Pham Michelle, Wickremasingha Prachi, Vargo Ryan, Patel Munjal, Nedrow Katherine, Homony Brenda, Robertson Michael N, Plank Rebeca M
Merck & Co., Inc., Rahway, NJ, USA.
J Acquir Immune Defic Syndr. 2025 Apr 22;99(4):374-8. doi: 10.1097/QAI.0000000000003678.
People living with, or at risk of acquiring, HIV-1 may use hormonal long-acting reversible contraceptives (LARCs). Islatravir is a nucleoside reverse transcriptase translocation inhibitor in development for the treatment of HIV-1. We aimed to evaluate the effects of once-monthly oral islatravir on the pharmacokinetics of LARCs.
This was an exploratory substudy of a double-blind, randomized, placebo-controlled, Phase 2a trial of once-monthly oral islatravir in adults at low risk of HIV-1 infection (MK-8591-016; NCT04003103).
Participants were randomized 2:2:1 to receive 6 once-monthly doses of oral islatravir 60 mg, oral islatravir 120 mg, or placebo. At randomization, participants using an etonogestrel-releasing implant, injectable medroxyprogesterone acetate, or injectable norethindrone enanthate could enroll in the LARC substudy. LARC use was not a stratification factor. Plasma samples for hormone concentrations were collected at normally scheduled study visits and assayed using high-performance liquid chromatographic-tandem mass spectrometric methods.
The analyses included 36 participants (etonogestrel, n = 8; medroxyprogesterone acetate, n = 20; norethindrone enanthate, n = 9; one participant was in 2 groups due to contraceptive change mid-study). No differences in hormone concentrations were observed between islatravir groups and placebo. Although sampling was insufficient to characterize full pharmacokinetics parameters, hormone concentrations were above the thresholds for contraceptive effectiveness for 94.4% (34/36) of participants.
Coadministration with once-monthly islatravir does not appear to affect exposure to LARCs in people at low risk of HIV-1 infection. Due to the exploratory nature of this substudy, prospective studies are needed to verify these findings.
感染HIV-1或有感染风险的人群可能会使用长效可逆激素避孕法（LARC）。伊斯拉曲韦是一种正在研发用于治疗HIV-1的核苷类逆转录酶易位抑制剂。我们旨在评估每月口服一次伊斯拉曲韦对LARC药代动力学的影响。
这是一项对HIV-1感染低风险成年人进行的每月口服一次伊斯拉曲韦的双盲、随机、安慰剂对照2a期试验（MK-8591-016；NCT04003103）的探索性子研究。
参与者按2:2:1随机分组，分别接受6次每月口服一次的60毫克伊斯拉曲韦、120毫克伊斯拉曲韦或安慰剂。在随机分组时，使用依托孕烯释放植入剂、醋酸甲羟孕酮注射剂或庚酸炔诺酮注射剂的参与者可参加LARC子研究。是否使用LARC不是分层因素。在正常安排的研究访视时采集血浆样本检测激素浓度，并使用高效液相色谱 - 串联质谱法进行分析。
分析纳入了36名参与者（依托孕烯组，n = 8；醋酸甲羟孕酮组，n = 20；庚酸炔诺酮组，n = 9；一名参与者因研究中期避孕方法改变同时属于两组）。伊斯拉曲韦组和安慰剂组之间未观察到激素浓度差异。虽然采样不足以完整表征药代动力学参数，但94.4%（34/36）的参与者激素浓度高于避孕有效性阈值。
每月一次服用伊斯拉曲韦似乎不会影响HIV-1感染低风险人群对LARC的暴露。由于该子研究的探索性，需要进行前瞻性研究来验证这些发现。
