Current antiretroviral therapy (ART) guidelines recommend three ART drugs as the treatment of choice in adults, adolescents and children living with HIV. In adolescents and children, the standard treatment regimens include 2 nucleoside or nucleotide reverse transcriptase inhibitors (NRTIs) with either a non-nucleoside reverse transcriptase inhibitor (NNRTI) or a boosted protease inhibitor (PI). Whilst treatment has dramatically improved disease outcome, it has important limitations in terms of pill burden, twice daily dosing and side effects which are challenging especially in children born with HIV because they take ART for life from a young age. Children may also be more vulnerable to adverse effects due to the metabolic changes related to growth.