(Last updated: March 1, 2016; last reviewed: March 1, 2016)
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
Initial ARV regimens are chosen based on safety, pharmacokinetic and efficacy data for drugs available in formulations suitable for the age of the child at initiation of ART. New ARV options may become available as children grow and learn to swallow pills and as new drugs, drug formulations, and data become available. For children who have sustained virologic suppression (e.g., 6–12 months) on their current regimen, changing to a new ARV regimen may be considered in order to permit use of pills instead of liquids, reduce pill burden, allow use of once-daily medications, reduce risk of adverse events, and align their regimens with widely used, efficacious adult regimens.
Several studies have addressed switching ARV regimen components in children with sustained virologic suppression. Based on the NEVEREST study, young children (i.e., aged <3 years) with virologic suppression who switch from lopinavir/ritonavir (LPV/r) to nevirapine can maintain virologic suppression as well as those who continue LPV/r, provided there is good adherence and no baseline resistance to nevirapine.1,2 In the NEVEREST 3 study, young children with history of exposure to nevirapine and with virologic suppression on ritonavir-boosted lopinavir maintained virologic suppression when switched from LPV/r to efavirenz.3 By extrapolation, replacement of LPV/r with an equally potent protease inhibitor (PI) (e.g., darunavir, atazanavir), raltegravir, or another integrase strand transfer inhibitor would likely be effective, but that has not been directly studied. Several small studies have demonstrated sustained virologic suppression and reassuring safety outcomes when drugs that have greater long-term toxicity risk are replaced with drugs that are thought to have less toxicity risk (e.g., replacing stavudine with tenofovir disoproxil fumarate, zidovudine, or abacavir; replacing PIs with non-nucleoside reverse transcriptase inhibitors), including improved lipid profiles, in small cohorts of children.4-8 Small studies have shown that children with virologic suppression on certain twice-daily regimens (i.e., abacavir, nevirapine) maintain virologic suppression if changed from twice daily to once daily (see Abacavir and Nevirapine drug sections) but show mixed results when switching LPV/r dosing from twice daily to once daily; therefore, once-daily LPV/r is not recommended.9-11
Table 13 displays examples of changes in ARV regimen components that are made for reasons of simplification, convenience and safety profile in children who have sustained virologic suppression on their current regimen. When considering such a change, it is important to ensure that a child does not have virologic treatment failure. It is also critical to consider past episodes of ART, tolerability, and all prior drug resistance testing results in order to avoid choosing new ARV drugs for which archived drug resistance would limit activity.12-16 The evidence supporting many of these ARV changes is indirect, extrapolated from data about drug performance in initial therapy or follow-on therapy after treatment failure. When such changes are made, careful monitoring (e.g., viral load measurement 2 to 4 weeks after switch to new regimen) is important to ensure that virologic suppression is maintained.
|ARV Drug(s)||Current Age||Body Size Attained||Potential ARV Regimen Change||Commentb|
|≥1 year||Any||ABC once daily||See Abacavir in Appendix A: Pediatric Antiretroviral Drug Information for full discussion.|
|ZDV or ddI (or d4Tc)
||≥1 year||N/A||ABC||Once-daily dosing (see Abacavir in Appendix A: Pediatric Antiretroviral Drug Information). Less long-term mitochondrial toxicity.|
||Pubertal maturity (i.e., SMR IV or V)||TDF
|Once-daily dosing. Less long-term mitochondrial toxicity. Co-formulation with other ARV drugs can further reduce pill burden.|
|EFV||≥12 years||≥40 kg||ATV/r
|Smaller pill (DTG), higher barrier to resistance given concern for adherence challenges developing in adolescents.|
|≥1 year||≥3 kg||RAL or ATV/r||Better palatability. Less adverse lipid effect. Lower pill burden. Once-daily dosing (ATV/r).|
|Once-daily dosing (EFV and ATV/r). Better palatability. Less adverse lipid effect. See Efavirenz in Appendix A: Pediatric Antiretroviral Drug Information regarding concerns about dosing for children <3 years.|
|Once-daily dosing possible. Lower pill burden.|
|Any Multi-Pill and/or Twice-Daily Regimen||Adolescence||For regimens with TDF: pubertal maturity (i.e., SMR IV or V)||
||Once-daily dosing. Single pill. Alignment with adult regimens.|
a This list is not exhaustive in that it does not necessarily list all potential options, but instead, shows examples of what kinds of changes can be made.
b Comments relevant to the potential ARV change listed. Does not include all relevant information. Please refer to individual drug tables for full information.
c Because of concerns about long-term adverse events, d4T may be replaced with a safer drug even before sustained virologic suppression is achieved (see Stavudine in Appendix A: Pediatric Antiretroviral Drug Information).
Key to Acronyms: 3TC = lamivudine; ABC = abacavir; ARV = antiretroviral; ATV/r = atazanavir/ritonavir; COBI = cobicistat; d4T = stavudine; ddI = didanosine; DRV/r = darunavir/ritonavir; DTG = dolutegravir; EFV = efavirenz; EVG = elvitegravir; FTC = emtricitabine; LPV/r = lopinavir/ritonavir; RAL = raltegravir; RPV=rilpivirine; SMR= sexual maturity rating (Tanner stage); TAF = tenofovir alafenamide; TDF = tenofovir disoproxil fumarate; ZDV = zidovudine