Reduction of Early mortaLITY in HIV-infected African adults and children starting antiretroviral therapy: REALITY trial

开始抗逆转录病毒治疗可降低感染艾滋病毒的非洲成人和儿童的早期死亡率：REALITY 试验

• 批准号: MC_EX_G1100693
• 负责人: Diana Gibb
• 金额: $ 507.99万
• 依托单位: Medical Research Council
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2012
• 资助国家: 英国
• 起止时间: 2012 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MC_EX_G1100693
• 关键词: Reduction; Early; mortaLITY; HIV; infected

The risk of dying AFTER starting treatment with antiretrovirals(ARVs) is about 7 times higher among HIV-infected adults and children in Africa than in developed countries, particularly if immunity is poor (low CD4 cell counts), because such people often harbour infections like tuberculosis and bacterial infections which show themselves when ARVs are started and immunity improves. The question about how to reduce high early death rates when people start ARVs has been identified by doctors and the African HIV community as being very important. In the REALITY trial, we will test 3 different ways to reduce high early death rates in 1200 adults and 600 children aged 5-12 years starting ARVs with CD4 cell counts less than 100 from 4 African countries (Uganda, Kenya, Zimbabwe, Malawi). Each approach will be compared with a standard approach (like doing 3 trials in one) and we will also be able to see if all approaches can provide additional benefits if used together in a package. The questions are whether any of the following reduce the risk of early death after starting ARVs:(1)using stronger ARVs(4 instead of 3 ARVs)for the first 3 months;(2)giving preventative treatment(prophylaxis)against life-threatening infections (e.g.tuberculosis, bacterial infections, cryptococcal meningitis) for 3 months after starting ARVs; (3) giving extra food to everyone (not just those with malnutrition) for 3 months; this might also help people take their ARVs as we know many get very hungry after starting ARVs. Adults and children over 5 years will be invited to join REALITY, and if they consent, at the time of starting ARVs, they will be given either the new approach or standard of care for each of the 3 questions. This will be done at random, like tossing a coin, but by a computer. All participants will be followed for at least one year to see how well they do, as well as to find out how acceptable these extra approaches are and whether there are any side effects. We will also measure whether these new approaches are cost effective to be rolled out in Africa. Adults and children are treated together in ARV clinics across Africa and have similar HIV progression and early death rates on ARVs: including adults and children aged over 5 years in the same integrated research study will provide the most relevant answers to improve the care of future patients.

非洲感染艾滋病毒的成人和儿童在开始接受抗逆转录病毒药物治疗后死亡的风险比发达国家高7倍，特别是如果免疫力差（CD 4细胞计数低），因为这些人经常携带结核病和细菌感染等感染，这些感染在开始抗逆转录病毒药物治疗和免疫力提高时就会显现出来。医生和非洲艾滋病毒界认为，如何在人们开始使用抗逆转录病毒药物时降低高早死率的问题非常重要。在REALITY试验中，我们将测试3种不同的方法，以降低来自4个非洲国家（乌干达，肯尼亚，津巴布韦，马拉维）的1200名成人和600名年龄在5-12岁的儿童的高早期死亡率，这些儿童开始使用抗逆转录病毒药物，CD 4细胞计数低于100。每种方法都将与标准方法进行比较（例如一次进行3次试验），我们还将能够看到如果在一个包中一起使用，所有方法是否都可以提供额外的好处。问题是下列任何一种方法是否能降低开始抗逆转录病毒治疗后的早期死亡风险：（1）使用更强的抗逆转录病毒治疗（4种而不是3种抗逆转录病毒药物）;（2）给予预防性治疗（预防）对危及生命的感染（如肺结核、细菌感染、隐球菌脑膜炎）;（3）给每个人额外的食物（不仅仅是营养不良的人）3个月;这也可能有助于人们服用抗逆转录病毒药物，因为我们知道许多人在开始服用抗逆转录病毒药物后会非常饥饿。成人和5岁以上的儿童将被邀请加入REALITY，如果他们同意，在开始抗逆转录病毒药物治疗时，他们将被给予新的方法或标准的护理。这将是随机进行的，就像抛硬币一样，但由计算机完成。所有参与者将被跟踪至少一年，看看他们做得有多好，以及找出这些额外的方法是多么可接受，以及是否有任何副作用。我们还将衡量这些新方法在非洲推广是否具有成本效益。成人和儿童在非洲各地的抗逆转录病毒诊所一起接受治疗，使用抗逆转录病毒药物的艾滋病毒进展和早期死亡率相似：将成人和5岁以上儿童纳入同一项综合研究将为改善未来患者的护理提供最相关的答案。

项目成果

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.

• DOI: 10.1016/s2352-3018(18)30038-9
• 发表时间: 2018-05
• 期刊: The lancet. HIV
• 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
• 通讯作者: REALITY trial team

Causes and Timing of Mortality and Morbidity Among Late Presenters Starting Antiretroviral Therapy in the REALITY Trial.

• DOI: 10.1093/cid/cix1141
• 发表时间: 2018-03-04
• 期刊: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
• 作者: Post FA;Szubert AJ;Prendergast AJ;Johnston V;Lyall H;Fitzgerald F;Musiime V;Musoro G;Chepkorir P;Agutu C;Mallewa J;Rajapakse C;Wilkes H;Hakim J;Mugyenyi P;Walker AS;Gibb DM;Pett SL;Reduction of EArly mortaLITY in HIV-infected adults and children starting antiretroviral therapy (REALITY) Trial Team
• 通讯作者: Reduction of EArly mortaLITY in HIV-infected adults and children starting antiretroviral therapy (REALITY) Trial Team

Raltegravir-intensified initial antiretroviral therapy in advanced HIV disease in Africa: A randomised controlled trial.

• DOI: 10.1371/journal.pmed.1002706
• 发表时间: 2018-12
• 期刊: PLoS medicine
• 影响因子: 15.8
• 作者: Kityo C;Szubert AJ;Siika A;Heyderman R;Bwakura-Dangarembizi M;Lugemwa A;Mwaringa S;Griffiths A;Nkanya I;Kabahenda S;Wachira S;Musoro G;Rajapakse C;Etyang T;Abach J;Spyer MJ;Wavamunno P;Nyondo-Mipando L;Chidziva E;Nathoo K;Klein N;Hakim J;Gibb DM;Walker AS;Pett SL;REALITY trial team
• 通讯作者: REALITY trial team

Inflammatory Phenotypes Predict Changes in Arterial Stiffness Following Antiretroviral Therapy Initiation.

• DOI: 10.1093/cid/ciaa186
• 发表时间: 2020-12-03
• 期刊: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
• 作者: Kelly C;Tinago W;Alber D;Hunter P;Luckhurst N;Connolly J;Arrigoni F;Abner AG;Kamngona R;Sheha I;Chammudzi M;Jambo K;Mallewa J;Rapala A;Heyderman RS;Mallon PWG;Mwandumba H;Walker AS;Klein N;Khoo S
• 通讯作者: Khoo S

Plasma calprotectin as a biomarker of mortality at antiretroviral treatment initiation in advanced HIV - pilot study

血浆钙卫蛋白作为晚期艾滋病毒抗逆转录病毒治疗开始时死亡率的生物标志物 - 试点研究

• DOI: 10.12688/wellcomeopenres.15563.1
• 发表时间: 2020
• 期刊: Wellcome Open Research
• 作者: Kamau F