Hurwitz Kathleen E, Isehunwa Oluwaseyi O, Hendrickson Kayla R, Jaggernath Manjeetha, Kriel Yolandie, Smith Patricia M, Mathenjwa Mxolisi, Bennett Kara, Psaros Christina, Baeten Jared M, Bangsberg David R, Haberer Jessica E, Smit Jennifer A, Matthews Lynn T
Department of Epidemiology and Statistics, Target RWE, Durham, NC, United States.
Division of Infectious Diseases, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, United States.
Front Reprod Health. 2023 Oct 4;5:1263422. doi: 10.3389/frph.2023.1263422. eCollection 2023.
Daily, oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) as pre-exposure prophylaxis (PrEP) reduces HIV acquisition for African women. Adherence is key to efficacy and patterns of adherence can be highly variable in real-world settings. Using group-based trajectory modeling (GBTM), we sought to identify distinct patterns of periconception PrEP adherence and evaluate potential baseline predictors of such adherence trajectories.
We conducted a single-arm longitudinal study for women aged 18-35 years living in Durban, South Africa with personal or partner plans for pregnancy with a partner with HIV or of unknown serostatus. Participants were offered safer conception counseling, including daily oral PrEP; women who initiated PrEP were given a bottle with an electronic pillcap that recorded when device opens. Weekly adherence to daily PrEP was modeled using GBTM with a censored normal outcome distribution as a function of weeks since PrEP initiation. The number and functional form of the adherence trajectory groups were primarily selected based on Bayesian information criteria (BIC) and confirmed by mean estimated probabilities of group membership. A multivariable version of the selected model assessed baseline predictors of membership in adherence trajectory groups.
Overall mean (95% CI) adherence to PrEP was 63% (60%, 67%). We identified four groups of women with distinct patterns of adherence: (1) high (i.e., ≥6 doses per week) steady adherence throughout follow-up (22% of PrEP initiators); (2) moderate (i.e., 4-5 doses per week), but steady adherence (31%); (3) initially high, but consistently declining adherence (21%); and (4) initially moderate adherence, followed by a rapid decline and subsequent rebound (26%). In multivariable-adjusted analyses, older age was associated with membership in the high, steady adherence group as compared to the group identified with an adherence trajectory of initially high, then decline, and finally a rebound.
GBTM is useful for exploring potential heterogeneity in longitudinal patterns of medication adherence. Although a large proportion of women in this study achieved high levels of adherence by electronic pillcap initially, far fewer women maintained these levels consistently. Knowledge of different adherence trajectories could be used to develop targeted strategies for optimizing HIV prevention during periconception.
每日口服替诺福韦酯富马酸盐/恩曲他滨（TDF/FTC）作为暴露前预防（PrEP）可降低非洲女性感染艾滋病毒的风险。坚持服药是疗效的关键，而在现实环境中，服药依从模式可能存在很大差异。我们使用基于群体的轨迹模型（GBTM）来识别受孕前PrEP依从性的不同模式，并评估此类依从轨迹的潜在基线预测因素。
我们对居住在南非德班、年龄在18 - 35岁、本人或伴侣有怀孕计划且伴侣感染艾滋病毒或血清学状态未知的女性进行了一项单臂纵向研究。为参与者提供了更安全的受孕咨询，包括每日口服PrEP；开始服用PrEP的女性会收到一个装有电子药帽的瓶子，该药帽会记录设备打开的时间。使用GBTM对每日PrEP的每周依从性进行建模，以自开始服用PrEP以来的周数为函数，采用截尾正态结果分布。依从轨迹组的数量和函数形式主要根据贝叶斯信息准则（BIC）选择，并通过组成员身份的平均估计概率进行确认。所选模型的多变量版本评估了依从轨迹组组成员身份的基线预测因素。
PrEP的总体平均（95% CI）依从率为63%（60%，67%）。我们确定了四组具有不同依从模式的女性：（1）在整个随访期间依从性高（即每周≥6剂）且稳定（22%的PrEP启动者）；（2）中等（即每周4 - 5剂）但稳定的依从性（31%）；（3）最初依从性高，但持续下降（21%）；（4）最初依从性中等，随后迅速下降并随后反弹（26%）。在多变量调整分析中，与依从轨迹为最初高、然后下降、最后反弹的组相比，年龄较大与高且稳定依从组的组成员身份相关。
GBTM有助于探索药物依从性纵向模式中的潜在异质性。尽管本研究中有很大比例的女性最初通过电子药帽实现了高依从性，但能持续保持这些水平的女性要少得多。了解不同的依从轨迹可用于制定针对性策略，以优化受孕前的艾滋病毒预防。
