Department of Epidemiology, University of Washington, Seattle, Washington, USA.
Department of Biostatistics, Vanderbilt University, Nashville, Tennessee, USA.
J Int AIDS Soc. 2022 Sep;25(9):e26001. doi: 10.1002/jia2.26001.
Contraceptive implants containing etonogestrel and levonorgestrel have emerged as popular contraceptive options among women in areas of high HIV burden in sub-Saharan Africa. However, recent pharmacokinetic data have shown drug-drug interactions between implants and efavirenz-containing antiretroviral therapy (ART), reducing the effectiveness of the implants. Here, we evaluated pregnancy incidence in 6-month intervals following implant initiation among women using efavirenz and contraceptive implants to assess whether the risk of breakthrough pregnancy is higher after specific periods of implant use.
We used data from a retrospective longitudinal analysis of women living with HIV ages 18-45 years in western Kenya who attended HIV-care facilities between 2011 and 2015. We used Cox proportional hazard models to compute hazard ratios (HRs) for breakthrough pregnancy by implant type and ART regimen. Depending on the model, we adjusted for socio-demographic and clinical factors, programme, site and interaction between calendar time and ART regimen. We utilized inverse probability weights (IPWs) to account for three sampling phases (electronic medical record [EMR], chart review and phone interview) and calculated overall parameter estimates.
Women contributed 14,768 woman-years from the largest sampling phase (EMR). The median age was 31 years. Women used etonogestrel implants for 26-69% of the time and levonorgestrel implants for 7-31% of the time, depending on the sampling phase. Women used efavirenz, nevirapine or no ART for 27-33%, 40-46% and 15-26% of follow-ups, respectively. When combining sampling phases, there was little evidence to suggest that the relative hazard of pregnancy among efavirenz-containing ART users relative to nevirapine-containing ART changed with length of time on implants: IPW-adjusted HR of 3.1 (CI: [1.5; 6.4]) at 12 months, 3.4 (CI: [1.8; 6.3]) at 24 months, 3.8 (CI: [1.9; 7.7]) at 36 months and 4.2 (CI: [1.6; 11.1]) at 48 months (interaction p-value = 0.88). Similarly, no significant change in HRs over time was found when comparing women not using ART to nevirapine-containing ART users (interaction p-value = 0.49).
We did not find evidence to suggest implants being more fallible from drug-drug interactions with efavirenz at later time intervals of implant use. Thus, we would not recommend shortening the duration of implant use or replacing implants sooner when concomitantly used with efavirenz.
在撒哈拉以南非洲艾滋病毒负担较高的地区，含有依托孕烯和左炔诺孕酮的避孕植入物已成为女性中流行的避孕选择。然而，最近的药代动力学数据显示，植入物与包含依非韦伦的抗逆转录病毒疗法（ART）之间存在药物相互作用，降低了植入物的有效性。在这里，我们评估了在开始使用依非韦伦和避孕植入物后的 6 个月间隔内的妊娠发生率，以评估在特定的植入物使用期间突破性妊娠的风险是否更高。
我们使用了来自肯尼亚西部 18-45 岁艾滋病毒感染者的回顾性纵向分析的数据，这些妇女在 2011 年至 2015 年间在艾滋病毒护理机构就诊。我们使用 Cox 比例风险模型计算了突破性妊娠的风险比（HR）按植入物类型和 ART 方案。根据模型，我们调整了社会人口统计学和临床因素、方案、地点以及日历时间和 ART 方案之间的相互作用。我们利用逆概率权重（IPW）来考虑三个抽样阶段（电子病历[EMR]、图表审查和电话访谈），并计算了总体参数估计。
女性在最大的抽样阶段（EMR）贡献了 14768 名妇女年。中位年龄为 31 岁。女性使用依托孕烯植入物的时间为 26-69%，左炔诺孕酮植入物的时间为 7-31%，具体取决于抽样阶段。女性使用依非韦伦、奈韦拉平或无 ART 的时间分别为随访时间的 27-33%、40-46%和 15-26%。当结合抽样阶段时，几乎没有证据表明依非韦伦组与奈韦拉平组相比，怀孕的相对危险度随植入物使用时间的延长而发生变化：12 个月时 IPW 调整的 HR 为 3.1（95%CI：[1.5; 6.4]），24 个月时为 3.4（95%CI：[1.8; 6.3]），36 个月时为 3.8（95%CI：[1.9; 7.7]），48 个月时为 4.2（95%CI：[1.6; 11.1]）（交互检验 p 值=0.88）。同样，与未使用 ART 的女性相比，奈韦拉平组的 HR 随时间无显著变化（交互检验 p 值=0.49）。
我们没有发现证据表明，在植入物使用的后期时间间隔内，植入物与依非韦伦的药物相互作用更容易出现故障。因此，我们不会建议在与依非韦伦同时使用时缩短植入物的使用时间或更早更换植入物。
