ABSTRACT

The study aimed at defining protease (PR) resistance mutations associated with darunavir (DRV) failure and PR resistance evolution at DRV failure, in a large database of HIV patients. Overall, 1104 patients were included: only 118 (10.7%) failed at a median observation time of 16 months. The mean number of PR mutations at baseline was 2.7, but it was higher in patients who subsequently failed DRV (3.8 vs. 2.6). In addition the number of PR mutations increased at failure (mean 4.3). The higher statistical difference at baseline between failing vs. non-failing patients was observed for V32I and I84V mutations. At DRV failure the major increase was still observed for V32I; I54L, V11I and I50V also increased. Despite the increment in the mean number of mutations per patient between baseline and failure, in 21 patients (17.8%) at baseline and 36 (30.5%) at failure no PR mutation was detected. Different interpretation systems yielded different levels of DRV full resistance both at baseline and at failure. The HIV-DB system showed a low level of DRV full resistance, with a low increase at failure. In contrast, the Rega interpretation algorithm detected the highest proportion of full DRV resistant isolates and both Rega and ARNS algorithms detected significant differences in full DRV resistance between patients who subsequently failed versus those who responded to the DRV containing regimen. Rega and ARNS algorithms also showed a further increase in full resistance to DRV at failure, with ARNS that almost doubled the proportion of full resistant patients.
Keywords: Darunavir; Genotypic resistance; Protease inhibitors; Interpretation algorithms.

Articolo presente in – HAART and correlated pathologies n. 11 –

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