Medical Unit, Médecins Sans Frontières/Doctors Without Borders, New York, New York, United States of America.
PLoS One. 2012;7(9):e44793. doi: 10.1371/journal.pone.0044793. Epub 2012 Sep 28.
In HIV-infected patients receiving rifampicin-based treatment for tuberculosis (TB), the dosage of lopinavir/ritonavir (LPV/r) is adjusted to prevent sub-therapeutic lopinavir concentrations. In this setting, South African clinicians were advised to administer super-boosted LPV/r (400 mg/400 mg) twice daily, instead of standard dosed LPV/r (400 mg/100 mg) twice daily. We sought to determine--in routine practice--the tolerability and HIV treatment outcomes associated with super-boosted LPV/r compared to unadjusted LPV/r in combination with rifampicin-based TB treatment.
METHODOLOGY/PRINCIPLE FINDINGS: We conducted a retrospective review of HIV-infected patients who receiving second-line ART with a LPV/r-containing regimen who required concomitant TB treatment. We identified 29 patients; the median age was 36 years (IQR 29-40), 22 (76%) were female, the median CD4 cell count and viral load at first-line ART failure was 86 cells/mm³ (IQR 21-159) and 39,457 copies/mL (IQR 6,025-157,500), respectively. According to physician preference, 15 (52%) of 29 patients received super-boosted LPV/r (400 mg/400 mg) every 12 hours during TB treatment and 14 (48%) of 29 patients received standard dose LPV/r (400 mg/100 mg) twice daily during TB treatment. Among patients who received super-boosted LPV/r there was a trend towards a higher rate of symptomatic transaminitis (27% vs. 7%; p = 0.3), gastrointestinal toxicity (20% vs. 0%; p = 0.2) and a significantly increased need for treatment discontinuation (47% vs. 7%; p = 0.035. The durability of coadministered treatment was significantly shorter in patients who received super-boosted lopinavir/ritonavir with TB treatment compared to patients who received standard lopinavir/ritonavir dosing (log rank, P = 0.036). The rate of virologic failure was not higher in patients with unadjusted LPV/r dosing.
CONCLUSIONS/SIGNIFICANCE: We observed a high rate of toxicity and need for treatment discontinuation among patients on standard rifampicin-based TB treatment who received super-boosted LPV/r.
在接受利福平为基础的抗结核治疗的 HIV 感染者中，洛匹那韦/利托那韦（LPV/r）的剂量需要进行调整，以防止洛匹那韦浓度低于治疗范围。在这种情况下，南非临床医生建议使用强化 LPV/r（400 mg/400 mg），每日两次，而不是标准剂量 LPV/r（400 mg/100 mg），每日两次。我们旨在确定——在常规实践中——与未经调整的 LPV/r 联合利福平为基础的 TB 治疗相比，强化 LPV/r 的耐受性和 HIV 治疗结果。
方法/原理发现：我们对接受 LPV/r 为基础的二线 ART 治疗且需要同时进行 TB 治疗的 HIV 感染者进行了回顾性研究。我们共纳入了 29 名患者；中位年龄为 36 岁（IQR 29-40），22 名（76%）为女性，一线 ART 失败时的中位 CD4 细胞计数和病毒载量分别为 86 个/立方毫米（IQR 21-159）和 39,457 拷贝/毫升（IQR 6,025-157,500）。根据医生的偏好，29 名患者中的 15 名（52%）在接受 TB 治疗期间接受了强化 LPV/r（400 mg/400 mg），每 12 小时一次，29 名患者中的 14 名（48%）在接受 TB 治疗期间接受了标准剂量 LPV/r（400 mg/100 mg），每日两次。在接受强化 LPV/r 的患者中，有症状性肝转氨酶升高（27% vs. 7%；p=0.3）、胃肠道毒性（20% vs. 0%；p=0.2）和治疗中断的需求明显增加（47% vs. 7%；p=0.035）的趋势。与接受标准 LPV/r 剂量的患者相比，接受强化 LPV/r 联合 TB 治疗的患者联合治疗的持续时间明显缩短（对数秩检验，P=0.036）。未调整 LPV/r 剂量的患者病毒学失败率并不更高。
结论/意义：我们观察到在接受标准利福平为基础的 TB 治疗的患者中，使用强化 LPV/r 治疗的患者出现毒性和需要治疗中断的比例较高。
