SOD Malattie Infettive, Azienda Ospedaliera Universitaria Careggi, Largo Brambilla 3, 50134, Firenze, Italy.
Infection. 2012 Jun;40(3):311-8. doi: 10.1007/s15010-011-0237-y. Epub 2012 Jan 12.
This 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 treatment-experienced human immunodeficiency virus (HIV) patients.
Overall, 1,104 patients were included: 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. In addition, the number of PR mutations increased at failure. The increase in the mean number of mutations was completely related to mutations considered to be associated with DRV resistance following the indications of the main DRV clinical trials.
The higher statistical difference at baseline between failing versus non-failing patients was observed for the V32I and I84V mutations. At DRV failure, the major increase was still observed for V32I; I54L, V11I, T74P 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.
The HIV-DB interpretation algorithm identified few patients with full DRV resistance at baseline and few patients developed full resistance at DRV failure, indicating that complete resistance to DRV is uncommon.
本研究旨在确定蛋白酶（PR）耐药突变与达芦那韦（DRV）失败相关，并在一个大型治疗经验丰富的人类免疫缺陷病毒（HIV）患者数据库中定义 DRV 失败时 PR 耐药进化。
共有 1104 名患者被纳入：118 名（10.7%）在中位观察时间为 16 个月时失败。基线时 PR 突变的平均数量为 2.7，但在随后 DRV 失败的患者中更高。此外，在失败时 PR 突变数量增加。突变数量的增加与主要 DRV 临床试验指示的与 DRV 耐药相关的突变完全相关。
在失败与非失败患者之间，基线时 V32I 和 I84V 突变的统计学差异更高。在 DRV 失败时，仍观察到 V32I 的主要增加；I54L、V11I、T74P 和 I50V 也增加。尽管患者从基线到失败时每个患者的平均突变数量增加，但在 21 名（17.8%）基线时和 36 名（30.5%）失败时未检测到 PR 突变。
HIV-DB 解释算法确定了少数患者在基线时具有完全的 DRV 耐药性，少数患者在 DRV 失败时发展为完全耐药性，表明对 DRV 的完全耐药性并不常见。
