Healthy Families Quantitative Datasets and Data Dictionaries

Background In Uganda, fertility rates and adult HIV prevalence are high, and many women conceive with partners living with HIV. PrEP reduces HIV acquisition for women and, therefore, infants. We developed the Healthy-Families-PrEP intervention to support PrEP use as part of HIV prevention during periconception-pregnancy periods. We conducted a longitudinal cohort study to evaluate oral PrEP use among women participating in the intervention. Methods and Findings We enrolled HIV-negative women with plans for pregnancy with a partner living, or thought to be living, with HIV (2017-2020) to evaluate PrEP use among women participating in the Healthy-Families intervention. Quarterly study visits through 9 months included HIV and pregnancy testing, and HIV prevention counseling. PrEP was provided in electronic pillboxes, providing the primary adherence measure (“high” adherence when pillbox was opened >80% of days). Enrollment questionnaires assessed factors associated with PrEP use. Plasma tenofovir (TFV) and intraerythrocytic TFV-diphosphate (TFV-DP) concentrations were determined quarterly for women who acquired HIV and a randomly selected subset of those who did not; concentrations TFV >40ng/mL and TFV-DP >600fmol/punch were categorized as “high”. Women who became pregnant were initially exited from the cohort by design; from April 2019, women with incident pregnancy remained in the study with quarterly follow-up until pregnancy outcome. Primary outcomes included (1) PrEP uptake (proportion who initiated PrEP) and (2) PrEP adherence (proportion of days with pillbox openings during the first 3 months following PrEP initiation). We used univariable and multivariable-adjusted linear regression to evaluate baseline predictors selected based on our conceptual framework of mean adherence over 3 months. We also assessed mean monthly adherence over 9 months of follow-up and during pregnancy. We enrolled 131 women with mean age 28.7 years (95% CI:27.8-29.5). Ninety-seven (74%) reported a partner with HIV and 79 (60%) reported condomless sex. Most women (N=118; 90%) initiated PrEP. Mean electronic adherence during the 3 months following initiation was 87% (95% CI:83%, 90%). No covariates were associated with 3-month pill-taking behavior. Concentrations of plasma TFV and TFV-DP were high among 66% and 47%, 56% and 41%, and 45% and 45% at months 3, 6, and 9, respectively. We observed 53 pregnancies among 131 women (1-year cumulative incidence 53% [95% CI:43%, 62%]) and one HIV-seroconversion in a non-pregnant woman. Mean pillcap adherence for PrEP users with pregnancy follow-up (N=17) was 98% (95% CI:97%, 99%). Study design limitations include lack of a control group. Conclusions Women in Uganda with PrEP indications and planning for pregnancy chose to use PrEP. By electronic pillcap, most were able to sustain high adherence to daily oral PrEP prior to and during pregnancy. Differences in adherence measures highlight challenges with adherence assessment; serial measures of TFV-dp in whole blood suggest 41-47% of women took sufficient periconception PrEP to prevent HIV. These data suggest that women planning for and with pregnancy should be prioritized for PrEP implementation, particularly in settings with high fertility rates and generalized HIV epidemics. Future iterations of this work should compare the outcomes to current standard of care.

背景 在乌干达，生育率与成人HIV感染率均处于较高水平，且诸多女性的伴侣为HIV感染者，此类女性受孕的情况较为普遍。暴露前预防（PrEP）可降低女性及婴儿的HIV感染风险。我们开发了健康家庭-暴露前预防（Healthy-Families-PrEP）干预方案，旨在将PrEP使用作为围受孕期-妊娠期HIV预防的一部分予以支持。我们开展了一项纵向队列研究，以评估参与该干预方案的女性的口服PrEP使用情况。方法与结果 2017年至2020年间，我们纳入了计划受孕且伴侣为HIV感染者或疑似HIV感染者的HIV阴性女性，以评估参与健康家庭干预方案的女性的PrEP使用情况。研究在9个月随访周期内每季度开展一次访视，内容涵盖HIV及妊娠检测、艾滋病预防咨询。研究人员为受试者配备了电子药盒，以此作为主要的依从性评估指标：当药盒打开天数占总计划服药天数比例超过80%时，判定为“高依从性”。入组问卷用于评估与PrEP使用相关的影响因素。对于发生HIV感染的受试者，以及未发生感染的随机抽样受试者，研究人员每季度检测其血浆替诺福韦（tenofovir, TFV）及红细胞内替诺福韦二磷酸酯（intraerythrocytic TFV-diphosphate, TFV-DP）浓度；当血浆TFV浓度＞40ng/mL且TFV-DP浓度＞600fmol/punch时，判定为“高浓度”。按照研究初始设计，妊娠女性会被退出队列；但自2019年4月起，发生新发妊娠的女性仍可留在研究中，每季度接受随访直至明确妊娠结局。本研究的主要结局指标包括：（1）PrEP启动率（启动PrEP的受试者占总受试者的比例）；（2）PrEP依从性（PrEP启动后前3个月内，药盒打开天数占计划服药天数的比例平均值）。我们采用单变量及多变量校正线性回归模型，基于3个月平均依从性的概念框架筛选基线预测因子。此外，我们还评估了9个月随访期间及妊娠期间的平均月度依从性。本研究共纳入131名女性，平均年龄28.7岁（95%置信区间（CI）:27.8-29.5）。其中97人（74%）报告其伴侣为HIV感染者，79人（60%）报告存在无保护性行为。绝大多数女性（N=118；90%）启动了PrEP治疗。启动后前3个月的电子药盒依从性平均值为87%（95%置信区间（CI）:83%, 90%）。未发现任何协变量与3个月的服药行为相关。在第3、6、9个月，血浆TFV及TFV-DP浓度达标的受试者占比分别为66%与47%、56%与41%、45%与45%。131名女性中共发生53例妊娠，1年累积发病率为53%（95%置信区间（CI）:43%, 62%）；仅1名非妊娠女性发生HIV血清转换。接受妊娠随访的PrEP使用者（N=17）的平均药盒依从性为98%（95%置信区间（CI）:97%, 99%）。本研究的设计局限性在于未设置对照组。结论 在乌干达，有PrEP适应证且计划受孕的女性会选择使用PrEP。通过电子药盒监测结果可见，绝大多数女性在孕前及妊娠期均能坚持每日口服PrEP并保持高依从性。不同依从性评估方法的差异凸显了依从性评估面临的挑战；全血TFV-DP的连续检测结果显示，41%~47%的女性服用了足够剂量的围受孕期PrEP，足以达到HIV预防效果。本研究数据提示，应将计划妊娠及已妊娠的女性作为PrEP推广的优先人群，尤其是在生育率高且艾滋病广泛流行的地区。未来的相关研究应将本研究结果与当前的标准护理方案进行对比。