促進愛滋感染者之結核病預防治療
資料來源：www.thelancet.com/hiv 2022 年 9 月 9 日 / 財團法人台灣紅絲帶基金會編譯
結核病預防性治療可大大降低 HIV 感染者罹患活動性結核病的風險。世衛組織建議 HIV 感染者接受結核病預防性治療作為 HIV照護的一部分，包括異煙肼預防性治療 (isoniazid preventive therapy , IPT)，通常每天給予進行 6 個月。儘管有此建議，但在結核病高發地區，特別是在撒哈拉以南非洲地區，結核病預防性治療的採用情況各不相同。2020 年，世衛組織非洲區域新登記的愛滋病毒感染者中有 71% 接受了結核病預防性治療；烏干達是採用率最低的國家之一（39%）。在《剌胳針愛滋病毒》中，Elijah Kakande 及其同事報告了一項集團隨機對照試驗的結果，該試驗評估了中級衛生管理人員為促進烏干達愛滋病毒感染者的 IPT 使用而進行的多管齊下的介入措施。來自 82 個地區（佔烏干達 135 個地區的 61%）的衛生管理人員（一名地區衛生官員和一名結核病主管）被納入 14 個集群（每個集群 4 到 7 個地區），其中 7 個集群（43 個地區）被隨機分配到介入組和7 個集群（39 個區）到對照組。介入措施包括與衛生管理人員形成小型合作，安排由烏干達愛滋病毒和結核病專家主持的會議、企業領導力培訓、前線工作人員和員工管理人員之間的雙向 SMS 平台之取得以促進每週報告，並在每半年一次的會議上使用儀表板來總結每個小型協作的季度進度。對照組收到了烏干達衛生部關於 IPT 的指引，並可以使用該部和聯合國兒童基金會支持的單向 SMS 系統。主要結果是 2 年以上（2019-21 年）成年的 HIV 感染者的 IPT 啟動率。獨立於試驗之外，在全國範圍內2019 年第三季度實施 IPT 的 100 天推動因與財務突發之事件相關（被要求至少數量的 HIV 感染者啟動 IPT，才能繼續獲得美國總統緊急計畫 [the US President’s Emergency Plan for AIDS Relief , PEPFAR] 的支持）。 因此，作者針對IPT採用的初期結果在進行額外的預先指定分析時排除了這一時期。次要結果包括衛生管理者的 IPT 知識和管理技能的變化、所有代表區參加照護的 HIV 感染者的結核病發生率以及子樣本中 IPT 的完成情況。在 HIV 照護中接受 IPT 的成年人的中位比例（在各自集群中兩個最大的診所）在試驗前一個季度時介入組為 1.8%（95% CI 0.4-5.2），對照組為 2.2%（0.6-5.3）。研究結果包括，當排除 100 天 IPT 推進數據時，介入對 IPT 啟動的有顯著影響：介入組啟動 IPT每人年為0.32，而對照組每人年為 0.25-（發生率比值 [IRR] 1.27, 95% CI 1.00–1.61；p=0.026）。IPT 之啟動在 100 天 IPT 推進期間顯著增加，而這縮小了兩組之間的差異。因此，在整個追蹤期間，兩組間 IPT 啟動的差異不顯著：0.74 IPT 啟動/人年與 0.65啟動/人年相比（IRR 1.14, 95% CI 0.88– 1.46；p=0.16)。值得注意的是，在 100 天 IPT 推動後（2021 年第 1 季度），包括在 COVID-19 大流行期間，介入組的 IPT 啟動率仍然較高。重要的是，在隨機化分配 1 年後（2019 年底），介入組顯示出對 IPT 功效的更多了解，並報告改善了地區內的溝通、地區間的協作，並感覺有能力更好地支持一線提供者。然而，介入並未顯示出對 IPT 完成率和 HIV 相關的結核病發生率之顯著影響。在為期 100 天的推動下，超過 500,000 名 HIV 感染者啟動了 IPT，Kakande 及其同事的研究結果顯示，啟用的大幅增加是可能是透過協調努力，改善結核病預防治療的供應以及實施夥伴的投資。儘管中層衛生管理人員通常監督國家結核病預防治療計畫，但很少有針對這一群體的介入措施。值得稱讚的是，這項研究制定了一項涉及中層衛生管理人員的介入措施，他們有助於將基於證據的政策轉化為規劃行動。本研究顯示，賦予中級衛生管理人員權力可能會克服一些衛生系統在愛滋病毒感染者的結核病預防治療上之實施障礙。頻繁的商品缺貨、衛生提供者的知識和支持不足以及難以排除活動性結核病等，都是在包括烏干達在內的高流行地區實施結核病預防治療的常見衛生系統障礙。長遠來看這種方法是否會導致參與量持續的增加仍然未知。需要更多的研究，例如 Kakande 及其同事的研究，以確定最佳方法，讓中層健康管理人員參與解決啟動結核病預防治療的系統障礙。
我們聲明沒有競爭利益。 SML 報告在提交的工作之外從默克獲得資助。我們要感謝 Grace John-Stewart（華盛頓大學）對手稿的評論。
*Sylvia M LaCourse, Dickens Onyango sylvial2@uw.edu；美國華盛頓州西雅圖華盛頓大學全球健康系(SML)，華盛頓大學醫學系過敏和傳染病科（SML）；
肯亞基蘇木縣衛生局，（DO）； 荷蘭烏得勒支大學醫學中心，Julius 健康科學和初級保健中心，Julius 國際衛生 (DO)。
Promoting tuberculosis preventive therapy in HIV
www.thelancet.com/hiv Vol 9 September 2022
Tuberculosis preventive therapy substantially reduces the risk of active tuberculosis in people living with HIV. WHO recommends people with HIV receive tuberculosis preventive therapy as part of HIV care, including isoniazid preventive therapy (IPT), which is given typically daily for 6 months. Despite this recommendation, uptake of tuberculosis preventive therapy is variable in settings with high prevalences of tuberculosis, especially in subSaharan Africa. In 2020, 71% of people with HIV who were newly enrolled in care from the WHO African region initiated tuberculosis preventive therapy; Uganda was among countries with the lowest uptake (39%). In The Lancet HIV, Elijah Kakande and colleagues report results of a cluster randomised controlled trial evaluating a multipronged intervention among midlevel health managers to promote IPT uptake among adults with HIV in Uganda. Health managers (one district health officer and one tuberculosis supervisor) from 82 districts (61% of Uganda’s 135 districts) were enrolled in 14 clusters (four to seven districts per cluster), with seven clusters (43 districts) randomised to intervention and seven clusters (39 districts) to control groups. The intervention included formation of mini-collaboratives with the health managers, with scheduled meetings facilitated by Ugandan experts in HIV and tuberculosis, business leadership training, two-way SMS platform access between frontline workers and managers to facilitate weekly reports, and use of dashboards at semiannual meetings summarising each mini-collaborative’s quarterly progress. The control group received Uganda Ministry of Health guidelines on IPT and access to a ministry and UNICEF-supported one-way SMS system. The primary outcome was IPT initiation rates among adults with HIV over 2 years (2019–21). Independent of the trial, a national, 100-day push to implement IPT occurred in the third quarter of 2019 tied to a financial contingency (a minimum number of people with HIV initiating IPT was required to continue receiving support from the US President’s Emergency Plan for AIDS Relief [PEPFAR]). Thus, the authors did additional prespecified analysis of the primary outcome of IPT uptake excluding this period. Secondary outcomes included changes in IPT knowledge and management skills among health managers, tuberculosis incidence among people with HIV enrolled in care at all represented districts, and IPT completion in a subsample. The median proportion of adults in HIV care receiving IPT (at the two largest clinics in each cluster) was 1·8% (95% CI 0·4–5·2) in the intervention group and 2·2% (0·6–5·3) in the control group during the quarter preceding trial initiation. Findings of the study include a significant effect of the intervention on IPT initiation when data for the 100-day IPT push were excluded: 0·32 IPT starts per person-year in the intervention group compared with 0·25 per person-year in the control group (incidence rate ratio [IRR] 1·27, 95% CI 1·00–1·61; p=0·026). IPT initiation increased markedly during the 100-day IPT push period, and this attenuated the difference between the two groups. Thus, in the overall followup period, the difference in IPT initiation between groups was not significant: 0·74 IPT starts per personyear compared with 0·65 per person-year (IRR 1·14, 95% CI 0·88–1·46; p=0·16). Notably, IPT initiation rates remained higher in the intervention group after the 100-day IPT push (in quarter 1 of 2021), including during the COVID-19 pandemic. Importantly, 1 year after randomisation (end of 2019), health managers in the intervention group demonstrated greater increases in knowledge of IPT efficacy and reported improved within-district communication, interdistrict collaboration, and feeling empowered to better support frontline providers. However, the intervention did not show a significant effect on IPT completion rates and HIV-associated tuberculosis incidence. With over 500000 people with HIV initiating IPT during the 100-day push, the findings by Kakande and colleagues illustrate that substantial increases in uptake are possible with coordinated efforts to improve supply of tuberculosis preventive therapy and implementing partner investment. Although mid-level health managers typically oversee national tuberculosis preventive therapy programmes, few interventions target this group. This study should be commended for developing an intervention that involves mid-level health managers, who are instrumental for translating evidence-based policies into programmatic action.9 This study shows that empowering mid-level health managers could potentially overcome some health system barriers to implementation of tuberculosis preventive therapy among people with HIV. Frequent commodity stockouts, inadequate health provider knowledge and buy-in, and difficulties in ruling out active tuberculosis are common health system barriers to implementation of tuberculosis preventive therapy in high-prevalence settings, including Uganda. Whether the approach will lead to sustained increased uptake over the longer term remains unknown. More studies such as the one by Kakande and colleagues are needed to determine optimal approaches to engage midlevel health managers in addressing system barriers to initiation of tuberculosis preventive therapy.
We declare no competing interests. SML reports grant funding from Merck outside the submitted work. We would like to acknowledge Grace John-Stewart (University of Washington) for comments on the manuscript.
*Sylvia M LaCourse, Dickens Onyango sylvial2@uw.edu
Division of Allergy and Infectious Diseases, Department of Medicine, University of Washington, Seattle, WA 98104, USA (SML); Department of Global Health, University of Washington, Seattle, WA, USA (SML);
Kisumu County Department of Health, Kisumu, Kenya (DO); Julius Global Health, Julius Centre for Health Sciences and Primary Care, University Medical Centre, Utrecht, Netherlands (DO)