Orrell Catherine, Cohen Karen, Conradie Francesca, Zeinecker Jennifer, Ive Prudence, Sanne Ian, Wood Robin
Desmond Tutu HIV Centre, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa.
Antivir Ther. 2011;16(4):527-34. doi: 10.3851/IMP1780.
Increasing efavirenz (EFV) dose from 600 mg to 800 mg daily has been suggested with concomitant rifampicin (RFN), as induction of cytochrome P450 isoenzymes may reduce EFV plasma concentrations.
Individuals from the CIPRA-South Africa cohort taking EFV-based antiretroviral therapy with concomitant tuberculosis (TB) were dosed with either increased (800 mg) or standard (600 mg) dose EFV during TB treatment. After TB therapy, all individuals took 600 mg EFV. Two mid-dosing interval EFV concentrations were determined from each individual: after 4 weeks of concomitant EFV and RFN therapy, and ≥4 weeks after TB therapy completion. Mid-dosing interval EFV concentrations were compared within individuals using the Wilcoxon signed-rank test.
Paired samples were collected from 72 individuals. Overall, 45 (63%) were women and median weight was 59 kg (IQR 52-67). At antiretroviral therapy start, median CD4(+) T-cell count was 114 cells/mm(3) (IQR 37-165), median viral load was 5.5 log (IQR 5.1-5.9). A total of 38 (53%) individuals took 800 mg EFV during TB treatment and 34 (47%) took 600 mg. EFV concentrations in the 800 mg group were higher with RFN (2.9 mg/l [IQR 1.8-5.6]) than without (2.1 mg/l [IQR 1.4-3.0]; P=0.0003). There was no significant difference in EFV concentrations with RFN (2.4 mg/l [IQR 1.2-5.1]) or without (2.2 mg/l [IQR 1.4-3.7]) in the 600 mg group. There was no increase in EFV-linked adverse effects in either group. The proportion of virologically suppressed individuals at 48 weeks was similar in both groups.
EFV concentrations were significantly increased in the EFV 800 mg group on RFN. There was no significant decrease in EFV concentrations when on RFN in the 600 mg group. Dose escalation of EFV 600 mg to 800 mg is not required during concomitant TB therapy in South Africa.
有人建议，在同时使用利福平（RFN）时，将依非韦伦（EFV）的每日剂量从600毫克增加到800毫克，因为细胞色素P450同工酶的诱导可能会降低EFV的血浆浓度。
来自南非CIPRA队列中接受以EFV为基础的抗逆转录病毒疗法并同时患有结核病（TB）的个体，在结核病治疗期间接受增加剂量（800毫克）或标准剂量（600毫克）的EFV治疗。结核病治疗后，所有个体均服用600毫克EFV。从每个个体中测定两个给药间隔中期的EFV浓度：在EFV和RFN联合治疗4周后，以及结核病治疗完成后≥4周。使用Wilcoxon符号秩检验比较个体内给药间隔中期的EFV浓度。
从72名个体中收集了配对样本。总体而言，45名（63%）为女性，中位体重为59千克（四分位间距52 - 67）。在开始抗逆转录病毒治疗时，CD4(+) T细胞计数中位数为114个细胞/立方毫米（四分位间距37 - 165），病毒载量中位数为5.5 log（四分位间距5.1 - 5.9）。共有38名（53%）个体在结核病治疗期间服用800毫克EFV，34名（47%）服用600毫克。800毫克组中与RFN同时使用时的EFV浓度（2.9毫克/升[四分位间距1.8 - 5.6]）高于不与RFN同时使用时（2.1毫克/升[四分位间距1.4 - 3.0]；P = 0.0003）。600毫克组中与RFN同时使用时的EFV浓度（2.4毫克/升[四分位间距1.2 - 5.1]）与不与RFN同时使用时（2.2毫克/升[四分位间距1.4 - 3.7]）无显著差异。两组中与EFV相关的不良反应均未增加。两组在48周时病毒学抑制个体的比例相似。
在与RFN同时使用时，800毫克EFV组的EFV浓度显著升高。600毫克组在与RFN同时使用时，EFV浓度没有显著降低。在南非，结核病合并治疗期间，无需将EFV的剂量从600毫克增加到800毫克。
