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中，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约7倍，特别是免疫力差（CD4细胞计数低）的人，因为这些人往往患有结核病和细菌感染等感染，当开始接受抗逆转录病毒药物治疗和免疫力提高时，这些感染就会显现出来。医生和非洲艾滋病社区认为，当人们开始使用抗逆转录病毒药物时，如何降低高的早期死亡率是一个非常重要的问题。在REALITY试验中，我们将在来自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5-12岁儿童中测试3种不同的方法来降低高早期死亡率，这些儿童开始接受抗逆转录病毒药物治疗，CD4细胞计数低于100。每种方法都将与标准方法进行比较（比如一次进行3个试验），我们也将能够看到如果将所有方法组合在一起使用，是否可以提供额外的好处。问题是，以下措施是否能降低开始抗逆转录病毒药物治疗后的早期死亡风险：(1)在头3个月使用更强的抗逆转录病毒药物（4种而不是3种）；(2)在开始抗逆转录病毒药物治疗后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)为每个人（不只是营养不良的人）提供3个月的额外食物；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服用抗逆转录病毒药物后会感到非常饥饿。成人和5岁以上儿童将被邀请加入REALITY，如果他们同意，在开始抗逆转录病毒药物治疗时，他们将获得针对3个问题中的每一个的新方法或标准护理。这将是随机完成的，就像扔硬币一样，但由计算机完成。所有参与者将被随访至少一年，看看他们的表现如何，以及这些额外方法的可接受程度，以及是否有任何副作用。我们还将衡量在非洲推广这些新方法是否具有成本效益。成人和儿童在非洲各地的抗逆转录病毒药物诊所一起接受治疗，并且在抗逆转录病毒药物治疗方面具有相似的艾滋病毒进展和早期死亡率：将成人和5岁以上儿童纳入同一综合研究将为改善对未来患者的护理提供最相关的答案。

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.