Early antiretroviral therapy for HIV-infected patients admitted to an intensive care unit (EARTH-ICU): A randomized clinical trial.,PLOS ONE

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Early antiretroviral therapy for HIV-infected patients admitted to an intensive care unit (EARTH-ICU): A randomized clinical trial.
PLOS ONE ( IF 2.9 ) Pub Date : 2020-09-21 , DOI: 10.1371/journal.pone.0239452
Márcio M Boniatti ₁ , José Augusto S Pellegrini ₁ , Leonardo S Marques ₂ , Josiane F John ₁ , Luiz G Marin ₂ , Lina R D M Maito ₃ , Thiago C Lisboa ₄ , Lucas P Damiani ₅ , Diego R Falci ₆

Affiliation

Background

Highly active antiretroviral therapy (HAART) has reduced HIV-related morbidity and mortality at all stages of infection and reduced transmission of HIV. Currently, the immediate start of HAART is recommended for all HIV patients, regardless of the CD4 count. There are several concerns, however, about starting treatment in critically ill patients. Unpredictable absorption of medication by the gastrointestinal tract, drug toxicity, drug interactions, limited reserve to tolerate the dysfunction of other organs resulting from hypersensitivity to drugs or immune reconstitution syndrome, and the possibility that subtherapeutic levels of drug may lead to viral resistance are the main concerns. The objective of our study was to compare the early onset (up to 5 days) with late onset (after discharge from the ICU) of HAART in HIV-infected patients admitted to the ICU.

Methods

This was a randomized, open-label clinical trial enrolling HIV-infected patients admitted to the ICU of a public hospital in southern Brazil. Patients randomized to the intervention group had to start treatment with HAART within 5 days of ICU admission. For patients in the control group, treatment should begin after discharge from the ICU. The patients were followed up to determine mortality in the ICU, in the hospital and at 6 months. The primary outcome was hospital mortality. The secondary outcome was mortality at 6 months.

Results

The calculated sample size was 344 patients. Unfortunately, we decided to discontinue the study due to a progressively slower recruitment rate. A total of 115 patients were randomized. The majority of admissions were for AIDS-defining illnesses and low CD4. The main cause of admission was respiratory failure. Regarding the early and late study groups, there was no difference in hospital (66.7% and 63.8%, p = 0.75) or 6-month (68.4% and 79.2%, p = 0.20) mortality. After multivariate analysis, the only independent predictors of in-hospital mortality were shock and dialysis during the ICU stay. For the mortality outcome at 6 months, the independent variables were shock and dialysis during the ICU stay and tuberculosis at ICU admission.

Conclusions

Although the early termination of the study precludes definitive conclusions being made, early HAART administration for HIV-infected patients admitted to the ICU compared to late administration did not show benefit in hospital mortality or 6-month mortality.

ClinicalTrials.gov, NCT01455688. Registered 20 October 2011, https://clinicaltrials.gov/show/NCT01455688

中文翻译：

接受重症监护病房（EARTH-ICU）感染HIV的患者的早期抗逆转录病毒疗法：一项随机临床试验。

背景

高效的抗逆转录病毒疗法（HAART）在感染的所有阶段均降低了与HIV相关的发病率和死亡率，并减少了HIV的传播。目前，无论CD4数量如何，建议所有HIV患者立即开始HAART。但是，对于重症患者开始治疗存在一些担忧。主要的胃肠道药物吸收，药物毒性，药物相互作用，对药物过敏或免疫重建综合症导致的其他器官功能障碍的储备有限，以及亚治疗水平的药物可能导致病毒抵抗的可能性是主要的关注。

方法

这是一项随机，开放标签的临床试验，招募了巴西南部一家公立医院ICU住院的HIV感染患者。随机分配到干预组的患者必须在ICU入院后5天内开始进行HAART治疗。对于对照组患者，从ICU出院后应开始治疗。随访患者以确定ICU，医院和6个月时的死亡率。主要结局是医院死亡率。次要结果是6个月时的死亡率。

结果

计算的样本量为344例患者。不幸的是，由于招聘速度逐渐降低，我们决定中止该研究。共有115名患者被随机分组。大部分入院者为定义艾滋病的疾病和低CD4。入院的主要原因是呼吸衰竭。对于早期和晚期研究组，住院死亡率（66.7％和63.8％，p = 0.75）或6个月（68.4％和79.2％，p = 0.20）的死亡率无差异。经过多变量分析，ICU住院期间，院内死亡的唯一独立预测因素是休克和透析。对于6个月时的死亡率结果，独立变量是在ICU住院期间的休克和透析以及在ICU入院时的结核病。