Sequencing of antiretroviral therapy in children in low- and middle-income countries.

PURPOSE OF REVIEW: With recent changes in global pediatric HIV policy to initiate treatment immediately after early infant diagnosis, there will be greater demand for feasible antiretroviral sequencing strategies that will support children through adulthood. This review will discuss HIV treatment (antiretroviral therapy) failure, regimen switching, and sequencing approaches in children.

RECENT FINDINGS: Although children appear to acquire resistance mutations in a similar pattern to adults, they may develop virologic failure more rapidly; reports from Africa and Asia have already documented rates as high as 26% at 12 months of antiretroviral therapy. Ritonavir-boosted lopinavir is recommended after failure to nonnucleoside reverse transcriptase inhibitors; efavirenz is the preferred nonnucleoside reverse transcriptase inhibitor after protease inhibitor failure. Approaches to sequencing nucleoside reverse transcriptase inhibitors are more complicated, as accumulated resistance mutations may render currently recommended combinations less potent. Salvage regimens are preferably selected after genotyping, and may require the use of expensive, novel boosted protease inhibitors and new drug classes (e.g., integrase inhibitors).

SUMMARY: Data on drug resistance in children in low- and middle-income countries are emerging and will guide future sequencing strategies. Lack of access to treatment monitoring and second-line and salvage drugs are key limiting factors that need to be addressed in order to ensure ongoing treatment success.