Hospital Pitié-Salpêtrière, Infectious Diseases Department, 75013 Paris, France.
Sorbonne University, UPMC Univ Paris 06, INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique (IPLESP UMRS 1136), 75013 Paris, France.
J Antimicrob Chemother. 2018 Feb 1;73(2):490-493. doi: 10.1093/jac/dkx417.
Darunavir/ritonavir is a potent PI with a high genetic barrier and pharmacological robustness favourably investigated as monotherapy. Whether darunavir could be dose reduced in the context of monotherapy deserves investigation.
Patients with HIV suppressed viraemia (plasma viral load <50 copies/mL for 12 months) under ART who had switched to darunavir/ritonavir monotherapy at 600/100 mg/day between 2013 and 2015 were included in this observational 48 week single-centre study. The primary outcome was the proportion of patients with virological success (defined as plasma viral load <50 copies/mL) at week 24. Secondary outcomes included treatment strategy success and resistance.
Thirty-one patients were included with the following baseline characteristics [median (IQR)]: age 52 years (47-57), CD4+ 649 cells/mm3 (463-813), ART duration 16.3 years (9.2-22.3), nadir CD4+ 195 cells/mm3 (144-261) and duration of HIV suppression 7.8 years (4.8-9.7). Prior to switch, ART consisted of PI monotherapy for 28 of 31 patients [darunavir/ritonavir 800/100 mg/day (n = 26), lopinavir/ritonavir (n = 1) and atazanavir/ritonavir (n = 1)] and a triple drug regimen for 3 of 31 patients. Within the 48 weeks of follow-up, no virological failure occurred and two patients discontinued 600/100 mg of darunavir/ritonavir due to side effects at week 16 and 40, leading to a virological suppression rate of 100% (95% CI = 89-100) at weeks 24 and 48. Strategy success rates were 96.8% (95% CI = 83.3-99.9) at week 24 and 93.5% (95% CI = 78.6-99.2) at week 48. Median (IQR) Ctrough values of 800/100 mg of darunavir/ritonavir and 600/100 mg of darunavir/ritonavir were 1537 ng/mL (1286-1724) and 1255 ng/mL (873-2161), respectively.
A lower dose of darunavir/ritonavir used as monotherapy (600/100 mg/day) was highly effective in virologically suppressed HIV-infected patients. Further studies are needed to confirm these data.
达芦那韦/利托那韦是一种强效的 PI，具有较高的遗传屏障和药理学稳健性，作为单药治疗得到了很好的研究。达芦那韦在单药治疗的情况下是否可以减少剂量值得研究。
本观察性、48 周、单中心研究纳入了 2013 年至 2015 年间因病毒学抑制（血浆病毒载量<50 拷贝/ml 持续 12 个月）而接受抗逆转录病毒治疗（ART）的患者，他们将达芦那韦/利托那韦（600/100mg/天）转换为单药治疗。主要结局是第 24 周时病毒学成功（定义为血浆病毒载量<50 拷贝/ml）的患者比例。次要结局包括治疗策略的成功和耐药性。
31 例患者纳入本研究，具有以下基线特征[中位数（IQR）]：年龄 52 岁（47-57）、CD4+细胞计数 649 个/mm3（463-813）、ART 持续时间 16.3 年（9.2-22.3）、CD4+细胞计数最低点 195 个/mm3（144-261）和 HIV 抑制持续时间 7.8 年（4.8-9.7）。在转换之前，ART 包括 28 例患者的 PI 单药治疗[达芦那韦/利托那韦 800/100mg/天（n=26）、洛匹那韦/利托那韦（n=1）和阿扎那韦/利托那韦（n=1）]和 3 例患者的三药治疗方案。在 48 周的随访期间，没有发生病毒学失败，有 2 例患者因副作用在第 16 周和第 40 周停用 600/100mg 的达芦那韦/利托那韦，导致第 24 周和第 48 周的病毒抑制率分别为 100%（95%CI=89-100）和 100%（95%CI=89-100）。第 24 周和第 48 周时治疗策略的成功率分别为 96.8%（95%CI=83.3-99.9）和 93.5%（95%CI=78.6-99.2）。达芦那韦/利托那韦 800/100mg 和 600/100mg 的中位（IQR）Ctrough 值分别为 1537ng/ml（1286-1724）和 1255ng/ml（873-2161）。
达芦那韦/利托那韦的低剂量（600/100mg/天）作为单药治疗在病毒学抑制的 HIV 感染患者中非常有效。需要进一步的研究来证实这些数据。
