Effect of ready-to-use supplementary food on mortality in severely immunocompromised HIV-infected individuals in Africa initiating antiretroviral therapy (REALITY): an open-label, parallel-group, randomised controlled trial.
Effect of ready-to-use supplementary food on mortality in severely immunocompromised HIV-infected individuals in Africa initiating antiretroviral therapy (REALITY): an open-label, parallel-group, randomised controlled trial.
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DOI：
10.1016/s2352-3018(18)30038-9
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发表时间：
2018-05
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影响因子：
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通讯作者：
REALITY trial team
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作者：
Mallewa J;Szubert AJ;Mugyenyi P;Chidziva E;Thomason MJ;Chepkorir P;Abongomera G;Baleeta K;Etyang A;Warambwa C;Melly B;Mudzingwa S;Kelly C;Agutu C;Wilkes H;Nkomani S;Musiime V;Lugemwa A;Pett SL;Bwakura-Dangarembizi M;Prendergast AJ;Gibb DM;Walker AS;Berkley JA;REALITY trial team
在撒哈拉以南非洲，严重免疫功能低下的艾滋病毒感染者在开始抗逆转录病毒治疗后的头几个月内死亡风险很高。我们假设，普遍提供即用型补充食品（RUSF）将增加早期体重增加，从而降低早期死亡率相比，目前的指南建议，即用型治疗食品（RUTF）的严重营养不良的个人。我们在肯尼亚、马拉维、乌干达和津巴布韦的8家城市或城郊地区医院的住院和门诊设施中进行了一项2× 2 ×2析因、开放标签、平行组试验。 合格的参与者是ART初治成人和至少5岁的儿童，确认感染HIV，CD 4细胞计数低于100个细胞/μL，在设施中开始ART。我们随机分配参与者（1：1）开始ART（RUSF）或不（无RUSF）12周的花生基RUSF，每天含有1000千卡和微量营养素，成人每天两包92克，5-12岁儿童一包（每天500千卡），无论营养状况如何。在两组中，只有在严重营养不良的情况下（即体重指数[BMI] <16-18 kg/m2或儿童的BMI年龄Z评分<-3），才接受RUTF补充剂。我们使用计算机生成的、顺序编号的表格进行随机分组，这些表格包含在在线数据库中的不同区组大小。随机化按中心、年龄和其他两个因素随机化分层，分为12周连续性雷特格韦和加强抗感染预防（其他地方报告）。安排在第2、4、8、12、18、24、36和48周进行门诊访视，包括护士评估生命状态和症状以及分发所有药物，包括ART和RUSF。主要结果是第24周的死亡率，按意向治疗进行分析。次要结果包括体重、BMI和中上臂围（MUAC）的绝对变化。在所有随机分配的参与者中分析安全性。随访48周。本试验已在ClinicalTrials.gov（NCT 01825031）和ISRCTN注册中心（43622374）注册。在2013年6月18日至2015年4月10日期间，我们将1805名参与者随机分配到治疗组：897名接受RUSF治疗，908名接受无RUSF治疗。56例（3%）失访。96例（10.9%，95%CI 9.0 - 13.1）被分配到RUSF组的参与者和92例（10.3%，8.5 - 12.5）被分配到无RUSF组的参与者在24周内死亡（风险比1.05，95%CI 0.79 - 1.40;对数秩p= 0.75），没有证据表明与其他随机分组有相互作用（均p> 0.7）。在48周内，RUSF组中13岁及以上的成人和青少年在体重、BMI和MUAC方面的增幅显著大于非RUSF组（分别为p= 0.004、0.004和0.03）。最常见的严重不良事件类型是特异性感染，在897名分配RUSF的参与者中有90名（10%）发生，在908名分配无RUSF的参与者中有87名（10%）发生。到第48周，两组均有205名参与者发生严重不良事件（p= 0.81），RUSF组有181名参与者发生4级不良事件，而非RUSF组有172名参与者发生4级不良事件（p= 0.45）。在严重免疫功能低下的HIV感染者中，在ART开始时普遍提供RUSF，与仅向严重营养不良的个体提供RUTF相比，改善了短期体重增加，但没有死亡率。因此，目前没有必要改变政策，向所有开始抗逆转录病毒治疗的严重免疫功能低下的艾滋病毒感染者提供营养补充。联合全球健康试验计划（英国医学研究理事会、英国国际发展部和威康信托基金会）。
In sub-Saharan Africa, severely immunocompromised HIV-infected individuals have a high risk of mortality during the first few months after starting antiretroviral therapy (ART). We hypothesise that universally providing ready-to-use supplementary food (RUSF) would increase early weight gain, thereby reducing early mortality compared with current guidelines recommending ready-to-use therapeutic food (RUTF) for severely malnourished individuals only. We did a 2 × 2 × 2 factorial, open-label, parallel-group trial at inpatient and outpatient facilities in eight urban or periurban regional hospitals in Kenya, Malawi, Uganda, and Zimbabwe. Eligible participants were ART-naive adults and children aged at least 5 years with confirmed HIV infection and a CD4 cell count of fewer than 100 cells per μL, who were initiating ART at the facilities. We randomly assigned participants (1:1) to initiate ART either with (RUSF) or without (no-RUSF) 12 weeks' of peanut-based RUSF containing 1000 kcal per day and micronutrients, given as two 92 g packets per day for adults and one packet (500 kcal per day) for children aged 5–12 years, regardless of nutritional status. In both groups, individuals received supplementation with RUTF only when severely malnourished (ie, body-mass index [BMI] <16–18 kg/m2 or BMI-for-age Z scores <–3 for children). We did the randomisation with computer-generated, sequentially numbered tables with different block sizes incorporated within an online database. Randomisation was stratified by centre, age, and two other factorial randomisations, to 12 week adjunctive raltegravir and enhanced anti-infection prophylaxis (reported elsewhere). Clinic visits were scheduled at weeks 2, 4, 8, 12, 18, 24, 36, and 48, and included nurse assessment of vital status and symptoms and dispensing of all medication including ART and RUSF. The primary outcome was mortality at week 24, analysed by intention to treat. Secondary outcomes included absolute changes in weight, BMI, and mid-upper-arm circumference (MUAC). Safety was analysed in all randomly assigned participants. Follow-up was 48 weeks. This trial is registered with ClinicalTrials.gov (NCT01825031) and the ISRCTN registry (43622374). Between June 18, 2013, and April 10, 2015, we randomly assigned 1805 participants to treatment: 897 to RUSF and 908 to no-RUSF. 56 (3%) were lost-to-follow-up. 96 (10·9%, 95% CI 9·0–13·1) participants allocated to RUSF and 92 (10·3%, 8·5–12·5) to no-RUSF died within 24 weeks (hazard ratio 1·05, 95% CI 0·79–1·40; log-rank p=0·75), with no evidence of interaction with the other randomisations (both p>0·7). Through 48 weeks, adults and adolescents aged 13 years and older in the RUSF group had significantly greater gains in weight, BMI, and MUAC than the no-RUSF group (p=0·004, 0·004, and 0·03, respectively). The most common type of serious adverse event was specific infections, occurring in 90 (10%) of 897 participants assigned RUSF and 87 (10%) of 908 assigned no-RUSF. By week 48, 205 participants had serious adverse events in both groups (p=0·81), and 181 had grade 4 adverse events in the RUSF group compared with 172 in the non-RUSF group (p=0·45). In severely immunocompromised HIV-infected individuals, providing RUSF universally at ART initiation, compared with providing RUTF to severely malnourished individuals only, improved short-term weight gain but not mortality. A change in policy to provide nutritional supplementation to all severely immunocompromised HIV-infected individuals starting ART is therefore not warranted at present. Joint Global Health Trials Scheme (UK Medical Research Council, UK Department for International Development, and Wellcome Trust).