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.

View SMILE (Penta 17) publications

What is SMILE?

Strategy for Maintenance of HIV suppression with integrase inhibitor + darunavir/ritonavir in children (PENTA 17)

SMILE is a multicentre randomised study evaluating safety and antiviral effect of a once daily integrase inhibitor administered with Darunavir/Ritonavir compared to standard of care among adolescents and children living with HIV who are also virologically suppressed.

This study is sponsored by Penta and enrolled 318 children from 31 sites in 11 countries.

Why is SMILE needed?

The current standard of care includes NRTIs which have been shown to be a potent source of adverse effects in children and adolescents and requires them to take pills twice a day. Having to take medication twice a day could affect adherence, especially when adolescents take over the responsibility for administering their own treatment. Poor adherence is associated with viral load rebound and an increased risk of the development of drug resistance. It is therefore important to develop and evaluate simpler ART regimens to help improve adherence and both short and long-term outcomes for children and adolescents. Treatment simplification is also critical as this may increase access to drugs, support retention in care and reduce treatment costs.

What is SMILE’s goal?

The SMILE study will assess whether children and adolescents living with HIV who have suppressed viral loads switch from the standard of care to a fully suppressive three-drug regimen including two NRTI’s to DRV/r plus a once-daily INSTI, will maintain similar levels of viral suppression. The study hopes to improve how HIV medication is taken by children and adolescents.

Latest study news

SMILE at International Workshop on HIV Pediatrics

A reason to SMILE – we reached Last Patient Last Visit

SMILE: Enrolment target of 300 patients achieved today!

SMILE has received funding from Penta. Gilead and Janssen have provided both drugs and funding while ViiV has provided the drugs (dolutegravir).


We would like to update you on our recent activities