Rilpivirine Plasma and Cervicovaginal Concentrations in Women During Pregnancy and Postpartum.
Rilpivirine Plasma and Cervicovaginal Concentrations in Women During Pregnancy and Postpartum.
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DOI：
10.1097/qai.0000000000001677
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发表时间：
2018-07-01
期刊：
影响因子：
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通讯作者：
IMPAACT P1026s Protocol Team
中科院分区：
文献类型：
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作者：
Eke AC;Chakhtoura N;Kashuba A;Best BM;Sykes C;Wang J;Stek AM;Smith E;Calabrese S;Capparelli EV;Mirochnick M;IMPAACT P1026s Protocol Team
生殖道中抗逆转录病毒药物（ARV）的浓度在暴露前预防中发挥着关键作用。本研究旨在描述孕妇和产后妇女生殖道中利匹韦林 (Edurant®) 的浓度。国际母婴青少年艾滋病临床试验方案 P1026 是一项正在进行的前瞻性研究，针对 HIV 感染孕妇进行抗逆转录病毒药代动力学 (PK)，其中包括接受利匹韦林联合治疗方案的队列。在妊娠中期和晚期以及产后期间，在稳定状态下进行了密集的 PK 评估。在观察剂量周围的 4 个时间点收集血浆和直吸宫颈阴道液 (CVF) 样品，并使用高效液相色谱法和紫外检测（血浆；定量下限 (LLQ) = 10ng/mL）或液相色谱-串联质谱法（CVF；LLQ = 1ng/mL）进行测量。共有 24 名女性参与了分析。对于所有时间点，CVF 中利匹韦林浓度中位数（四分位数范围，IQR）为 70 ng/ml（23-121），血浆中为 92 ng/ml（49-147）。与产后相比，妊娠第 2 个月（0.90，90% CI 0.61–1.46）和第 3 个月的 CVF 与血浆 AUC（0-4）比率显着较高（0.40，90% CI 0.19–0.87）。两名女性的 189 个血浆样本中有 3 个 (1.6%) 低于 LLQ 以及相应的 CVF 浓度。 13 名参与者中另外 17 名 CVF 浓度 (10.6%) 低于 LLQ。没有发现重大安全问题。与产后相比，怀孕期间 CVF 中的利匹韦林浓度较高。 CVF 利匹韦林可能达到有效预防围产期 HIV 传播的抑制浓度。
Concentrations of antiretrovirals (ARVs) in the genital tract play a key role in pre-exposure prophylaxis. This study aims to describe rilpivirine (Edurant®) concentrations in the genital tract in pregnant and postpartum women. International Maternal Pediatric Adolescent AIDS Clinical Trials Protocol P1026s is an ongoing, prospective study of antiretroviral pharmacokinetics (PK) in HIV infected pregnant women that include a cohort receiving rilpivirine combination regimen. Intensive PK evaluations were performed at steady state during the second and third trimester, and postpartum. Plasma and directly-aspirated cervicovaginal fluid (CVF) samples were collected at 4 timepoints around an observed dose, and measured using high-performance liquid chromatography with ultraviolet detection, (plasma; lower limit of quantification (LLQ) = 10ng/mL) or liquid chromatography-tandem mass spectrometry (CVF; LLQ = 1ng/mL). A total of 24 women were included in the analysis. For all time points combined, median (Interquartile range, IQR) rilpivirine concentrations were 70ng/ml (23–121) in CVF and 92 ng/ml (49–147) in plasma. The CVF to plasma AUC (0-4) ratios were significantly higher in the 2nd (0.90, 90% CI 0.61–1.46) and 3rd trimesters of pregnancy compared to postpartum (0.40, 90% CI 0.19–0.87). Three of 189 (1.6%) plasma samples in two women were below the LLQ as well as the corresponding CVF concentrations. Seventeen additional CVF concentrations (10.6%) were below LLQ in 13 participants. No major safety concerns were noted. Rilpivirine concentrations were higher in the CVF during pregnancy compared to postpartum. CVF Rilpivirine is likely to achieve inhibitory concentrations effective for preventing peripartum HIV transmission.