Division of Maternal/Fetal Medicine & Clinical Pharmacology, Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, MD.
Division of Maternal and Pediatric Infectious Disease, Eunice Kennedy Shriver National Institute of Child Health and Development (NICHD) at the National Institutes of Health (NIH), Bethesda, MD.
J Acquir Immune Defic Syndr. 2018 Jul 1;78(3):308-313. doi: 10.1097/QAI.0000000000001677.
Concentrations of antiretrovirals in the genital tract play a key role in preexposure 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 in HIV-infected pregnant women that include a cohort receiving rilpivirine combination regimen. Intensive pharmacokinetics 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 time points around an observed dose and measured using high-performance liquid chromatography with ultraviolet detection, [plasma; lower limit of quantification (LLQ) = 10 ng/mL] or liquid chromatography-tandem mass spectrometry (CVF; LLQ = 1 ng/mL).
A total of 24 women were included in the analysis. For all time points combined, median (interquartile range) rilpivirine concentrations were 70 ng/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 second (0.90, 90% CI: 0.61 to 1.46) and third trimesters of pregnancy compared with postpartum (0.40, 90% CI: 0.19 to 0.87). Three of 189 (1.6%) plasma samples in 2 women were below the LLQ and 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 with postpartum. CVF Rilpivirine is likely to achieve inhibitory concentrations effective for preventing peripartum HIV transmission.
抗逆转录病毒在生殖道中的浓度在暴露前预防中起着关键作用。本研究旨在描述妊娠和产后妇女生殖道中利匹韦林（Edurant）的浓度。
正在进行的国际母婴青少年艾滋病临床试验方案 P1026s 是一项针对感染艾滋病毒的孕妇的抗逆转录病毒药代动力学的前瞻性研究，其中包括一个接受利匹韦林联合方案的队列。在妊娠第二和第三 trimester 以及产后，进行了稳态下的强化药代动力学评估。在观察剂量前后的 4 个时间点采集血浆和直接抽吸的宫颈阴道分泌物（CVF）样本，并使用高效液相色谱法结合紫外检测（[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 名妇女纳入分析。所有时间点合并，CVF 中利匹韦林的中位数（四分位距）浓度为 70ng/ml（23-121），血浆中浓度为 92ng/ml（49-147）。与产后相比，妊娠第二和第三 trimester 中 CVF 至血浆 AUC（0-4）比值显著升高（0.90，90%CI：0.61-1.46）。在 2 名妇女的 189 份血浆样本中，有 3 份（1.6%）低于下限，相应的 CVF 浓度。在 13 名参与者中，有 17 份 CVF 浓度（10.6%）低于下限。未发现重大安全问题。
妊娠期间 CVF 中的利匹韦林浓度高于产后。CVF 中的利匹韦林可能达到抑制浓度，有效预防围产期 HIV 传播。
