SMILE (PENTA 17)
Research type
Research Study
Full title
SMILE: Strategy for Maintenance of HIV suppression with elvitegravir+darunavir/ritonavir in children (PENTA 17). A two-arm, Phase 2/3 multicentre, open-label, randomised study evaluating safety and antiviral effect of current standard antiretroviral therapy compared to elvitegravir (EVG) administered with darunavir/ritonavir (DRV/r) in HIV-1 infected, virologically suppressed paediatric participants.
IRAS ID
186642
Contact name
Karen Scott
Contact email
Sponsor organisation
PENTA Foundation
Eudract number
2013-001476-37
ISRCTN Number
ISRCTN11193709
Clinicaltrials.gov Identifier
Duration of Study in the UK
3 years, 0 months, 1 days
Research summary
Research Summary
Taking HIV medicines every day without missing a dose is important in order to stop the virus becoming resistant to HIV medicines which can happen if the virus levels in the blood are not kept low. However, some young people find it hard to take several medications every day, especially if this is more than once a day. Newer HIV medicines which are taken once daily include Prezista (also called darunavir) which is taken with a small dose of Norvir (ritonavir) and elvitegravir.
Elvitegravir is from a new class of medicines called “integrase inhibitor). Using different classes of medicines may reduce the possibility of side effects which can be caused by long-term use of a particular class of medicine (“nucleoside reverse transcriptase inhibitors” – NRTIs). Some of the older NRTIs are associated with long term symptoms, such as fat loss in the face and limbs. The SMILE study will check whether it is ok for children to take a combination that does not include an NRTI.
In SMILE we will check whether these new medicines are safe and effective in comparison with the usual HIV medications. The trial will recruit 300 HIV-1 infected children aged 6 to <18 from Western and Eastern Europe, South Africa, Thailand, Uganda and Latin America. Participants must have had a low virus level for at least the prior 12 months and have been on a combination of medicines including 2 NRTIs and boosted PI/NNRTI for at least 24 weeks with no evidence of resistance to darunavir or integrase inhibitors.. Half the children will change to Prezista + Norvir + elvitegravir (Group 1) and half the children will continue with their current HIV medicines (Group 2). The will last 48 weeks after the last patient has been enrolled.Summary of Results
The results of the trial showed that the SMILE drug combination were just as good at treating HIV as the usual medicines that are already used to treat HIV. The SMILE drugs were also just as safe as usual medicines.
The trial results showed that children and adolescents taking the SMILE medicines gained more weight and had a slightly lower CD4 count (the cells that help keep the immune system strong) than children taking their usual medicines. However, it is not yet known whether this makes a difference to your child’s overall health and prompts further follow-up investigations.
Participants that failed on the SMILE regimen (and who had a resistance test available) did not have any occurrence of major IAS PI or INSTI mutations.
SMILE provides important data supporting the option of this NRTI-sparing regimen in children. The results support further investigation of INSTI+DRV/r dual therapy for children with treatment failure.
REC name
London - Central Research Ethics Committee
REC reference
16/LO/0680
Date of REC Opinion
14 Jul 2016
REC opinion
Further Information Favourable Opinion