Dados do Trabalho

Título

Effect of the relationship between anaemia and systemic inflammation on the risk of incident tuberculosis and death in people with advanced HIV: a sub-analysis of the REMEMBER trial

Introdução

Tuberculosis (TB) is an infectious morbidity that commonly occurs in people living with HIV (PWH) and increases the progression of HIV disease and the risk of death. Anaemia frequently affects PWH and/or TB. Nevertheless, the impact of this condition on incident TB and death in PWH is not fully characterized. Simple progression markers are needed to identify those at the highest risk for poor outcomes.

Objetivo (s)

This study aimed to assess how baseline severity of anaemia and associated inflammatory profiles impact death and the incidence of TB in a cohort of PWH who received TB preventive therapy (TPT).

Material e Métodos

This study is a secondary posthoc analysis of the AIDS Clinical Trials Group A5274 REMEMBER clinical trial (NCT0138008), an open-label randomised clinical trial of antiretroviral-naïve PWH with CD4<50 cells/µL, performed from October 31, 2011 to June 9, 2014, from 18 outpatient research clinics in 10 low- and middle-income countries (Malawi, South Africa, Haiti, Kenya, Zambia, India, Brazil, Zimbabwe, Peru, and Uganda) who initiated antiretroviral therapy and either isoniazid TPT or 4-drug empiric TB therapy. Plasma concentrations of several soluble inflammatory biomarkers were measured prior to the commencement of antiretroviral and anti-TB therapies, and participants were followed up for at least 48 weeks. Incident TB or death during this period were primary outcomes. We performed multidimensional analyses, logistic regression analyses, survival curves, and Bayesian network analyses to delineate associations between anaemia, laboratory parameters, and clinical outcomes.

Resultados e Conclusão

Of all 269 participants, 76·2% (n=205) were anaemic, and 31·2% (n=84) had severe anaemia. PWH with moderate/severe anaemia exhibited a pronounced systemic pro-inflammatory profile compared to those with mild or without anaemia, hallmarked by a substantial increase in IL-6 plasma concentrations. Moderate/severe anaemia was also associated with incident TB incidence (aOR: 3·59, 95%CI: 1·32-9·76, p=0·012) and death (aOR: 3·63, 95%CI: 1·07-12·33, p=0·039). Our findings suggest that PWH with moderate/severe anaemia display a distinct pro-inflammatory profile. Moderate/severe anaemia is a risk factor for incident TB and significantly increases the risk of death. PWH with anaemia should be monitored closely to minimise the occurrence of unfavourable outcomes.

Palavras-chave

HIV, incident TB, anaemia, inflammation, death

Agradecimentos

Participants, ACTG trial sites (A5274 REMEMBER trial) and the National Institutes of Health.