in patients who are taking PIs that contain a sulfonamide moiety (e.g., DRV).
Polymorphisms in CYP2B6 and multiple HLA loci may confer an increased risk of rash in patients who are taking NVP.
|When Starting NVP or Restarting After Interruptions of >14 Days:
||Mild-to-Moderate Maculopapular Rash Without Systemic or Mucosal Involvement:
SJS/ TEN/ EM Major
|Many ARV drugs, especially NNRTIs (see the Estimated Frequency column)||Onset:
||When Starting NVP or Restarting After Interruptions of >14 Days:
||Discontinue all ARV drugs and other possible causative agents (e.g., TMP-SMX).
Provide intensive supportive including care, IV hydration, aggressive wound care, eye care, labial adhesion preventative care, pain management, and antipyretics. Parenteral nutrition and antibiotics may also be necessary.
Corticosteroids and/or IVIG are sometimes used, but the use of these interventions is controversial.
Do not reintroduce the offending medication.
When SJS/TEN/EM major occurs with the use of one NNRTI, many experts would avoid the use of other NNRTIs.
|DRESS||DRV, DTG, EFV, ETR, NVP, RAL, RPV||Onset:
||Rare||Unknown||Obtain a CBC and AST, ALT, and creatinine levels from a patient who presents with suggestive symptoms.||
Discontinue all ARV drugs and other possible causative agents (e.g., TMP-SMX).
The role of systemic steroids in treatment unclear; consultation with a specialist is recommended.
With or without skin involvement and excluding SJS/TEN
With First Use:
|<1% to 9% (varies by ethnicity)||HLA-B*5701 (HSR is very uncommon in people who are HLA-B*5701 negative).
The risk of HSR is higher in patients who are white compared to patients who are black or East Asian.
|Screen for HLA-B*5701. ABC should not be prescribed if HLA-B*5701 is present. The medical record should clearly indicate that ABC is contraindicated.
When starting ABC, counsel patients and families about the signs and symptoms of HSR to ensure prompt reporting of reactions.
|Discontinue ARV drugs and investigate other causes of the symptoms (e.g., a concurrent viral illness).
Provide symptomatic treatment.
Most symptoms resolve within 48 hours after discontinuing ABC.
Do not rechallenge with ABC even if the patient is HLA-B*5701 negative.
||Occurs in 4% of patients on average, with a range of 2.5% to 11%||Adults:
||When Starting NVP or Restarting After Interruptions of >14 Days:
||Discontinue ARV drugs.
Consider other causes for hepatitis and discontinue all hepatotoxic medications. Provide supportive care as indicated and monitor the patient closely.
Do not re-introduce NVP. The safety of other NNRTIs is unknown following symptomatic hepatitis due to NVP, and many experts would avoid the NNRTI drug class when restarting treatment.
||Rare||Unknown||Evaluate for hypersensitivity if the patient is symptomatic.||Discontinue ARV drugs.
Rechallenge with ETR is not recommended.
|MVC||Rash preceding hepatotoxicity||Rare||Unknown||Obtain AST and ALT levels in patients with rash or other symptoms of hypersensitivity.||Discontinue all ARV drugs.
Rechallenge with MVC is not recommended.
|DTG||Rash with hepatic dysfunction||Rare||Unknown||Obtain AST and ALT levels in patients with rash or other symptoms of hypersensitivity.||Discontinue all ARV drugs.
Rechallenge with DTG is contraindicated.
|a The prescribing information for NVP states that patients who experience rash during the 14-day lead-in period should not have the NVP dose increased until the rash has resolved. However, prolonging the lead-in phase beyond 14 days may increase the risk of NVP resistance because of subtherapeutic drug levels. Children who have persistent mild or moderate rash after the lead-in period should receive individualized care. Consult an expert in HIV care when managing these patients. NVP should be stopped and not restarted if the rash is severe or progressing. See the NVP section of the Drug Appendix.
b Lead-in dosing is not recommended when using nevirapine for either empiric or definitive HIV therapy in newborns with perinatal HIV exposure or perinatal HIV. See the NVP section of the Drug Appendix and Table 12.
Key to Acronyms: ABC = abacavir; ALT = alanine transaminase; ARV = antiretroviral; AST = aspartate aminotransferase; ATV = atazanavir; CBC = complete blood count; CD4 = CD4 T lymphocyte; CYP 450 = cytochrome P; DRESS = drug reaction (or rash) with eosinophilia and systemic symptoms; DRV = darunavir; DTG = dolutegravir; EFV = efavirenz; EM = erythema multiforme; ETR = etravirine; FTC = emtricitabine; HLA = human leukocyte antigen; HSR = hypersensitivity reaction; IV = intravenous; IVIG = intravenous immune globulin; LPV/r = lopinavir/ritonavir; MVC = maraviroc; NNRTI = non-nucleoside reverse transcriptase inhibitor; NVP = nevirapine; PEP = post-exposure prophylaxis; PI = protease inhibitor; RAL = raltegravir; RPV = rilpivirine; SJS = Stevens-Johnson syndrome; TDF = tenofovir disoproxil fumarate; TEN = toxic epidermal necrolysis; TMP-SMX = trimethoprim-sulfamethoxazole; ZDV = zidovudine
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