Causes and timing of mortality and morbidity among late presenters starting antiretroviral therapy in the REALITY trial
<p>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,...
| Main Authors: | , , , , , , , , , , , , , , , , , , |
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| Format: | Journal article |
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Oxford University Press
2018
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| _version_ | 1826288739433840640 |
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| author | Post, F Szubert, A Prendergast, A Johnston, V Lyall, H Fitzgerald, F Musiime, V Musoro, G Chepkrorir, P Agutu, C Mallewa, J Rajapakse, C Wilkes, H Hakim, J Mugyenyi, P Walker, A Gibb, D Pett, S on behalf of the REALITY trial team |
| author_facet | Post, F Szubert, A Prendergast, A Johnston, V Lyall, H Fitzgerald, F Musiime, V Musoro, G Chepkrorir, P Agutu, C Mallewa, J Rajapakse, C Wilkes, H Hakim, J Mugyenyi, P Walker, A Gibb, D Pett, S on behalf of the REALITY trial team |
| author_sort | Post, F |
| collection | OXFORD |
| description | <p>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.</p><p> 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).</p><p> 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.</p><p> 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. </p> |
| first_indexed | 2024-03-07T02:18:15Z |
| format | Journal article |
| id | oxford-uuid:a303eed7-be79-43e9-861a-47a3ac82d098 |
| institution | University of Oxford |
| last_indexed | 2024-03-07T02:18:15Z |
| publishDate | 2018 |
| publisher | Oxford University Press |
| record_format | dspace |
| spelling | oxford-uuid:a303eed7-be79-43e9-861a-47a3ac82d0982022-03-27T02:23:54ZCauses and timing of mortality and morbidity among late presenters starting antiretroviral therapy in the REALITY trialJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:a303eed7-be79-43e9-861a-47a3ac82d098Symplectic Elements at OxfordOxford University Press2018Post, FSzubert, APrendergast, AJohnston, VLyall, HFitzgerald, FMusiime, VMusoro, GChepkrorir, PAgutu, CMallewa, JRajapakse, CWilkes, HHakim, JMugyenyi, PWalker, AGibb, DPett, Son behalf of the REALITY trial team<p>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.</p><p> 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).</p><p> 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.</p><p> 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. </p> |
| spellingShingle | Post, F Szubert, A Prendergast, A Johnston, V Lyall, H Fitzgerald, F Musiime, V Musoro, G Chepkrorir, P Agutu, C Mallewa, J Rajapakse, C Wilkes, H Hakim, J Mugyenyi, P Walker, A Gibb, D Pett, S on behalf of the REALITY trial team Causes and timing of mortality and morbidity among late presenters starting antiretroviral therapy in the REALITY trial |
| title | Causes and timing of mortality and morbidity among late presenters starting antiretroviral therapy in the REALITY trial |
| title_full | Causes and timing of mortality and morbidity among late presenters starting antiretroviral therapy in the REALITY trial |
| title_fullStr | Causes and timing of mortality and morbidity among late presenters starting antiretroviral therapy in the REALITY trial |
| title_full_unstemmed | Causes and timing of mortality and morbidity among late presenters starting antiretroviral therapy in the REALITY trial |
| title_short | Causes and timing of mortality and morbidity among late presenters starting antiretroviral therapy in the REALITY trial |
| title_sort | causes and timing of mortality and morbidity among late presenters starting antiretroviral therapy in the reality trial |
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