Department of Virology, Saint Louis Hospital-APHP, 75010 Paris, France.
J Clin Virol. 2010 Mar;47(3):248-52. doi: 10.1016/j.jcv.2009.12.022. Epub 2010 Jan 22.
Darunavir (DRV) is the latest protease inhibitor (PI) to be approved for antiretroviral-naive and -experienced HIV-infected patients.
We examined virologic and immunologic outcomes of highly antiretroviral-experienced patients with triple-class drug resistance receiving DRV/r-based regimens, and attempted to identify factors predictive of virologic success.
We studied patients beginning a ritonavir-boosted DRV (DRV/r 600/100mg twice daily)-containing regimen. Virologic success was defined as plasma viral load (pVL)<50copies/ml at week 36.
We studied 62 patients with very severe immunodeficiency (CDC stage C in 69% of cases; median CD4 cell nadir 12/mm(3)). They had previously received a median of four PI and had extensive PI resistance, with a median of three major PI and two DRV resistance mutations. The baseline median pVL and CD4 cell count values were 4.6log(10) and 150/mm(3). At week 36, pVL had fallen by 2.6log(10) and the CD4 cell count had risen by 123cells/mm(3). The virologic success rate was 55% overall, and was improved by concomitant first use of enfuvirtide (67%), raltegravir (69%) or etravirine (75%). Virologic success was independently associated with fewer major PI mutations, previous tipranavir exposure, and concomitant first use of enfuvirtide or raltegravir.
In these highly antiretroviral-experienced patients with triple-class drug resistance, virologic success of DRV-containing regimens was mainly associated with the use of new drug classes and/or fully active drugs. Interestingly, previous tipranavir failure did not undermine the efficacy of DRV, confirming the low level of cross-resistance and, probably, distinct resistance profiles between DRV and tipranavir.
达芦那韦（DRV）是最新批准的用于初治和经治 HIV 感染患者的蛋白酶抑制剂（PI）。
我们观察了接受 DRV/r 方案治疗的具有三重耐药性的高度经治 HIV 感染患者的病毒学和免疫学结局，并试图确定预测病毒学成功的因素。
我们研究了开始接受利托那韦增强的 DRV（DRV/r 600/100mg 每日两次）方案的患者。病毒学成功定义为第 36 周时血浆病毒载量（pVL）<50 拷贝/ml。
我们研究了 62 例严重免疫缺陷患者（69%为 CDC 分期 C 期；中位 CD4 细胞最低点 12/mm(3)）。他们之前接受过中位数为 4 种 PI 治疗，具有广泛的 PI 耐药性，其中中位数有 3 种主要 PI 和 2 种 DRV 耐药突变。基线 pVL 和 CD4 细胞计数的中位数分别为 4.6log(10)和 150/mm(3)。第 36 周时，pVL 下降了 2.6log(10)，CD4 细胞计数升高了 123 个细胞/mm(3)。总的病毒学成功率为 55%，恩夫韦地（67%）、拉替拉韦（69%）或依曲韦林（75%）联合首次应用可提高病毒学成功率。病毒学成功独立与较少的主要 PI 突变、以前使用过替拉那韦和联合首次应用恩夫韦地或拉替拉韦有关。
在这些具有三重耐药性的高度经治患者中，DRV 方案的病毒学成功率主要与新药物类别和/或完全有效的药物的使用有关。有趣的是，以前使用替拉那韦失败并没有削弱 DRV 的疗效，这证实了 DRV 和替拉那韦之间的交叉耐药水平较低，可能存在不同的耐药谱。
