Brief Report: Hormonal Contraception Use and Cabotegravir Pharmacokinetics in HIV-Uninfected Women Enrolled in HPTN 077.
Brief Report: Hormonal Contraception Use and Cabotegravir Pharmacokinetics in HIV-Uninfected Women Enrolled in HPTN 077.
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DOI：
10.1097/qai.0000000000002409
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发表时间：
2020-09-01
期刊：
影响因子：
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通讯作者：
HPTN 077 Study Team
中科院分区：
文献类型：
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作者：
Blair CS;Li S;Chau G;Cottle L;Richardson P;Marzinke MA;Eshleman SH;Adeyeye A;Rinehart AR;Margolis D;McCauley M;Hendrix CW;Landovitz RJ;HPTN 077 Study Team
Objectives：To evaluate whether hormonal contraceptive use among cisgender women is associated with differences in PK parameters of a long-acting injection formulation of the integrase strand transfer inhibitor，cabotegravir（CAB-LA）. Setting：This is a secondary analysis of 85 cisgender women accumulated in HPTN 077，a phase 2a multicenter study that accumulated HIV-uninfected，low risk individuals in Malawi，Brazil，South Africa，and Uniteds.Methods：Participants received 4 week daily oral cabotegravir lead-in，followed by CAB-LA 800 mg injection either 12 weeks（cohort 1）or 600 mg injection either 8 weeks（after 4 weeks initial interval between injections，c在最后一次注射后，对参与者进行了52 - 76周的随访。使用广义估计方程和线性回归评估CAB-LA PK参数的差异（峰浓度、谷浓度、曲线下面积、表观终末半衰期和至定量下限的时间）和按类型分层的自我报告的激素避孕药（口服、注射、植入和其他），控制体重指数和队列。与未报告激素避孕的女性（n = 6）相比，口服避孕药（n = 18）与较低的CAB-LA峰浓度相关，但与其他PK参数的差异无关。没有其他激素避孕药类型（注射剂，植入物，和其他）与CAB-LA PK parameters.Conclusion的显着差异：虽然口服避孕药的使用与CAB-LA峰值浓度的差异，没有差异，观察到其他PK参数，这表明这种关联是不可能有临床意义。然而，这些数据强调了进一步研究CAB-LA和激素避孕药之间潜在的药物相互作用的必要性。
Objectives:To evaluate whether hormonal contraceptive use among cisgender women is associated with differences in pharmacokinetic (PK) parameters of a long-acting injectable formulation of the integrase strand transfer inhibitor, cabotegravir (CAB-LA).Setting:This is a secondary analysis of 85 cisgender women enrolled in HPTN 077, a phase 2a multicenter study that enrolled HIV-uninfected, low-risk individuals in Malawi, Brazil, South Africa, and the United States.Methods:Participants received 4-week daily oral cabotegravir lead-in, followed by CAB-LA 800 mg injection every 12 weeks (cohort 1) or 600 mg every 8 weeks (after 4-week initial interval between injections, cohort 2), over 41 weeks. Participants were followed 52–76 weeks subsequent to final injection. Generalized estimating equations and linear regression were used to evaluate differences in CAB-LA PK parameters (peak concentration, trough concentration, area under the curve, apparent terminal half-life, and time to lower limit of quantification) and self-reported hormonal contraceptive stratified by type (oral, injectable, implants, and other), controlling for body mass index and cohort.Results:Compared to women reporting no hormonal contraception (n= 6), oral contraceptive use (n= 18) was associated with lower CAB-LA peak concentration but was not associated with differences in other PK parameters. No other hormonal contraceptive type (injectable, implants, and other) was associated with significant differences in CAB-LA PK parameters.Conclusion:Although oral contraceptive use was associated with differences in CAB-LA peak concentration, no differences were observed in other PK parameters, suggesting that this association is not likely to be clinically significant. However, these data highlight the need for further research exploring potential drug–drug interactions between CAB-LA and hormonal contraceptives.