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

在非洲，感染艾滋病毒的成人和儿童在开始使用抗逆转录病毒药物(ARV)治疗后死亡的风险大约是发达国家的7倍，特别是如果免疫力较差(CD4细胞计数较低)，因为这些人通常携带结核病和细菌感染等感染，当ARV启动和免疫力提高时，这些感染就会显现出来。医生和非洲艾滋病毒社区已经确认，当人们开始使用抗逆转录病毒药物时，如何降低高早期死亡率的问题非常重要。在现实试验中，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名成年人和600名5-12岁儿童开始使用CD4细胞计数低于100的抗逆转录病毒药物。每种方法都将与一种标准方法进行比较(比如在一种方法中进行3次试验)，我们还将能够看到，如果在一个包中一起使用，所有方法是否都能提供额外的好处。问题是，在启动抗逆转录病毒药物后，以下任何一种措施是否可以降低过早死亡的风险：(1)在前3个月使用更强大的抗逆转录病毒药物(4个而不是3个抗逆转录病毒药物)；(2)在启动抗逆转录病毒药物后3个月内对危及生命的感染(如结核病、细菌感染、隐球菌性脑膜炎)进行预防性治疗(预防)；(3)在3个月内给每个人(不仅仅是营养不良者)额外的食物；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抗逆转录病毒药物后会非常饥饿。5岁以上的成人和儿童将被邀请加入现实，如果他们同意，在启动抗逆转录病毒药物时，他们将获得新的方法或标准的照顾，每一个问题的3个问题。这将是随机的，就像扔硬币一样，但由计算机完成。所有参与者将被跟踪至少一年，看看他们的表现如何，以及这些额外的方法是否可以接受，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，在抗逆转录病毒药物上有类似的艾滋病毒进展和早期死亡率：将成年人和5岁以上的儿童纳入同一项综合研究研究将提供最相关的答案，以改善对未来患者的护理。

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.