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
Last Updated: April 16, 2019; Last Reviewed: April 16, 2019
|Adverse Effects||Associated ARVs||Onset/Clinical Manifestations||Estimated Frequency||Risk Factors||Prevention/ Monitoring||Management|
|Global CNS Depression||LPV/r oral solution (contains both ethanol and propylene glycol as excipients)||Onset:
|Unknown; rare case reports have been published||Prematurity
Low birth weight
Aged <14 days (whether birth was premature or term)
|Avoid use of LPV/r until a postmenstrual age of 42 weeks and a postnatal age of ≥14 days.||Discontinue LPV/r; symptoms should resolve in 1 day–5 days.
If needed, reintroduction of LPV/r can be considered once outside the vulnerable period (i.e., postmenstrual age of 42 weeks and a postnatal age ≥14 days).
|Neuropsychiatric Symptoms and Other CNS Manifestations||EFV||Onset:
|Variable, depending on age, symptoms, and assessment method
|Insomnia is associated with elevated EFV trough concentration (≥4 mcg/mL)
CYP2B6 polymorphisms that decrease EFV metabolism and cause increased EFV serum concentrations (CYP2B6 516 TT genotype or co-carriage of CYP2B6 516 G/T and 983 T/C variants)
Prior history of psychiatric illness or use of psychoactive drugs
|Administer EFV on an empty stomach, preferably at bedtime.
Prescreen for psychiatric illness; avoid use in the presence of psychiatric illness, including depression or suicidal thoughts. Avoid concomitant use of psychoactive drugs.
Consider using TDM in children with mild or moderate EFV-associated toxicities
|If symptoms are excessive or persistent, obtain EFV trough concentration. If EFV trough concentration >4 mcg/mL and/or symptoms are severe, strongly consider drug substitution if a suitable alternative exists.
Alternatively, consider dose reduction with repeat TDM and dose adjustment (with expert pharmacologist input).
||Prior history of neuropsychiatric illness||Monitor carefully for depressive disorders and other CNS symptoms.||Consider drug substitution in cases of severe symptoms.|
||Elevated RAL concentrations
Co-treatment with TDF, a PPI, or inhibitors of UGT1A1
Prior history of insomnia or depression
|Prescreen for psychiatric symptoms.
Monitor carefully for CNS symptoms.
Use with caution in the presence of drugs that increase RAL concentration.
|Consider drug substitution (RAL or coadministered drug) in cases of severe insomnia or other neuropsychiatric symptoms.|
||Pre-existing depression or other psychiatric illness
Higher frequency of neuropsychiatric symptoms reported when coadministered with ABC; however, evidence is conflicting.
UGT1A1*6 and/or *28 polymorphism (reported in patients of Asian descent)
|Use with caution in the presence of psychiatric illness, especially depression.
Consider morning dosing of DTG.
|For persistent or severe neuropsychiatric symptoms, consider discontinuation of DTG if suitable alternative exists.
For mild symptoms, continue DTG and counsel patient that symptoms will likely resolve with time.
|Key to Acronyms: ABC = abacavir; ARV = antiretroviral; CNS = central nervous system; CYP = cytochrome P; DTG = dolutegravir; EEG = electroencephalogram; EFV = efavirenz; INSTI = integrase strand transfer inhibitor; LPV/r = lopinavir/ritonavir; PPI = proton pump inhibitor; RAL = raltegravir; RPV = rilpivirine; TDF = tenofovir disoproxil fumarate; TDM = therapeutic drug monitoring; UGT = uridine diphosphate-glucuronosyltransferase|