Discontinuing cotrimoxazole preventive therapy in HIV-infected adults who are stable on antiretroviral treatment in Uganda (COSTOP): A randomised placebo controlled trial.
Discontinuing cotrimoxazole preventive therapy in HIV-infected adults who are stable on antiretroviral treatment in Uganda (COSTOP): A randomised placebo controlled trial.
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DOI：
10.1371/journal.pone.0206907
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发表时间：
2018-01-01
期刊：
影响因子：
3.7
通讯作者：
Munderi, Paula
中科院分区：
文献类型：
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作者：
Anywaine, Zacchaeus;Levin, Jonathan;Munderi, Paula
背景：复方新诺明 (CTX) 预防性治疗 (CPT) 可减少 HIV 感染患者的机会性感染和疟疾。在非洲，抗逆转录病毒治疗 (ART) 期间持续 CPT 的政策因国家而异。我们评估了乌干达接受 ART 治疗的稳定患者停止 CPT 的安全性。方法：COSTOP 是一项双盲安慰剂对照试验。年龄≥18岁、接受CPT且接受ART稳定的患者（CD4计数≥250个细胞/μL）；随机接受每日口服安慰剂（PLC 组）或复方新诺明 960 mg/片（CTX 组）。共同主要结局为：(i) 首次复方新诺明可预防感染的时间，PLC 的非劣效性定义为调整后风险比 (aHR) ≤ 1.25 的单侧 95% 置信限上限； (ii) 发生一级 3/4 血液学不良事件的时间。 结果：纳入了 2180 名受试者（1091 名 PLC；1089 名 CTX）。 932 PLC 和 943 CTX 经过最短 12 个月的随访后完成了试验。 98 名参与者（59 PLC；39 CTX）经历了 120 起复方新诺明可预防的事件，主要是细菌性肺炎（72 起事件，4 起死亡 PLC）； （48 起事件，2 起死亡 CTX）。每个方案人群中首次事件发生时间的 aHR 为 1.57（单侧上限 95% 置信限 2.21）（ITT 人群中的结果类似）。 551 名参与者（318 名 CTX；233 名 PLC）经历了 1043 起血液学不良事件（616 名 CTX；427 名 PLC）。 CTX 组出现首次不良事件（主要是中性粒细胞减少症）的时间较短（aHR 0.70 95%CI 0.59-0.82；对数秩 chi2 = 18.08；P
BACKGROUND: Cotrimoxazole (CTX) preventive therapy (CPT) reduces opportunistic infections and malaria in HIV-infected patients. In Africa, policies on sustained CPT during antiretroviral therapy (ART) differ between countries. We assessed the safety of discontinuing CPT in stable patients on ART in Uganda.METHODS: COSTOP was a double-blind placebo-controlled trial. Patients aged ≥18 years, on CPT, and stable on ART (CD4 counts ≥250 cells/muL); were randomised to daily oral placebo (PLC group) or cotrimoxazole 960 mg/tablet (CTX group). Co-primary outcomes were: (i) time to first cotrimoxazole-preventable infection, with non- inferiority of PLC defined as the upper one-sided 95% confidence limit of the adjusted hazard ratio(aHR) ≤1.25; and (ii) time to first grade 3/4 haematological adverse event.FINDINGS: 2180 subjects (1091 PLC; 1089 CTX) were enrolled. 932 PLC and 943 CTX completed the trial after 12 months minimum follow up. Ninety-eight participants (59 PLC; 39 CTX) experienced 120 cotrimoxazole- preventable events, mainly bacterial pneumonia (72 events, 4 deaths PLC); (48 events, 2 deaths CTX). The aHR for time to first event was 1.57 (upper one-sided 95% confidence limit 2.21) in per protocol population (similar results in ITT population). 551 participants (318 CTX; 233 PLC) experienced 1043 haematological adverse events (616 CTX; 427 PLC). Time to the first adverse event, mainly neutropenia, was shorter in the CTX group (aHR 0.70 95%CI 0.59-0.82; log-rank chi2 = 18.08; P