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Original article

The prevalence of darunavir-associated mutations in HIV-1-infected children in the UK

Katherine L Donegan, A Sarah Walker, David Dunn, Ali Judd, Deenan Pillay, Esse Menson, Hermione Lyall, Gareth Tudor-Williams, Diana M Gibb, on behalf of the Collaborative HIV Paediatric Study, and the UK HIV Drug Resistance Database

Corresponding author name: Ali Judd
Corresponding author e-mail: a.judd@ctu.mrc.ac.uk

Citation: Antiviral Therapy 2012; 17:599-603
doi: 10.3851/IMP2015

Date accepted: 08 August 2011
Date published online: 15 December 2011

Abstract

Background: We examined the prevalence of ritonavir-boosted darunavir (DRV) resistance-associated mutations (RAMs) in HIV-infected children in the UK to determine the drug’s potential clinical utility as a first-line or second-line protease inhibitor (PI).

Methods: The prevalence of DRV RAMs, identified from IAS 2010 and Stanford, and the Stanford susceptibility score, were estimated in PI-naive and PI-experienced children in the Collaborative HIV Paediatric Study and the UK HIV Drug Resistance Database 1998–2008. Associations between type/duration of PI exposure and area under the viraemia curve on PI with the number of RAMs were investigated using multivariate Poisson regression.

Results: A total of 17/417 (4%) children with a resistance test when PI-naive had one IAS DRV RAM, and 1 had a Stanford mutation; none had multiple DRV RAMs. A total of 177 PI-experienced children had a test after a median 2.7 years (IQR 1.1–5.2) on PIs; 19 (11%) had one IAS DRV RAM, 7 (4%) had two RAMs, 1 (0.6%) had three RAMs and 1 (0.6%) had four RAMs. DRV RAMs were independently associated with increased years on a PI, a larger area under the viraemia curve since starting PIs, and any exposure to PIs other than lopinavir (all P0.05). Only 6 (3%) PI-experienced children had intermediate-level DRV/ritonavir resistance; none had high-level resistance.

Conclusions: DRV resistance was negligible in PI-naive children and those with lopinavir PI exposure alone. However resistance increased with increasing time, and with higher levels of viraemia, on PIs. Once-daily DRV/ritonavir would be valuable as a second PI or an alternative first PI, particularly if coformulated with a booster in an appropriate formulation for children.

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