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, Kara 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

5 Citations (Scopus)

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

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Cryptococcosis
Morbidity
Mortality
Tuberculosis
Africa South of the Sahara
Sulfamethoxazole Drug Combination Trimethoprim
Therapeutics
CD4 Lymphocyte Count
Immunosuppression
Incidence
Infection

Keywords

  • Africa
  • antiretroviral therapy
  • HIV
  • morbidity
  • mortality

ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases

Cite this

Post, F. A., Szubert, A. J., Prendergast, A. J., Johnston, V., Lyall, H., Fitzgerald, F., ... 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

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

In: Clinical Infectious Diseases, Vol. 66, 04.03.2018, p. S132-S139.

Research output: Contribution to journalArticle

Post, FA, Szubert, AJ, Prendergast, AJ, 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, DM, Pett, SL, Kityo, C, Wavamunno, P, Nambi, E, Ocitti, P, Ndigendawani, M, Portal, F, Kabahenda, S, Kemigisa, M, Acen, J, Olebo, D, Mpamize, G, Amone, A, Okweny, D, Mbonye, A, Nambaziira, F, Rweyora, A, Kangah, M, Kabaswahili, V, Abach, J, Abongomera, G, Omongin, J, Aciro, I, Philliam, A, Arach, B, Ocung, E, Amone, G, Miles, P, Adong, C, Tumsuiime, C, Kidega, P, Otto, B, Apio, F, Baleeta, K, Mukuye, A, Abwola, M, Ssennono, F, Baliruno, D, Tuhirwe, S, Namisi, R, Kigongo, F, Kikyonkyo, D, Mushahara, F, Tusiime, J, Musiime, A, Nankya, A, Atwongyeire, D, Sirikye, S, Mula, S, Noowe, N, Lugemwa, A, Kasozi, M, Mwebe, S, Atwine, L, Senkindu, T, Natuhurira, T, Katemba, C, Ninsiima, E, Acaku, M, Kyomuhangi, J, Ankunda, R, Tukwasibwe, D, Ayesiga, L, Nathoo, K, Bwakura-Dangarembizi, M, Reid, A, Chidziva, E, Mhute, T, Tinago, GC, Bhiri, J, Mudzingwa, S, Phiri, M, Steamer, J, Nhema, R, Warambwa, C, Mutsai, S, Nemasango, B, Moyo, C, Chitongo, S, Rashirai, K, Vhembo, S, Mlambo, B, Nkomani, S, Ndemera, B, Willard, M, Berejena, C, Musodza, Y, Matiza, P, Mudenge, B, Guti, V, Etyang, A, Berkley, J, Maitland, K, Njuguna, P, Mwaringa, S, Etyang, T, Awuondo, K, Wale, S, Shangala, J, Kithunga, J, Mwarumba, S, Said Maitha, S, Mutai, R, Lozi Lewa, M, Mwambingu, G, Mwanzu, A, Kalama, C, Latham, H, Shikuku, J, Fondo, A, Njogu, A, Khadenge, C, Mwakisha, B, Siika, A, Wools-Kaloustian, K, Nyandiko, W, Cheruiyot, P, Sudoi, A, Wachira, S, Meli, B, Karoney, M, Nzioka, A, Tanui, M, Mokaya, M, Ekiru, W, Mboya, C, Mwimali, D, Mengich, C, Choge, J, Injera, W, Njenga, K, Cherutich, S, Anyango Orido, M, Omondi Lwande, G, Rutto, P, Mudogo, A, Kutto, I, Shali, A, Jaika, L, Jerotich, H, Pierre, M, Kaunda, S, Van Oosterhout, J, O'Hare, B, Heydermann, R, Gonzalez, C, Dzabala, N, Kelly, C, Denis, B, Selemani, G, Nyondo Mipando, L, Chirwa, E, Banda, P, Mvula, L, Msuku, H, Ziwoya, M, Manda, Y, Nicholas, S, Masesa, C, Mwalukomo, T, Makhaza, L, Sheha, I, Bwanali, J, Limbuni, M, Thomason, M, Griffiths, A, Spyer, M, Klein, N, Rauchenberger, M, Van Looy, N, Little, E, Fairbrother, K, Cowan, F, Seeley, J, Bernays, S, Kawuma, R, Mupambireyi, Z, Kyomuhendo, F, Nakalanzi, S, Peshu, J, Ndaa, S, Chabuka, J, Mkandawire, N, Matandika, L, Kapuya, C, Weller, I, Malianga, E, Mwansambo, C, Miiro, F, Elyanu, P, Bukusi, E, Katabira, E, Mugurungi, O, Peto, T, Musoke, P, Matenga, J, Phiri, S, Ssali, F, Arenas-Pinto, A, Turkova, A & Bamford, A 2018, 'Causes and Timing of Mortality and Morbidity among Late Presenters Starting Antiretroviral Therapy in the REALITY Trial', Clinical Infectious Diseases, vol. 66, pp. S132-S139. https://doi.org/10.1093/cid/cix1141
Post, Frank A. ; Szubert, Alexander J. ; Prendergast, Andrew J. ; Johnston, Victoria ; Lyall, Hermione ; Fitzgerald, Felicity ; Musiime, Victor ; Musoro, Godfrey ; Chepkorir, Priscilla ; Agutu, Clara ; Mallewa, Jane ; Rajapakse, Chathurika ; Wilkes, Helen ; Hakim, James ; Mugyenyi, Peter ; Sarah Walker, A. ; Gibb, Diana M. ; Pett, Sarah L. ; Kityo, C. ; Wavamunno, P. ; Nambi, E. ; Ocitti, P. ; Ndigendawani, M. ; Portal, F. ; Kabahenda, S. ; Kemigisa, M. ; Acen, J. ; Olebo, D. ; Mpamize, G. ; Amone, A. ; Okweny, D. ; Mbonye, A. ; Nambaziira, F. ; Rweyora, A. ; Kangah, M. ; Kabaswahili, V. ; Abach, J. ; Abongomera, G. ; Omongin, J. ; Aciro, I. ; Philliam, A. ; Arach, B. ; Ocung, E. ; Amone, G. ; Miles, P. ; Adong, C. ; Tumsuiime, C. ; Kidega, P. ; Otto, B. ; Apio, F. ; Baleeta, K. ; Mukuye, A. ; Abwola, M. ; Ssennono, F. ; Baliruno, D. ; Tuhirwe, S. ; Namisi, R. ; Kigongo, F. ; Kikyonkyo, D. ; Mushahara, F. ; Tusiime, J. ; Musiime, A. ; Nankya, A. ; Atwongyeire, D. ; Sirikye, S. ; Mula, S. ; Noowe, N. ; Lugemwa, A. ; Kasozi, M. ; Mwebe, S. ; Atwine, L. ; Senkindu, T. ; Natuhurira, T. ; Katemba, C. ; Ninsiima, E. ; Acaku, M. ; Kyomuhangi, J. ; Ankunda, R. ; Tukwasibwe, D. ; Ayesiga, L. ; Nathoo, K. ; Bwakura-Dangarembizi, M. ; Reid, A. ; Chidziva, E. ; Mhute, T. ; Tinago, G. C. ; Bhiri, J. ; Mudzingwa, S. ; Phiri, M. ; Steamer, J. ; Nhema, R. ; Warambwa, C. ; Mutsai, S. ; Nemasango, B. ; Moyo, C. ; Chitongo, S. ; Rashirai, K. ; Vhembo, S. ; Mlambo, B. ; Nkomani, S. ; Ndemera, B. ; Willard, M. ; Berejena, C. ; Musodza, Y. ; Matiza, P. ; Mudenge, B. ; Guti, V. ; Etyang, A. ; Berkley, J. ; Maitland, K. ; Njuguna, P. ; Mwaringa, S. ; Etyang, T. ; Awuondo, K. ; Wale, S. ; Shangala, J. ; Kithunga, J. ; Mwarumba, S. ; Said Maitha, S. ; Mutai, R. ; Lozi Lewa, M. ; Mwambingu, G. ; Mwanzu, A. ; Kalama, C. ; Latham, H. ; Shikuku, J. ; Fondo, A. ; Njogu, A. ; Khadenge, C. ; Mwakisha, B. ; Siika, A. ; Wools-Kaloustian, Kara ; Nyandiko, W. ; Cheruiyot, P. ; Sudoi, A. ; Wachira, S. ; Meli, B. ; Karoney, M. ; Nzioka, A. ; Tanui, M. ; Mokaya, M. ; Ekiru, W. ; Mboya, C. ; Mwimali, D. ; Mengich, C. ; Choge, J. ; Injera, W. ; Njenga, K. ; Cherutich, S. ; Anyango Orido, M. ; Omondi Lwande, G. ; Rutto, P. ; Mudogo, A. ; Kutto, I. ; Shali, A. ; Jaika, L. ; Jerotich, H. ; Pierre, M. ; Kaunda, S. ; Van Oosterhout, J. ; O'Hare, B. ; Heydermann, R. ; Gonzalez, C. ; Dzabala, N. ; Kelly, C. ; Denis, B. ; Selemani, G. ; Nyondo Mipando, L. ; Chirwa, E. ; Banda, P. ; Mvula, L. ; Msuku, H. ; Ziwoya, M. ; Manda, Y. ; Nicholas, S. ; Masesa, C. ; Mwalukomo, T. ; Makhaza, L. ; Sheha, I. ; Bwanali, J. ; Limbuni, M. ; Thomason, M. ; Griffiths, A. ; Spyer, M. ; Klein, N. ; Rauchenberger, M. ; Van Looy, N. ; Little, E. ; Fairbrother, K. ; Cowan, F. ; Seeley, J. ; Bernays, S. ; Kawuma, R. ; Mupambireyi, Z. ; Kyomuhendo, F. ; Nakalanzi, S. ; Peshu, J. ; Ndaa, S. ; Chabuka, J. ; Mkandawire, N. ; Matandika, L. ; Kapuya, C. ; Weller, I. ; Malianga, E. ; Mwansambo, C. ; Miiro, F. ; Elyanu, P. ; Bukusi, E. ; Katabira, E. ; Mugurungi, O. ; Peto, T. ; Musoke, P. ; Matenga, J. ; Phiri, S. ; Ssali, F. ; Arenas-Pinto, A. ; Turkova, A. ; Bamford, A. / Causes and Timing of Mortality and Morbidity among Late Presenters Starting Antiretroviral Therapy in the REALITY Trial. In: Clinical Infectious Diseases. 2018 ; Vol. 66. pp. S132-S139.
@article{29d9435d897f4372a55318eea91a025f,
title = "Causes and Timing of Mortality and Morbidity among Late Presenters Starting Antiretroviral Therapy in the REALITY Trial",
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.",
keywords = "Africa, antiretroviral therapy, HIV, morbidity, mortality",
author = "Post, {Frank A.} and Szubert, {Alexander J.} and Prendergast, {Andrew J.} and Victoria Johnston and Hermione Lyall and Felicity Fitzgerald and Victor Musiime and Godfrey Musoro and Priscilla Chepkorir and Clara Agutu and Jane Mallewa and Chathurika Rajapakse and Helen Wilkes and James Hakim and Peter Mugyenyi and {Sarah Walker}, A. and Gibb, {Diana M.} and Pett, {Sarah L.} and C. Kityo and P. Wavamunno and E. Nambi and P. Ocitti and M. Ndigendawani and F. Portal and S. Kabahenda and M. Kemigisa and J. Acen and D. Olebo and G. Mpamize and A. Amone and D. Okweny and A. Mbonye and F. Nambaziira and A. Rweyora and M. Kangah and V. Kabaswahili and J. Abach and G. Abongomera and J. Omongin and I. Aciro and A. Philliam and B. Arach and E. Ocung and G. Amone and P. Miles and C. Adong and C. Tumsuiime and P. Kidega and B. Otto and F. Apio and K. Baleeta and A. Mukuye and M. Abwola and F. Ssennono and D. Baliruno and S. Tuhirwe and R. Namisi and F. Kigongo and D. Kikyonkyo and F. Mushahara and J. Tusiime and A. Musiime and A. Nankya and D. Atwongyeire and S. Sirikye and S. Mula and N. Noowe and A. Lugemwa and M. Kasozi and S. Mwebe and L. Atwine and T. Senkindu and T. Natuhurira and C. Katemba and E. Ninsiima and M. Acaku and J. Kyomuhangi and R. Ankunda and D. Tukwasibwe and L. Ayesiga and K. Nathoo and M. Bwakura-Dangarembizi and A. Reid and E. Chidziva and T. Mhute and Tinago, {G. C.} and J. Bhiri and S. Mudzingwa and M. Phiri and J. Steamer and R. Nhema and C. Warambwa and S. Mutsai and B. Nemasango and C. Moyo and S. Chitongo and K. Rashirai and S. Vhembo and B. Mlambo and S. Nkomani and B. Ndemera and M. Willard and C. Berejena and Y. Musodza and P. Matiza and B. Mudenge and V. Guti and A. Etyang and J. Berkley and K. Maitland and P. Njuguna and S. Mwaringa and T. Etyang and K. Awuondo and S. Wale and J. Shangala and J. Kithunga and S. Mwarumba and {Said Maitha}, S. and R. Mutai and {Lozi Lewa}, M. and G. Mwambingu and A. Mwanzu and C. Kalama and H. Latham and J. Shikuku and A. Fondo and A. Njogu and C. Khadenge and B. Mwakisha and A. Siika and Kara Wools-Kaloustian and W. Nyandiko and P. Cheruiyot and A. Sudoi and S. Wachira and B. Meli and M. Karoney and A. Nzioka and M. Tanui and M. Mokaya and W. Ekiru and C. Mboya and D. Mwimali and C. Mengich and J. Choge and W. Injera and K. Njenga and S. Cherutich and {Anyango Orido}, M. and {Omondi Lwande}, G. and P. Rutto and A. Mudogo and I. Kutto and A. Shali and L. Jaika and H. Jerotich and M. Pierre and S. Kaunda and {Van Oosterhout}, J. and B. O'Hare and R. Heydermann and C. Gonzalez and N. Dzabala and C. Kelly and B. Denis and G. Selemani and {Nyondo Mipando}, L. and E. Chirwa and P. Banda and L. Mvula and H. Msuku and M. Ziwoya and Y. Manda and S. Nicholas and C. Masesa and T. Mwalukomo and L. Makhaza and I. Sheha and J. Bwanali and M. Limbuni and M. Thomason and A. Griffiths and M. Spyer and N. Klein and M. Rauchenberger and {Van Looy}, N. and E. Little and K. Fairbrother and F. Cowan and J. Seeley and S. Bernays and R. Kawuma and Z. Mupambireyi and F. Kyomuhendo and S. Nakalanzi and J. Peshu and S. Ndaa and J. Chabuka and N. Mkandawire and L. Matandika and C. Kapuya and I. Weller and E. Malianga and C. Mwansambo and F. Miiro and P. Elyanu and E. Bukusi and E. Katabira and O. Mugurungi and T. Peto and P. Musoke and J. Matenga and S. Phiri and F. Ssali and A. Arenas-Pinto and A. Turkova and A. Bamford",
year = "2018",
month = "3",
day = "4",
doi = "10.1093/cid/cix1141",
language = "English (US)",
volume = "66",
pages = "S132--S139",
journal = "Clinical Infectious Diseases",
issn = "1058-4838",
publisher = "Oxford University Press",

}

TY - JOUR

T1 - Causes and Timing of Mortality and Morbidity among Late Presenters Starting Antiretroviral Therapy in the REALITY Trial

AU - Post, Frank A.

AU - Szubert, Alexander J.

AU - Prendergast, Andrew J.

AU - Johnston, Victoria

AU - Lyall, Hermione

AU - Fitzgerald, Felicity

AU - Musiime, Victor

AU - Musoro, Godfrey

AU - Chepkorir, Priscilla

AU - Agutu, Clara

AU - Mallewa, Jane

AU - Rajapakse, Chathurika

AU - Wilkes, Helen

AU - Hakim, James

AU - Mugyenyi, Peter

AU - Sarah Walker, A.

AU - Gibb, Diana M.

AU - Pett, Sarah L.

AU - Kityo, C.

AU - Wavamunno, P.

AU - Nambi, E.

AU - Ocitti, P.

AU - Ndigendawani, M.

AU - Portal, F.

AU - Kabahenda, S.

AU - Kemigisa, M.

AU - Acen, J.

AU - Olebo, D.

AU - Mpamize, G.

AU - Amone, A.

AU - Okweny, D.

AU - Mbonye, A.

AU - Nambaziira, F.

AU - Rweyora, A.

AU - Kangah, M.

AU - Kabaswahili, V.

AU - Abach, J.

AU - Abongomera, G.

AU - Omongin, J.

AU - Aciro, I.

AU - Philliam, A.

AU - Arach, B.

AU - Ocung, E.

AU - Amone, G.

AU - Miles, P.

AU - Adong, C.

AU - Tumsuiime, C.

AU - Kidega, P.

AU - Otto, B.

AU - Apio, F.

AU - Baleeta, K.

AU - Mukuye, A.

AU - Abwola, M.

AU - Ssennono, F.

AU - Baliruno, D.

AU - Tuhirwe, S.

AU - Namisi, R.

AU - Kigongo, F.

AU - Kikyonkyo, D.

AU - Mushahara, F.

AU - Tusiime, J.

AU - Musiime, A.

AU - Nankya, A.

AU - Atwongyeire, D.

AU - Sirikye, S.

AU - Mula, S.

AU - Noowe, N.

AU - Lugemwa, A.

AU - Kasozi, M.

AU - Mwebe, S.

AU - Atwine, L.

AU - Senkindu, T.

AU - Natuhurira, T.

AU - Katemba, C.

AU - Ninsiima, E.

AU - Acaku, M.

AU - Kyomuhangi, J.

AU - Ankunda, R.

AU - Tukwasibwe, D.

AU - Ayesiga, L.

AU - Nathoo, K.

AU - Bwakura-Dangarembizi, M.

AU - Reid, A.

AU - Chidziva, E.

AU - Mhute, T.

AU - Tinago, G. C.

AU - Bhiri, J.

AU - Mudzingwa, S.

AU - Phiri, M.

AU - Steamer, J.

AU - Nhema, R.

AU - Warambwa, C.

AU - Mutsai, S.

AU - Nemasango, B.

AU - Moyo, C.

AU - Chitongo, S.

AU - Rashirai, K.

AU - Vhembo, S.

AU - Mlambo, B.

AU - Nkomani, S.

AU - Ndemera, B.

AU - Willard, M.

AU - Berejena, C.

AU - Musodza, Y.

AU - Matiza, P.

AU - Mudenge, B.

AU - Guti, V.

AU - Etyang, A.

AU - Berkley, J.

AU - Maitland, K.

AU - Njuguna, P.

AU - Mwaringa, S.

AU - Etyang, T.

AU - Awuondo, K.

AU - Wale, S.

AU - Shangala, J.

AU - Kithunga, J.

AU - Mwarumba, S.

AU - Said Maitha, S.

AU - Mutai, R.

AU - Lozi Lewa, M.

AU - Mwambingu, G.

AU - Mwanzu, A.

AU - Kalama, C.

AU - Latham, H.

AU - Shikuku, J.

AU - Fondo, A.

AU - Njogu, A.

AU - Khadenge, C.

AU - Mwakisha, B.

AU - Siika, A.

AU - Wools-Kaloustian, Kara

AU - Nyandiko, W.

AU - Cheruiyot, P.

AU - Sudoi, A.

AU - Wachira, S.

AU - Meli, B.

AU - Karoney, M.

AU - Nzioka, A.

AU - Tanui, M.

AU - Mokaya, M.

AU - Ekiru, W.

AU - Mboya, C.

AU - Mwimali, D.

AU - Mengich, C.

AU - Choge, J.

AU - Injera, W.

AU - Njenga, K.

AU - Cherutich, S.

AU - Anyango Orido, M.

AU - Omondi Lwande, G.

AU - Rutto, P.

AU - Mudogo, A.

AU - Kutto, I.

AU - Shali, A.

AU - Jaika, L.

AU - Jerotich, H.

AU - Pierre, M.

AU - Kaunda, S.

AU - Van Oosterhout, J.

AU - O'Hare, B.

AU - Heydermann, R.

AU - Gonzalez, C.

AU - Dzabala, N.

AU - Kelly, C.

AU - Denis, B.

AU - Selemani, G.

AU - Nyondo Mipando, L.

AU - Chirwa, E.

AU - Banda, P.

AU - Mvula, L.

AU - Msuku, H.

AU - Ziwoya, M.

AU - Manda, Y.

AU - Nicholas, S.

AU - Masesa, C.

AU - Mwalukomo, T.

AU - Makhaza, L.

AU - Sheha, I.

AU - Bwanali, J.

AU - Limbuni, M.

AU - Thomason, M.

AU - Griffiths, A.

AU - Spyer, M.

AU - Klein, N.

AU - Rauchenberger, M.

AU - Van Looy, N.

AU - Little, E.

AU - Fairbrother, K.

AU - Cowan, F.

AU - Seeley, J.

AU - Bernays, S.

AU - Kawuma, R.

AU - Mupambireyi, Z.

AU - Kyomuhendo, F.

AU - Nakalanzi, S.

AU - Peshu, J.

AU - Ndaa, S.

AU - Chabuka, J.

AU - Mkandawire, N.

AU - Matandika, L.

AU - Kapuya, C.

AU - Weller, I.

AU - Malianga, E.

AU - Mwansambo, C.

AU - Miiro, F.

AU - Elyanu, P.

AU - Bukusi, E.

AU - Katabira, E.

AU - Mugurungi, O.

AU - Peto, T.

AU - Musoke, P.

AU - Matenga, J.

AU - Phiri, S.

AU - Ssali, F.

AU - Arenas-Pinto, A.

AU - Turkova, A.

AU - Bamford, A.

PY - 2018/3/4

Y1 - 2018/3/4

N2 - 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.

AB - 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.

KW - Africa

KW - antiretroviral therapy

KW - HIV

KW - morbidity

KW - mortality

UR - http://www.scopus.com/inward/record.url?scp=85043356437&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85043356437&partnerID=8YFLogxK

U2 - 10.1093/cid/cix1141

DO - 10.1093/cid/cix1141

M3 - Article

C2 - 29514234

AN - SCOPUS:85043356437

VL - 66

SP - S132-S139

JO - Clinical Infectious Diseases

JF - Clinical Infectious Diseases

SN - 1058-4838

ER -