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

Frank A. Post(King's College Hospital NHS Foundation Trust), Alexander J. Szubert(University College London), Andrew J. Prendergast(Queen Mary University of London), Victoria Johnston(London School of Hygiene & Tropical Medicine), Hermione Lyall(Imperial College Healthcare NHS Trust), Felicity Fitzgerald(Great Ormond Street Hospital), Victor Musiime(Joint Clinical Research Centre), Godfrey Musoro(University of Zimbabwe), Priscilla Chepkorir(Moi University), Clara Agutu(Kenya Medical Research Institute), Jane Mallewa(University of Liverpool), C Rajapakse(University College London), Helen Wilkes(University College London), James Hakim(University of Zimbabwe), Peter Mugyenyi(Joint Clinical Research Centre), A. Sarah Walker(University College London), Diana M. Gibb(University College London), Sarah Pett(UNSW Sydney), Reduction of EArly mortaLITY in HIV-infected adults and children starting antiretroviral therapy (REALITY) Trial Team(University College London), Diana M. Gibb(University College London), Margaret J. Thomason(University College London), A. Sarah Walker(UNSW Sydney), Sarah Pett(UNSW Sydney), Alexander J. Szubert(University College London), Anna Griffiths(University College London), H Wilkes(University College London), C Rajapakse(University College London), Moira Spyer(Queen Mary University of London), Andrew J. Prendergast(Queen Mary University of London), Nigel Klein, Nadine Van Looy, Emma Little(University College London), Keith Fairbrother, Frances M. Cowan(University of Zimbabwe), Janet Seeley, Sarah Bernays, Rachel Kawuma(Great Ormond Street Hospital), Zivai Mupambireyi, F Kyomuhendo, S Nakalanzi(University of Zimbabwe), J Peshu, S Ndaa(University of Zimbabwe), J Chabuka, NC Mkandawire, L Matandika, C Kapuya, Ian Weller, E Malianga, Charles Mwansambo, F Miiro, P Elyanu, Elizabeth A. Bukusi, Elly Katabira, Owen Mugurungi(University College London), Diana M. Gibb(University of Zimbabwe), James Hakim(University of Zimbabwe), Anthony Etyang(Joint Clinical Research Centre), Peter Mugyenyi(University of Liverpool), Jane Mallewa(University of Liverpool), Tünde Pető, Philippa Musoke(University of Zimbabwe), Jonathan Matenga, Sam Phiri(Imperial College Healthcare NHS Trust), Hermione Lyall(Imperial College Healthcare NHS Trust), Victoria Johnston(Great Ormond Street Hospital), Felicity Fitzgerald(Great Ormond Street Hospital), Frank A. Post(King's College Hospital NHS Foundation Trust), Francis Ssali(Queen Mary University of London), Andrew J. Prendergast(Queen Mary University of London), Alejandro Arenas‐Pinto, Anna Turkova, Alasdair Bamford
Clinical Infectious Diseases
January 2, 2018
10.1093/cid/cix1141
Cited by 42Open Access
Full Text

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 azithromycin-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-responsive 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. Clinical Trials Registration: ISRCTN43622374.

Related Papers

No related papers found

Powered by citation graph analysis