异烟肼联合利福喷丁预防性抗结核治疗对人类免疫缺陷病毒感染患者依非韦伦药代动力学影响的研究  

Effect of isoniazid and rifapentine anti-tuberculosis on the pharmacokinetics of efavirenz in people living with HIV

作　　者：何张玙璠 阮巧玲 杨欣平 普琳梅 邵凌云 张文宏 张云桂 杨清銮 HE Zhangyufan;RUAN Qiaoling;YANG Xinping;PU Linmei;SHAO Lingyun;ZHANG Wenhong;ZHANG Yungui;YANG Qingluan(Department of Infectious Diseases,Huashan Hospital,Fudan University,Shanghai 200040,China)

机构地区：[1]复旦大学附属华山医院感染科,上海200040 [2]云南省传染病医院结核科

出　　处：《中国感染与化疗杂志》2025年第2期162-167,共6页Chinese Journal of Infection and Chemotherapy

基　　金：上海市青年英才扬帆计划项目(22YF1404900);国家自然科学基金(82302533;82271794);云南省张文宏专家工作站(202105AF150027)。

摘　　要：目的 对人类免疫缺陷病毒(HIV)感染人群使用1个月每周3次异烟肼联合利福喷丁预防性抗结核治疗方案,评估依非韦伦药代动力学影响血药浓度和预防结核活动的有效性。方法 接受600 mg依非韦伦治疗HIV感染者同时使用包含利福喷丁(450 mg)及异烟肼(400 mg)1个月每周3次(1H3P3)的预防性抗结核治疗。分别在第0、2、4、8周进行依非韦仑血药浓度检测,第2、4周进行利福喷丁血药浓度检测,第0、8周测定血HIV-RNA。目标为依非韦伦浓度>1 mg/L,如果80%以上受试者的依非韦仑血药浓度达到目标值则认为该预防性治疗方案是可接受的。随访18个月,评估该方案的有效性。结果 共入组31例HIV感染者,其中2例受试者基线依非韦伦血药浓度<1 mg/L,鉴于依从性较差将其从药代动力学分析中剔除。其余29例受试者中23(79.3%)例为男性,年龄[中位数 (四分位数)]为43.0 (32.5,53.5)岁。第0周的依非韦伦血药浓度[中位数 (四分位数)]为2.33 (1.96,2.34) mg/L;第2周为2.32 (1.90,3.28) mg/L;第4周为2.07 (1.83,3.09)mg/L;第8周2.71(2.14,3.33)mg/L。依非韦伦在第0周、第2周、第4周、第8周四个时间点的血浆浓度差异无统计学意义(P>0.05)。第2周的利福喷丁血药浓度为9.36(6.23,16.47)mg/L;第4周为9.36(6.41,15.56)mg/L。利福喷丁第2周与第4周的血药浓度差异无统计学意义(P>0.05)。所有受试者在第2、4、8周依非韦伦的血药浓度都大于1 mg/L。此外,男性比女性依非韦伦血药浓度更低 (P<0.05);低体重(<60 kg)比高体重(≥60 kg)受试者依非韦伦血药浓度更高(P<0.05)。对受试者进行了为期18个月的随访,均未出现活动性结核症状或体征。结论 依非韦伦与1H3P3方案联合使用对依非韦伦血药浓度的影响差异无统计学意义。Objective This study aimed to evaluate the interaction between antiretroviral drug efavirenz and anti-tuberculosis 1H3P3(isoniazid plus rifapentine)in people living with HIV.Methods HIV-positive individuals on efavirenz-containing(600 mg)antiretroviral therapy(ART)received 1H3P3 regimen containing rifapentine(450 mg)plus isoniazid(400 mg)3 times a week for 1 month.Efavirenz concentrations were measured at weeks 0,2,4,8.Rifapentine concentration was determined at weeks 2 and 4.HIV RNA load was determined at weeks 0 and 8.Treatment target was efavirenz concentration>1 mg/L.The anti-TB prevention was considered acceptable if the target of efavirenz concentration was achieved in more than 80%of participants.The participants were followed up for 18 months to evaluate the efficacy of treatment.Results Thirty-one participants living with HIV were enrolled in the study.Two participants were excluded from PK analysis because his/her baseline efavirenz concentration<1 mg/L,suggesting poor treatment adherence.Evaluable PK data were available for 29 participants,including 23(79.3%)males.The median[interquartile range(IQR)]age of the participants was 43.0(32.5,53.5)years.The median(IQR)efavirenz plasma concentration was 2.33(1.96,2.34)mg/L at week 0,2.32(1.90,3.28)mg/L at week 2,2.07(1.83,3.09)mg/L at week 4,and 2.71(2.14,3.33)mg/L at week 8.Efavirenz concentration did not show significant difference between the 4 time points(P>0.05).Median(IQR)rifapentine concentration was 9.36(6.23,16.47)mg/L at week 2,and 9.36(6.41,15.56)mg/L at week 4.Rifapentine concentration did not show significant difference between week 2 and week 4(P>0.05).Efavirenz concentrations was>1 mg/L in all participants at weeks 2,4,and 8.Furthermore,efavirenz concentration was significantly higher in females and patients with body weight<60 kg compared with males and those with body weight≥60 kg(P<0.05).None of the participants had symptoms or signs of active tuberculosis during 18-month follow-up.Conclusions Isoniazid plus rifapentine(1H3P3 regimen)did n

关 键 词：依非韦伦 利福喷丁 血药浓度 人类免疫缺陷病毒 

分 类 号：R978.3[医药卫生—药品]