Darunavir-associated mutations in PI-naive and PI-experienced children in the UK

Polly Clayden, HIV i-Base

Katherine Boyd and colleagues from the Collaborative HIV Paediatric Study (CHIPS) and the UK HIV Drug Resistance Database looked at the prevalence of duranavir associated mutations in children.

As duranavir boosted by ritonavir (DRV/r) has the potential for first or second line PI use in the UK, Identifying the prevalence of resistance associated mutations (RAM) in children is important for determining the clinical utility of this drug.

In this study, data from CHIPS (a cohort of approximately 95% of reported HIV-positive children in UK/Ireland since 1996) and the UK drug resistance database from 2000–2007 were combined.

The investigators identified DRV RAM from the 2008 IAS mutations list (V11I, V32I, L33F, I47V, I50V, I54L/M, T74P, L76V, I84V, L89V) and the Stanford database (I47A, G73S/T/C, I84A/C, V82F).

The prevalence of RAM was estimated in both PI and PI-naive children. Using multivariate linear regression, the investigators examined the time on a PI, the area under the viraemia curve, and the type of PI. They used the Stanford database algorithm to assess the children’s resistance to DRV/r.

Of 344 children tested when they were PI-naive, 14 (3%) had a single RAM (2 V11I, 2 V32I, 1 I47A, 7 I50V, 1 G73S, 1 L89V). No child had more than one RAM. Of 156 PI-experienced children tested while receiving a PI, 21(13%) had one RAM, 5 (3%) had 2, and 3 (2%) had 3: 55 (35%) children received prior LPV/r only, median (IQR) 2.6 (1.2 to 5.0) years on PI.

In multivariate analysis, there were significant associations between greater number of DRV/r RAM and longer time on a PI (RR 1.14, p=0.04 +1 year), larger area under the viraemia curve since the start of PI (RR 1.78, p=0.01), and previous use of a PI other than LPV/r (RR 6.15, p=0.02 vs LPV/r only).

The investigators noted, only 3 (2%) PI-experienced children had intermediate level resistance to DRV/r using Stanford. They concluded that these results suggest that DRV/r is useful both a first PI and an alternative second PI as prevalence resistance is low.

Ref: Boyd K et al. Prevalence of Darunavir-associated Mutations in PI-naive and PI-experienced HIV-1-infected Children in the UK. 17th CROI, 16-19 February 2010, San Francisco. Poster abstract 851.

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