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

Frank A. Post, Alexander J. Szubert, Andrew J. Prendergast, Victoria Johnston, Hermione Lyall, Felicity Fitzgerald, Victor Musiime, Godfrey Musoro, Priscilla Chepkorir, Clara Agutu, Jane Mallewa, Chathurika Rajapakse, Helen Wilkes, James Hakim, Peter Mugyenyi, A. Sarah Walker, Diana M. Gibb, Sarah L. Pett, C. Kityo, P. WavamunnoE. Nambi, P. Ocitti, M. Ndigendawani, F. Portal, S. Kabahenda, M. Kemigisa, J. Acen, D. Olebo, G. Mpamize, A. Amone, D. Okweny, A. Mbonye, F. Nambaziira, A. Rweyora, M. Kangah, V. Kabaswahili, J. Abach, G. Abongomera, J. Omongin, I. Aciro, A. Philliam, B. Arach, E. Ocung, G. Amone, P. Miles, C. Adong, C. Tumsuiime, P. Kidega, B. Otto, F. Apio, K. Baleeta, A. Mukuye, M. Abwola, F. Ssennono, D. Baliruno, S. Tuhirwe, R. Namisi, F. Kigongo, D. Kikyonkyo, F. Mushahara, J. Tusiime, A. Musiime, A. Nankya, D. Atwongyeire, S. Sirikye, S. Mula, N. Noowe, A. Lugemwa, M. Kasozi, S. Mwebe, L. Atwine, T. Senkindu, T. Natuhurira, C. Katemba, E. Ninsiima, M. Acaku, J. Kyomuhangi, R. Ankunda, D. Tukwasibwe, L. Ayesiga, K. Nathoo, M. Bwakura-Dangarembizi, A. Reid, E. Chidziva, T. Mhute, G. C. Tinago, J. Bhiri, S. Mudzingwa, M. Phiri, J. Steamer, R. Nhema, C. Warambwa, S. Mutsai, B. Nemasango, C. Moyo, S. Chitongo, K. Rashirai, S. Vhembo, B. Mlambo, S. Nkomani, B. Ndemera, M. Willard, C. Berejena, Y. Musodza, P. Matiza, B. Mudenge, V. Guti, A. Etyang, J. Berkley, K. Maitland, P. Njuguna, S. Mwaringa, T. Etyang, K. Awuondo, S. Wale, J. Shangala, J. Kithunga, S. Mwarumba, S. Said Maitha, R. Mutai, M. Lozi Lewa, G. Mwambingu, A. Mwanzu, C. Kalama, H. Latham, J. Shikuku, A. Fondo, A. Njogu, C. Khadenge, B. Mwakisha, A. Siika, K. Wools-Kaloustian, W. Nyandiko, P. Cheruiyot, A. Sudoi, S. Wachira, B. Meli, M. Karoney, A. Nzioka, M. Tanui, M. Mokaya, W. Ekiru, C. Mboya, D. Mwimali, C. Mengich, J. Choge, W. Injera, K. Njenga, S. Cherutich, M. Anyango Orido, G. Omondi Lwande, P. Rutto, A. Mudogo, I. Kutto, A. Shali, L. Jaika, H. Jerotich, M. Pierre, S. Kaunda, J. Van Oosterhout, B. O'Hare, R. Heydermann, C. Gonzalez, N. Dzabala, C. Kelly, B. Denis, G. Selemani, L. Nyondo Mipando, E. Chirwa, P. Banda, L. Mvula, H. Msuku, M. Ziwoya, Y. Manda, S. Nicholas, C. Masesa, T. Mwalukomo, L. Makhaza, I. Sheha, J. Bwanali, M. Limbuni, M. Thomason, A. Griffiths, M. Spyer, N. Klein, M. Rauchenberger, N. Van Looy, E. Little, K. Fairbrother, F. Cowan, J. Seeley, S. Bernays, R. Kawuma, Z. Mupambireyi, F. Kyomuhendo, S. Nakalanzi, J. Peshu, S. Ndaa, J. Chabuka, N. Mkandawire, L. Matandika, C. Kapuya, I. Weller, E. Malianga, C. Mwansambo, F. Miiro, P. Elyanu, E. Bukusi, E. Katabira, O. Mugurungi, T. Peto, P. Musoke, J. Matenga, S. Phiri, F. Ssali, A. Arenas-Pinto, A. Turkova, A. Bamford

Research output: Contribution to journalArticle

11 Scopus citations

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 ffy-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.

Original languageEnglish (US)
Pages (from-to)S132-S139
JournalClinical Infectious Diseases
Volume66
DOIs
StatePublished - Mar 4 2018

Keywords

  • Africa
  • HIV
  • antiretroviral therapy
  • morbidity
  • mortality

ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases

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    Post, F. A., Szubert, A. J., Prendergast, A. J., Johnston, V., Lyall, H., Fitzgerald, F., Musiime, V., Musoro, G., Chepkorir, P., Agutu, C., Mallewa, J., Rajapakse, C., Wilkes, H., Hakim, J., Mugyenyi, P., Sarah Walker, A., Gibb, D. M., Pett, S. L., Kityo, C., ... Bamford, A. (2018). Causes and Timing of Mortality and Morbidity among Late Presenters Starting Antiretroviral Therapy in the REALITY Trial. Clinical Infectious Diseases, 66, S132-S139. https://doi.org/10.1093/cid/cix1141