UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

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

Post, FA; Szubert, AJ; Prendergast, AJ; Johnston, V; Lyall, H; Fitzgerald, F; Musiime, V; ... Pett, SL; + view all (2018) Causes and Timing of Mortality and Morbidity Among Late Presenters Starting Antiretroviral Therapy in the REALITY Trial. Clinical Infectious Diseases , 66 (S2) S132-S139. 10.1093/cid/cix1141. Green open access

[thumbnail of Post_cix1141.pdf]
Preview
Text
Post_cix1141.pdf - Published Version

Download (561kB) | Preview

Abstract

BACKGROUND: In sub-Saharan Africa, 20%-25% of people starting ART have severe immunosuppression; ~10% die within three months. In the recently-reported REALITY randomized trial, a broad enhanced anti-infection prophylaxis bundle reduced all-cause mortality versus cotrimoxazole alone; here, we investigate in detail the contribution and timing of different causes of mortality/morbidity. METHODS: Participants started ART with CD4 <100 cells/mm3; enhanced-prophylaxis comprised cotrimoxazole plus 12 weeks’ isoniazid+fluconazole, single-dose albendazole and 5-days azithromycin. A blinded endpoint review committee adjudicated events and causes of death as (non-mutually exclusively) tuberculosis, cryptococcosis, severe bacterial infections (SBI), other potentially azithromycin-responsive infections, other events, and unknown (deaths only). RESULTS: Median pre-ART CD4 was 37 cells/mm3. 225/1805(12.7%) participants died by week-48. Fatal/non-fatal events occurred early (median 4.0(IQR2.0-11.7) weeks post-ART initiation), then rates declined exponentially. 154 deaths had single and 71 multiple causes, including tuberculosis in 80(4.5%) participants, cryptococcosis 20(1.1%), SBI 33(1.9%), other potentially-azithromycin-responsive infections 23(1.3%), other events 63(3.6%) and unknown 88(5.0%). Enhanced-prophylaxis reduced deaths from cryptococcosis (p=0.03) and unknown causes (p=0.03) but not tuberculosis, SBI, potentially azithromycin-responsive infections or other causes (p>0.3). Enhanced-prophylaxis reduced incidence of non-fatal/fatal tuberculosis (p=0.007) and cryptococcosis (p=0.03), but not SBI, other potentially-azithromycin-responsive infections or other events (p>0.2). By week-48, rates were lowest (<1/100 person-years [PY]) for cryptococcosis, moderate (1-5/100PY) for tuberculosis, SBI, other potentially-azithromycin-responsive events and unknown deaths, and highest (>5/100PY) for other events. CONCLUSIONS: Enhanced-prophylaxis reduced mortality from cryptococcosis and unknown causes and non-fatal tuberculosis and cryptococcosis. High early incidence of fatal/non-fatal events highlights the need for starting enhanced-prophylaxis with ART in advanced disease.

Type: Article
Title: Causes and Timing of Mortality and Morbidity Among Late Presenters Starting Antiretroviral Therapy in the REALITY Trial
Open access status: An open access version is available from UCL Discovery
DOI: 10.1093/cid/cix1141
Publisher version: https://doi.org/10.1093/cid/cix1141
Language: English
Additional information: Copyright © 2018 World Health Organization; licensee Oxford University Press USA. This is an open access article distributed under the terms of the Creative Commons Attribution IGO License (http://creativecommons. org/licenses/by/3.0/igo/legalcode), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Keywords: HIV; Africa; antiretroviral therapy; mortality; morbidity
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology > MRC Clinical Trials Unit at UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute for Global Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute for Global Health > Infection and Population Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Infection, Immunity and Inflammation Dept
URI: https://discovery.ucl.ac.uk/id/eprint/10040800
Downloads since deposit
59Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item