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 Children Receiving Antiretroviral Therapy
Recognizing and Managing Antiretroviral Treatment Failure
Last Updated: April 16, 2019; Last Reviewed: April 16, 2019
Rating of Recommendations: A = Strong; B = Moderate; C = Optional
Rating of Evidence: I = One or more randomized trials in children† with clinical outcomes and/or validated endpoints; I* = One or more randomized trials in adults with clinical outcomes and/or validated laboratory endpoints with accompanying data in children† from one or more well-designed, nonrandomized trials or observational cohort studies with long-term clinical outcomes; II = One or more well-designed, nonrandomized trials or observational cohort studies in children† with long-term outcomes; II* = One or more well-designed, nonrandomized trials or observational studies in adults with long-term clinical outcomes with accompanying data in children† from one or more similar nonrandomized trials or cohort studies with clinical outcome data; III = Expert opinion
† Studies that include children or children/adolescents, but not studies limited to post-pubertal adolescents
|Differential Diagnosis of Poor Immunologic Response Despite Virologic Suppression|
|Poor Immunologic Response Despite Virologic Suppression and Good Clinical Response:
|Differential Diagnosis of Poor Clinical Response Despite Adequate Virologic and Immunologic Responses|
|Key to Acronyms: ART = antiretroviral therapy; CD4 = CD4 T lymphocyte; HCV = hepatitis C virus; IRIS = immune reconstitution inflammatory syndrome; TB = tuberculosis; ZDV = zidovudine|
|Prior Regimen||New Regimen Optionsa|
|Two NRTIs plus NNRTI||
Two NRTIs plus PI
Two NRTIs plus INSTI
|Two NRTIs plus PI||
Two NRTIs plus INSTI
Two NRTIs plus a different RTV-boosted PI
INSTI plus different RTV-boosted PI plus or minus an NNRTI and plus or minus NRTI(s)
|Two NRTIs plus INSTI||
Two NRTIs plus RTV-boosted PI
DTGb (if not used in the prior regimen) plus RTV-boosted PI plus or minus one or two NRTIs. DTG must be given twice daily if a patient has certain documented INSTI mutations, or if there is concern about certain mutations (see the dolutegravir section).
|Failed Regimen(s) That Included NRTI(s), NNRTI(s), and PI(s)||
INSTI plus two NRTIs (if NRTIs are fully active)
INSTI plus two NRTIs plus or minus RTV-boosted PI (if NRTIs are not fully active)
INSTI plus or minus RTV-boosted PI plus or minus (ETR or RPV) plus or minus NRTI(s) (if minimal NRTI activity). Consider adding T-20 and/or MVC if additional active drug(s) are needed.
|a Clinicians should evaluate a patient’s treatment history and drug-resistance test results when choosing an ART regimen in order to optimize ARV drug effectiveness. This is particularly important in selecting the NRTI components of an NNRTI-based regimen, where drug resistance to the NNRTI can occur rapidly if the virus is not sufficiently sensitive to the NRTIs. Regimens should contain at least two, but preferably three, fully active drugs for durable and potent virologic suppression. If the M184V/I mutation associated with FTC and 3TC is present, these medications should be continued if the new regimen contains TDF, TAF, or ZDV as the presence of this mutation may increase susceptibility to these NRTIs. Please see individual drug profiles for information about age limitations (e.g., do not use DRV in children aged <3 years), drug interactions, and dose adjustments when devising a regimen for children with multiclass drug resistance. Collaboration with a pediatric HIV specialist is especially important when choosing regimens for children with multiclass drug resistance. Regimens in this table are provided as examples, but the list is not exhaustive.
b Because of recent concerns about the potential for neural tube defects in infants born to women who conceived while taking regimens that contained dolutegravir, this drug should be prescribed with caution in female adolescents. Specific recommendations about the initiation and use of dolutegravir in women of childbearing potential and in pregnant women are available in the Adult and Adolescent Antiretroviral Guidelines (see Adolescents and Young Adults with HIV and Management of the Treatment-Experienced Patient) and in the Perinatal Guidelines (see Teratogenicity and Recommendations for Use of Antiretroviral Drugs During Pregnancy).
Key to Acronyms: 3TC = lamivudine; ART = antiretroviral therapy; ARV = antiretroviral; DRV = darunavir; DTG = dolutegravir; ETR = etravirine; FTC = emtricitabine; INSTI = integrase strand transfer inhibitor; MVC = maraviroc; NNRTI = non-nucleoside reverse transcriptase inhibitor; NRTI = nucleoside reverse transcriptase inhibitor; PI = protease inhibitor; RPV = rilpivirine; RTV = ritonavir; T-20 = enfuvirtide; TAF = tenofovir alafenamide; TDF = tenofovir disoproxil fumarate; ZDV = zidovudine