Changes in rapid HIV treatment initiation after national “treat all” policy adoption in 6 sub-Saharan African countries: Regression discontinuity analysis

Background
Most countries have formally adopted the World Health Organization’s 2015 recommendation of universal HIV treatment (“treat all”). However, there are few rigorous assessments of the real-world impact of treat all policies on antiretroviral treatment (ART) uptake across different contexts.
Methods and findings
We used longitudinal data for 814,603 patients enrolling in HIV care between 1 January 2004 and 10 July 2018 in 6 countries participating in the global International epidemiology Databases to Evaluate AIDS (IeDEA) consortium: Burundi (N = 11,176), Kenya (N = 179,941), Malawi (N = 84,558), Rwanda (N = 17,396), Uganda (N = 96,286), and Zambia (N = 425,246). Using a quasi-experimental regression discontinuity design, we assessed the change in the proportion initiating ART within 30 days of enrollment in HIV care (rapid ART initiation) after country-level adoption of the treat all policy. A modified Poisson model was used to identify factors associated with failure to initiate ART rapidly under treat all. In each of the 6 countries, over 60% of included patients were female, and median age at enrollment ranged from 32 to 36 years. In all countries studied, national adoption of treat all was associated with large increases in rapid ART initiation. Significant increases in rapid ART initiation immediately after treat all policy adoption were observed in Rwanda, from 44.4% to 78.9% of patients (34.5 percentage points [pp], 95% CI 27.2 to 41.7; p < 0.001), Kenya (25.7 pp, 95% CI 21.8 to 29.5; p < 0.001), Burundi (17.7 pp, 95% CI 6.5 to 28.9; p = 0.002), and Malawi (12.5 pp, 95% CI 7.5 to 17.5; p < 0.001), while no immediate increase was observed in Zambia (0.4 pp, 95% CI −2.9 to 3.8; p = 0.804) and Uganda (−4.2 pp, 95% CI −9.0 to 0.7; p = 0.090). The rate of rapid ART initiation accelerated sharply following treat all policy adoption in Malawi, Uganda, and Zambia; slowed in Kenya; and did not change in Rwanda and Burundi. In post hoc analyses restricted to patients enrolling under treat all, young adults (16–24 years) and men were at increased risk of not rapidly initiating ART (compared to older patients and women, respectively). However, rapid ART initiation following enrollment increased for all groups as more time elapsed since treat all policy adoption. Study limitations include incomplete data on potential ART eligibility criteria, such as clinical status, pregnancy, and enrollment CD4 count, which precluded the assessment of rapid ART initiation specifically among patients known to be eligible for ART before treat all.
Conclusions
Our analysis indicates that adoption of treat all policies had a strong effect on increasing rates of rapid ART initiation, and that these increases followed different trajectories across the 6 countries. Young adults and men still require additional attention to further improve rapid ART initiation.

研究背景
目前多数国家已正式采用世界卫生组织2015年提出的全民艾滋病治疗建议——「全员治疗（treat all）」。然而，针对不同场景下全员治疗政策对抗逆转录病毒治疗（antiretroviral treatment, ART）接受情况的真实世界影响，目前仍缺乏严谨的评估。

研究方法与结果
本研究纳入参与全球艾滋病流行病学数据库评估联盟（International epidemiology Databases to Evaluate AIDS, IeDEA）的6个国家2004年1月1日至2018年7月10日期间登记艾滋病诊疗的814603名患者的纵向数据，分别为布隆迪（n=11176）、肯尼亚（n=179941）、马拉维（n=84558）、卢旺达（n=17396）、乌干达（n=96286）及赞比亚（n=425246）。本研究采用准实验性断点回归设计（quasi-experimental regression discontinuity design），评估各国推行全员治疗政策后，艾滋病诊疗登记后30天内启动抗逆转录病毒治疗的比例（快速ART启动）的变化；并采用改良泊松模型，识别全员治疗政策下未能快速启动ART的相关危险因素。

纳入研究的6个国家中，患者女性占比均超60%，登记时的中位年龄为32~36岁。所有纳入研究的国家中，国家级推行全员治疗政策均与快速ART启动率的大幅提升相关。具体而言，全员治疗政策推行后即刻出现快速ART启动率显著提升的国家包括：卢旺达（从44.4%升至78.9%，提升34.5个百分点[pp]，95%置信区间[95% CI]为27.2~41.7；p<0.001）、肯尼亚（提升25.7pp，95% CI为21.8~29.5；p<0.001）、布隆迪（提升17.7pp，95% CI为6.5~28.9；p=0.002）及马拉维（提升12.5pp，95% CI为7.5~17.5；p<0.001）；而赞比亚（提升0.4pp，95% CI为-2.9~3.8；p=0.804）与乌干达（提升-4.2pp，95% CI为-9.0~0.7；p=0.090）未观察到即刻提升。

推行全员治疗政策后，马拉维、乌干达及赞比亚的快速ART启动率显著加快，肯尼亚则有所放缓，卢旺达与布隆迪无明显变化。事后分析中，仅纳入推行全员治疗政策后登记的患者，结果显示青年群体（16~24岁）与男性相较于老年患者及女性，分别更难以快速启动ART。但随着全员治疗政策推行时间的推移，所有群体的登记后快速ART启动率均有所提升。

本研究存在局限性：潜在ART入选标准相关数据不全，包括临床状态、妊娠情况及登记时CD4细胞计数（CD4 count），因此无法针对全员治疗政策推行前即符合ART指征的患者单独评估其快速启动情况。

研究结论
本研究分析表明，推行全员治疗政策对提升快速ART启动率具有显著效果，且6个国家的提升轨迹存在差异。青年群体与男性仍需额外关注，以进一步改善快速ART启动率。