AP-HP, Hôpital Bichat-Claude Bernard, Laboratoire de Pharmaco-Toxicologie, Paris, France.
IAME, UMR 1137, Université Paris Diderot, Sorbonne Paris Cité and INSERM, Paris, France.
J Antimicrob Chemother. 2017 Nov 1;72(11):3167-3171. doi: 10.1093/jac/dkx275.
Sub-optimal penetration of antiretroviral drugs in genital compartments might promote local HIV persistence and increase the risk of HIV transmission.
To describe the penetration of maraviroc, raltegravir, raltegravir glucuronide and rilpivirine in seminal plasma and cervico-vaginal secretions (CVS) and to assess local antiretroviral efficacy in HIV-1-positive patients.
This was a prospective, multicentre study. Inclusion criteria were HIV-1 positive, age >18 years, receiving regimens containing maraviroc and/or raltegravir and/or rilpivirine for >1 month, and good self-reported adherence. Paired blood and genital samples were collected 12 h (raltegravir and maraviroc) or 24 h (rilpivirine) post-dose. These concentrations were determined (UPLC-MS/MS) in blood and seminal plasma (total and unbound) and CVS (total, dried spots) and HIV-RNA was quantified in paired blood and genital samples.
Among the 54 enrolled patients, 15 received maraviroc (6 men), 27 received raltegravir (14 men) and 20 received rilpivirine (10 men), corresponding to 54 total and 52 unbound plasma concentrations, 29 total CVS samples and 23 total and 18 unbound seminal plasma samples. Maraviroc and raltegravir displayed a ratio of genital fluids/plasma concentrations >0.5 in both male and female genital tracts. Conversely, rilpivirine displayed a low ratio. Antiretroviral free fractions were consistent with historical data. Nine patients had blood plasma HIV-RNA >50 copies/mL (2/9 had sub-optimal antiretroviral blood plasma exposure) and two other patients had detectable HIV-RNA in genital fluids.
Maraviroc and raltegravir demonstrated good penetration in genital compartments, yielding good local virological response in genital compartments, whereas rilpivirine presented a low penetration profile but good local response.
抗逆转录病毒药物在生殖部位的渗透不足可能会促进局部 HIV 的持续存在，并增加 HIV 传播的风险。
描述马拉维若、雷特格韦、雷特格韦葡萄糖醛酸和利匹韦林在精液和宫颈阴道分泌物（CVS）中的渗透情况，并评估 HIV-1 阳性患者的局部抗逆转录病毒疗效。
这是一项前瞻性、多中心研究。纳入标准为 HIV-1 阳性、年龄>18 岁、接受含有马拉维若和/或雷特格韦和/或利匹韦林的治疗方案>1 个月且自我报告良好的依从性。在给药后 12 小时（雷特格韦和马拉维若）或 24 小时（利匹韦林）采集血样和生殖部位样本。采用超高效液相色谱-串联质谱法（UPLC-MS/MS）测定血样和精液（总浓度和游离浓度）以及 CVS（总浓度、干燥斑点）中的浓度，并定量配对血样和生殖部位样本中的 HIV-RNA。
在纳入的 54 例患者中，15 例接受马拉维若（6 例男性）治疗，27 例接受雷特格韦（14 例男性）治疗，20 例接受利匹韦林（10 例男性）治疗，共获得 54 个总血浆浓度和 52 个游离血浆浓度、29 个 CVS 总样本和 23 个总精液样本和 18 个游离精液样本。马拉维若和雷特格韦在男性和女性生殖道中均显示生殖液/血浆浓度比值>0.5。相反，利匹韦林的比值较低。游离抗逆转录病毒药物分数与历史数据一致。9 例患者的血浆 HIV-RNA>50 拷贝/mL（2/9 例患者的抗逆转录病毒血浆暴露不足），另外 2 例患者的生殖部位液体中可检测到 HIV-RNA。
马拉维若和雷特格韦在生殖部位有良好的渗透，在生殖部位产生了良好的局部病毒学反应，而利匹韦林的渗透情况较差，但局部反应良好。
