McIlleron Helen, Denti Paolo, Cohn Silvia, Mashabela Fildah, Hoffmann Jennifer D, Shembe Saba, Msandiwa Regina, Wiesner Lubbe, Velaphi Sithembiso, Lala Sanjay G, Chaisson Richard E, Martinson Neil, Dooley Kelly E
Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa.
Johns Hopkins University Center for Tuberculosis Research, School of Medicine, Baltimore, MD, USA.
J Antimicrob Chemother. 2017 Jul 1;72(7):2028-2034. doi: 10.1093/jac/dkx112.
Newborns of HIV-infected mothers are given daily doses of nevirapine to prevent HIV-1 acquisition. Infants born to mothers with TB should also receive TB preventive therapy. TB preventive regimens include isoniazid for 6 months or rifampicin plus isoniazid for 3 months (RH preventive therapy). The effect of concomitant RH preventive therapy on nevirapine concentrations in infants is unknown.
Tshepiso was a prospective case-control cohort study of pregnant HIV-infected women with and without TB whose newborn infants received standard doses of nevirapine for HIV prophylaxis. Infants born to mothers with TB also received RH preventive therapy. Infant plasma nevirapine concentrations were measured at 1 and 6 weeks. The effects of RH preventive therapy on nevirapine disposition were investigated in a population pharmacokinetic model.
Of 164 infants undergoing pharmacokinetic sampling, 46 received RH preventive therapy. After adjusting for weight using allometric scaling, the model estimated a 33% reduction in nevirapine trough concentrations with RH preventive therapy compared with TB-unexposed infants not receiving concomitant rifampicin and a 30% decline in trough concentrations in a typical infant between day 7 and 35 post-partum.
Rifampicin-based TB preventative treatment reduces nevirapine concentrations significantly in HIV-exposed infants. Although the nevirapine exposures required to prevent HIV acquisition in breastfeeding infants are undefined, given the potential risks associated with underdosing nevirapine in this setting, it is prudent to avoid rifampicin-based preventive therapy in HIV-exposed children receiving prophylactic nevirapine.
感染艾滋病毒母亲的新生儿每日服用奈韦拉平以预防获得HIV-1。母亲患有结核病的婴儿也应接受结核病预防性治疗。结核病预防方案包括6个月的异烟肼治疗或3个月的利福平加异烟肼治疗（利福平-异烟肼预防性治疗）。同时进行利福平-异烟肼预防性治疗对婴儿体内奈韦拉平浓度的影响尚不清楚。
Tshepiso是一项前瞻性病例对照队列研究，研究对象为感染艾滋病毒的孕妇，分为有结核病和无结核病两组，其新生儿均接受标准剂量的奈韦拉平进行艾滋病毒预防。母亲患有结核病的婴儿还接受利福平-异烟肼预防性治疗。在第1周和第6周测量婴儿血浆中的奈韦拉平浓度。在群体药代动力学模型中研究利福平-异烟肼预防性治疗对奈韦拉平处置的影响。
在164名接受药代动力学采样的婴儿中，46名接受了利福平-异烟肼预防性治疗。使用异速生长标度法校正体重后，模型估计，与未同时接受利福平治疗且未接触结核病的婴儿相比，接受利福平-异烟肼预防性治疗的婴儿奈韦拉平谷浓度降低33%，在产后第7天至35天期间，典型婴儿的谷浓度下降30%。
基于利福平的结核病预防性治疗可显著降低暴露于艾滋病毒的婴儿体内的奈韦拉平浓度。虽然预防母乳喂养婴儿感染艾滋病毒所需的奈韦拉平暴露量尚不明确，但鉴于在这种情况下奈韦拉平剂量不足存在潜在风险，对于接受预防性奈韦拉平治疗的暴露于艾滋病毒的儿童，谨慎起见应避免使用基于利福平的预防性治疗。
