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 14, 2020; Last Reviewed: April 14, 2020
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: AE = adverse effects; ART = antiretroviral therapy; CD4 = CD4 T lymphocyte; HCV = hepatitis C virus; IRIS = immune reconstitution inflammatory syndrome; TB = tuberculosis; TMP-SMX = trimethoprim-sulfamethoxazole; ZDV = zidovudine|
Table 18. Options for Regimens with at Least Two Fully Active Agents to Achieve Virologic Suppression in Patients with Virologic Failure and Evidence of Viral Resistance
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 when 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. 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.
|Prior Regimen||New Regimen Optionsa|
|Two NRTIs plus an NNRTI||Two NRTIs plus a boosted PI
Two NRTIs plus an INSTIb
|Two NRTIs plus a PI||Two NRTIs plus an INSTI
Two NRTIs plus a different boosted PI
INSTI plus a different boosted PI with or without an NNRTI and with or without NRTI(s)
|Two NRTIs plus an INSTI||Two NRTIs plus a boosted PI
DTGa,b or BICb (if not used in the prior regimen) with a boosted PI with or without 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)||If NRTIs Are Fully Active:
|a Exposure to DTG around the time of conception has been associated with a small but significant increase in the risk of infant NTDs. Additional information and specific recommendations about the use of DTG in women and adolescents of childbearing potential and in those who are pregnant or who are trying to conceive 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, Recommendations for Use of Antiretroviral Drugs During Pregnancy, and Appendix D. Dolutegravir Counseling Guide for Health Care Providers).
b RAL has a low barrier to resistance and requires twice-daily dosing in children and adolescents; BIC and DTG have a higher barrier to resistance and only require once-daily dosing.
Key: 3TC = lamivudine; ART = antiretroviral therapy; ARV = antiretroviral; BIC = bictegravir; 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; NTD = neural tube defect; PI = protease inhibitor; RAL = raltegravir; RPV = rilpivirine; RTV = ritonavir; T-20 = enfuvirtide; TAF = tenofovir alafenamide; TDF = tenofovir disoproxil fumarate; ZDV = zidovudine