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http://ir.mu.ac.ke:8080/jspui/handle/123456789/7885
Title: | Causes and timing of mortality and morbidity among late presenters starting Antiretroviral therapy in the REALITY Trial |
Authors: | Post, Frank A. Szubert, Alexander J. Prendergast, Andrew J. Johnston, Victoria Lyall, Hermione Fitzgerald, Felicity Musoro, Godfrey Musiime, Victor Chepkorir, Priscilla Agutu, Clara Mallewa, Jane Rajapakse, Chathurika Wilkes, Helen Hakim, James Mugyenyi, Peter Walker, Sarah Gibb, Diana M. Pett, Sarah L. |
Keywords: | HIV Antiretroviral therapy Mortality Morbidity |
Issue Date: | 2018 |
Publisher: | Oxford University Press |
Abstract: | Background. In sub-Saharan Africa, 20%–25% of people starting antiretroviral therapy (ART) have severe immunosuppression; approximately 10% die within 3 months. In the Reduction of EArly mortaLITY (REALITY) randomized trial, a broad enhanced anti-infection prophylaxis bundle reduced mortality vs cotrimoxazole. We investigate the contribution and timing of different causes of mortality/morbidity. Methods. Participants started ART with a CD4 count <100 cells/μL; enhanced prophylaxis comprised cotrimoxazole plus 12 weeks of isoniazid + fluconazole, single-dose albendazole, and 5 days of azithromycin. A blinded committee adjudicated events and causes of death as (non–mutually exclusively) tuberculosis, cryptococcosis, severe bacterial infection (SBI), other potentially azith- romycin-responsive infections, other events, and unknown. Results. Median pre-ART CD4 count was 37 cells/μL. Among 1805 participants, 225 (12.7%) died by week 48. Fatal/nonfatal events occurred early (median 4 weeks); rates then declined exponentially. One hundred fifty-four deaths had single and 71 had multiple causes, including tuberculosis in 4.5% participants, cryptococcosis in 1.1%, SBI in 1.9%, other potentially azithromycin-re- sponsive infections in 1.3%, other events in 3.6%, and unknown in 5.0%. Enhanced prophylaxis reduced deaths from cryptococcosis and unknown causes (P < .05) but not tuberculosis, SBI, potentially azithromycin-responsive infections, or other causes (P > .3); and reduced nonfatal/fatal tuberculosis and cryptococcosis (P < .05), but not SBI, other potentially azithromycin-responsive infections, or other events (P > .2). Conclusions. Enhanced prophylaxis reduced mortality from cryptococcosis and unknown causes and nonfatal tuberculosis and cryptococcosis. High early incidence of fatal/nonfatal events highlights the need for starting enhanced-prophylaxis with ART in advanced disease. |
URI: | http://ir.mu.ac.ke:8080/jspui/handle/123456789/7885 |
Appears in Collections: | School of Medicine |
Files in This Item:
File | Description | Size | Format | |
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CHEPKORIR.pdf | 548 kB | Adobe PDF | View/Open |
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