Advances in antiretroviral therapy (ART) over the past 20 years have transformed HIV from a palliative to a chronic disease. In developed countries, mother-to-child transmission (MTCT) of HIV is now rare and current cohorts of perinatally infected children and adolescents have grown up on long-term ART. In sub-Saharan Africa, where there is ongoing MTCT, many newly infected children continue to be started on treatment early in life, and there is an expanding cohort of children who will spend the majority of childhood and adolescence on ART. As more children globally spend longer on ART, morbidity and mortality will continue to decrease, but there is a need to consider the long-term toxicity of starting lifelong treatment in the first years of life.

Treatment of young children is challenging because of high viral loads, evolving pharmacokinetics, lack of suitable drug formulations and reliance on caregivers. As prevention of mother-to-child transmission (PMTCT) services expand in developing countries an additional challenge is infant exposure to non-nucleoside reverse transcriptase inhibitor (NNRTI) drugs (such as efavirenz and nevirapine) during PMTCT, leading to frequent emergence of NNRTI-resistant virus. It is therefore recommended that young children who have been exposed to NNRTIs start a first-line ART regimen that includes a protease inhibitor (PI) instead of a NNRTI. Even in the absence of prior NNRTI exposure, PI-containing first-line ART appears to be more effective in young children and future guidelines are likely to recommend expanded use of PI-based regimens …