In parallel, 19 patients (83%) experienced significant increases in their CD4 T-cell counts, which ranged from 50 to 90% of the baseline values. Interestingly, no patients presented severe immunosuppression after etravirine-based treatment.

The median follow-up time for etravirine-based treatment was 48.4 weeks (IQR 35.7–63.4 weeks). Eight patients (35%) were exposed for >60 weeks, and four of these had a follow-up time of >120 weeks. Of note, these four patients included boosted darunavir in their regimens. Etravirine-based mTOR inhibitor therapy was replaced in three patients because of insufficient virological and immune responses. Interestingly, at baseline, these patients harboured the following etravirine-associated resistance mutations: Y181I, G190A and K101E plus G190A/S, respectively. No deaths, AIDS-defining illnesses, or symptoms of severe intolerance were recorded. Laboratory abnormalities, adherence and antiretroviral-related adverse events are summarized in Table 1. New potent therapeutic options are needed for paediatric patients who are vertically infected with HIV-1 and harbour highly drug-resistant viruses. The

newest alternative drugs for treatment of HIV-1 infection are etravirine, raltegravir (Isentress®, NVP-BGJ398 cell line Merck Sharp & Dohme, Whitehouse Station, NJ, USA), maraviroc (Selcentry®, New York, NY, USA; still under evaluation in ongoing clinical trials for the paediatric population) and darunavir (Prezista®, Tibotec, Beerse, Belgium; recently approved for children

aged≥6 years and adolescents). In adults, etravirine-based therapy has demonstrated durable antiretroviral activity [2–4]. However, to date, no interim data have been published on efficacy and tolerability in paediatric patients harbouring multidrug resistance mutations. The present study represents a relevant assessment of the efficacy of etravirine-based therapy in paediatric patients in clinical Aspartate practice. The virological response achieved during the first 4 months of follow-up was strong and durable, with a high proportion of responders. However, as stated above, poor adherence and an extended resistance profile could abrogate the activity of etravirine-based therapy. Moreover, specific resistance mutations have been described for non-B subtype viruses. In particular, the child harbouring a C subtype, who was initially treated in Mozambique with suboptimal control of HIV-1 replication because of limited access to antiretrovirals [10], did not respond to etravirine. The recently described E138A mutation, along with an accumulation of baseline resistance mutations observed in our patient, might have compromised susceptibility to etravirine in patients with non-B subtypes [11]. Restored immunological function was observed in all initially severely immunocompromised patients.