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Published in: BMC Infectious Diseases 1/2019

Open Access 01-12-2019 | Tuberculosis | Research article

A decade of antiretroviral therapy in Uganda: what are the emerging causes of death?

Authors: Agnes N. Kiragga, Frank Mubiru, Andrew D. Kambugu, Moses R. Kamya, Barbara Castelnuovo

Published in: BMC Infectious Diseases | Issue 1/2019

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Abstract

Background

The roll out of antiretroviral therapy (ART) in Sub-Saharan Africa led to a decrease in mortality. Few studies have documented the causes of deaths among patients on long term antiretroviral therapy in Sub-Saharan Africa. Our objective was to describe the causes of death among patients on long term ART in Sub-Saharan Africa.

Methods

We used data from a prospective cohort of ART naïve patients receiving care and treatment at the Infectious Diseases Institute in Kampala, Uganda. Patients were followed up for 10 years. All deaths were recorded and possible causes established using verbal autopsy. Deaths were grouped as HIV-related (ART toxicities, any opportunistic infections (OIs) and HIV-related malignancies) and non-HIV related deaths while some remained unknown. We used Kaplan Meier survival methods to estimate cumulative incidence and rates of mortality for all causes of death.

Results

Of the 559, (386, 69%) were female, median age 36 years (IQR: 21–44), 89% had WHO clinical stages 3 and 4, and median CD4 count at ART initiation was 98 cells/μL (IQR: 21–163). A total of 127 (22.7%) deaths occurred in 10 years. The HIV related causes of death (n = 70) included the following; Tuberculosis 17 (24.3%), Cryptococcal meningitis 10 (15.7%), Kaposi’s Sarcoma 7(10%), HIV related toxicity 6 (8.6%), HIV related anemia 5(7.1%), Pneumocystis carinii Pneumonia (PCP) 5 (7.1%), HIV related chronic diarrhea 4 (5.7%), Non-Hodgkin Lymphoma 3 (4.3%), Herpes Zoster 2 (2.8%), other 10 (14.3%). The non-HIV related causes of death (n = 20) included non-communicable diseases (diabetes, hypertension, stroke) 6 (30%), malaria 3 (15%), pregnancy-related death 2 (10%), cervical cancer 2 (10%), trauma 1(5%) and others 6 (30%).

Conclusion

Despite the higher rates of deaths from OIs in the early years of ART initiation, we observed an emergence of non-HIV related causes of morbidity and mortality. It is recommended that HIV programs in resource-limited settings start planning for screening and treatment of non-communicable diseases.
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Literature
1.
go back to reference Larson E, et al. Population-level associations between antiretroviral therapy scale-up and all-cause mortality in South Africa. Int J STD AIDS. 2014;25(9):636–42.CrossRef Larson E, et al. Population-level associations between antiretroviral therapy scale-up and all-cause mortality in South Africa. Int J STD AIDS. 2014;25(9):636–42.CrossRef
2.
go back to reference UNAIDS. Fact Sheet - Latest statistics on the status of the AIDS epidemic. 2017 [cited 2017 24th July ]. UNAIDS. Fact Sheet - Latest statistics on the status of the AIDS epidemic. 2017 [cited 2017 24th July ].
3.
4.
go back to reference Antiretroviral Therapy Cohort C. Survival of HIV-positive patients starting antiretroviral therapy between 1996 and 2013: a collaborative analysis of cohort studies. Lancet HIV. 2017;4(8):e349–56.CrossRef Antiretroviral Therapy Cohort C. Survival of HIV-positive patients starting antiretroviral therapy between 1996 and 2013: a collaborative analysis of cohort studies. Lancet HIV. 2017;4(8):e349–56.CrossRef
5.
go back to reference Commission, M.o.H.N.A. Treatment of AIDS Guidelines for the Ise of Antiretroviral Therapy in Malawi. Lilongwe; 2003. Commission, M.o.H.N.A. Treatment of AIDS Guidelines for the Ise of Antiretroviral Therapy in Malawi. Lilongwe; 2003.
6.
go back to reference Harries AD, Schouten EJ, Libamba E. Scaling up antiretroviral treatment in resource-poor settings. Lancet. 2006;367(9525):1870–2.CrossRef Harries AD, Schouten EJ, Libamba E. Scaling up antiretroviral treatment in resource-poor settings. Lancet. 2006;367(9525):1870–2.CrossRef
7.
go back to reference Ministry of Health Uganda. Uganda National Antiretroviral Treatment and Care Guidelines for Adults, Adolescents and Children. Released 2003. Ministry of Health Uganda. Uganda National Antiretroviral Treatment and Care Guidelines for Adults, Adolescents and Children. Released 2003.
8.
go back to reference Braitstein P, et al. Mortality of HIV-1-infected patients in the first year of antiretroviral therapy: comparison between low-income and high-income countries. Lancet. 2006;367(9513):817–24.CrossRef Braitstein P, et al. Mortality of HIV-1-infected patients in the first year of antiretroviral therapy: comparison between low-income and high-income countries. Lancet. 2006;367(9513):817–24.CrossRef
9.
go back to reference Global. Regional, and national age-sex specific mortality for 264 causes of death, 1980–2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet. 2017;390(10100):1151–210.CrossRef Global. Regional, and national age-sex specific mortality for 264 causes of death, 1980–2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet. 2017;390(10100):1151–210.CrossRef
10.
go back to reference Castelnuovo B, et al. Cause-specific mortality and the contribution of immune reconstitution inflammatory syndrome in the first 3 years after antiretroviral therapy initiation in an urban African cohort. Clin Infect Dis. 2009;49(6):965–72.CrossRef Castelnuovo B, et al. Cause-specific mortality and the contribution of immune reconstitution inflammatory syndrome in the first 3 years after antiretroviral therapy initiation in an urban African cohort. Clin Infect Dis. 2009;49(6):965–72.CrossRef
11.
go back to reference Nwaka S, et al. Analysis of pan-African Centres of excellence in health innovation highlights opportunities and challenges for local innovation and financing in the continent. BMC Int Health Hum Rights. 2012;12:11.CrossRef Nwaka S, et al. Analysis of pan-African Centres of excellence in health innovation highlights opportunities and challenges for local innovation and financing in the continent. BMC Int Health Hum Rights. 2012;12:11.CrossRef
12.
go back to reference Kamya MR, et al. Predictors of long-term viral failure among ugandan children and adults treated with antiretroviral therapy. J Acquir Immune Defic Syndr. 2007;46(2):187–93.CrossRef Kamya MR, et al. Predictors of long-term viral failure among ugandan children and adults treated with antiretroviral therapy. J Acquir Immune Defic Syndr. 2007;46(2):187–93.CrossRef
13.
go back to reference Castelnuovo B, et al. Outcomes in a Cohort of patients started on Antiretroviral treatment and followed up for a decade in an Urban Clinic in Uganda. PLoS One. 2015;10(12):e0142722.CrossRef Castelnuovo B, et al. Outcomes in a Cohort of patients started on Antiretroviral treatment and followed up for a decade in an Urban Clinic in Uganda. PLoS One. 2015;10(12):e0142722.CrossRef
14.
go back to reference WHO, Scaling up antiretroviral therapy in resource-limited settings: Treatment guidelines for a public health approach. 2013. WHO, Scaling up antiretroviral therapy in resource-limited settings: Treatment guidelines for a public health approach. 2013.
15.
go back to reference Global Trends in CD4 Cell Count at the Start of Antiretroviral Therapy. Collaborative study of treatment programs. Clin Infect Dis. 2018;66(6):893–903.CrossRef Global Trends in CD4 Cell Count at the Start of Antiretroviral Therapy. Collaborative study of treatment programs. Clin Infect Dis. 2018;66(6):893–903.CrossRef
16.
go back to reference Saavedra A, et al. Causes of death and factors associated with early mortality of HIV-infected adults admitted to Korle-Bu teaching hospital. Pan Afr Med J. 2017;27:48.CrossRef Saavedra A, et al. Causes of death and factors associated with early mortality of HIV-infected adults admitted to Korle-Bu teaching hospital. Pan Afr Med J. 2017;27:48.CrossRef
17.
go back to reference French AL, et al. Trends in mortality and causes of death among women with HIV in the United States: a 10-year study. J Acquir Immune Defic Syndr. 2009;51(4):399–406.CrossRef French AL, et al. Trends in mortality and causes of death among women with HIV in the United States: a 10-year study. J Acquir Immune Defic Syndr. 2009;51(4):399–406.CrossRef
18.
go back to reference Groenewald P, et al. Mortality trends in the City of Cape Town between 2001 and 2013: reducing inequities in health. S Afr Med J. 2017;107(12):1091–8.CrossRef Groenewald P, et al. Mortality trends in the City of Cape Town between 2001 and 2013: reducing inequities in health. S Afr Med J. 2017;107(12):1091–8.CrossRef
19.
go back to reference Misganaw A, et al. National mortality burden due to communicable, non-communicable, and other diseases in Ethiopia, 1990-2015: findings from the global burden of disease study 2015. Popul Health Metrics. 2017;15(1):29.CrossRef Misganaw A, et al. National mortality burden due to communicable, non-communicable, and other diseases in Ethiopia, 1990-2015: findings from the global burden of disease study 2015. Popul Health Metrics. 2017;15(1):29.CrossRef
20.
go back to reference Gamboa-Acuna B, et al. Factors associated to survival in patients with HIV-TB in the Department of Infectious Diseases of the Arzobispo Loayza National Hospital, Peru, since 2004 to 2012. Rev Chil Infectol. 2018;35(1):41–8.CrossRef Gamboa-Acuna B, et al. Factors associated to survival in patients with HIV-TB in the Department of Infectious Diseases of the Arzobispo Loayza National Hospital, Peru, since 2004 to 2012. Rev Chil Infectol. 2018;35(1):41–8.CrossRef
21.
go back to reference Hamusse SD, et al. Fifteen-year trend in treatment outcomes among patients with pulmonary smear-positive tuberculosis and its determinants in Arsi zone, Central Ethiopia. Glob Health Action. 2014;7:25382.CrossRef Hamusse SD, et al. Fifteen-year trend in treatment outcomes among patients with pulmonary smear-positive tuberculosis and its determinants in Arsi zone, Central Ethiopia. Glob Health Action. 2014;7:25382.CrossRef
22.
go back to reference Onyango DO, et al. Reduction of HIV-associated excess mortality by antiretroviral treatment among tuberculosis patients in Kenya, e0188235. PLoS One. 2017;12(11). Onyango DO, et al. Reduction of HIV-associated excess mortality by antiretroviral treatment among tuberculosis patients in Kenya, e0188235. PLoS One. 2017;12(11).
23.
go back to reference Post FA, et al. Causes and timing of mortality and morbidity among late presenters starting Antiretroviral Therapy in the REALITY trial. Clin Infect Dis. 2018;66(suppl_2):S132–9.CrossRef Post FA, et al. Causes and timing of mortality and morbidity among late presenters starting Antiretroviral Therapy in the REALITY trial. Clin Infect Dis. 2018;66(suppl_2):S132–9.CrossRef
24.
go back to reference Lawn SD, et al. Early mortality among adults accessing antiretroviral treatment programmes in sub-Saharan Africa. AIDS. 2008;22(15):1897–908.CrossRef Lawn SD, et al. Early mortality among adults accessing antiretroviral treatment programmes in sub-Saharan Africa. AIDS. 2008;22(15):1897–908.CrossRef
25.
go back to reference Mermin J, et al. Utility of routine viral load, CD4 cell count, and clinical monitoring among adults with HIV receiving antiretroviral therapy in Uganda: randomised trial. BMJ. 2011;343:d6792.CrossRef Mermin J, et al. Utility of routine viral load, CD4 cell count, and clinical monitoring among adults with HIV receiving antiretroviral therapy in Uganda: randomised trial. BMJ. 2011;343:d6792.CrossRef
26.
go back to reference Ingle SM, et al. Impact of risk factors for specific causes of death in the first and subsequent years of antiretroviral therapy among HIV-infected patients. Clin Infect Dis. 2014;59(2):287–97.CrossRef Ingle SM, et al. Impact of risk factors for specific causes of death in the first and subsequent years of antiretroviral therapy among HIV-infected patients. Clin Infect Dis. 2014;59(2):287–97.CrossRef
27.
go back to reference Moore RD, et al. Rate of comorbidities not related to HIV infection or AIDS among HIV-infected patients, by CD4 cell count and HAART use status. Clin Infect Dis. 2008;47(8):1102–4.CrossRef Moore RD, et al. Rate of comorbidities not related to HIV infection or AIDS among HIV-infected patients, by CD4 cell count and HAART use status. Clin Infect Dis. 2008;47(8):1102–4.CrossRef
28.
go back to reference Ross AC, et al. Relationship between inflammatory markers, endothelial activation markers, and carotid intima-media thickness in HIV-infected patients receiving antiretroviral therapy. Clin Infect Dis. 2009;49(7):1119–27.CrossRef Ross AC, et al. Relationship between inflammatory markers, endothelial activation markers, and carotid intima-media thickness in HIV-infected patients receiving antiretroviral therapy. Clin Infect Dis. 2009;49(7):1119–27.CrossRef
29.
go back to reference Karat, A.S., et al., Measuring mortality due to HIV-associated tuberculosis among adults in South Africa: comparing verbal autopsy, minimally-invasive autopsy, and research data. PLoS One, 2017. 12(3): p. e0174097. Karat, A.S., et al., Measuring mortality due to HIV-associated tuberculosis among adults in South Africa: comparing verbal autopsy, minimally-invasive autopsy, and research data. PLoS One, 2017. 12(3): p. e0174097.
30.
go back to reference Cox JA, et al. Autopsy acceptance rate and reasons for decline in Mulago hospital, Kampala, Uganda. Tropical Med Int Health. 2011;16(8):1015–8.CrossRef Cox JA, et al. Autopsy acceptance rate and reasons for decline in Mulago hospital, Kampala, Uganda. Tropical Med Int Health. 2011;16(8):1015–8.CrossRef
31.
go back to reference Song A, et al. From CD4-based initiation to treating all HIV-infected adults immediately: an evidence-based meta-analysis. Front Immunol. 2018;9:212.CrossRef Song A, et al. From CD4-based initiation to treating all HIV-infected adults immediately: an evidence-based meta-analysis. Front Immunol. 2018;9:212.CrossRef
32.
go back to reference Katz IT, Maughan-Brown B. Improved life expectancy of people living with HIV: who is left behind? Lancet HIV. 2017;4(8):e324–6.CrossRef Katz IT, Maughan-Brown B. Improved life expectancy of people living with HIV: who is left behind? Lancet HIV. 2017;4(8):e324–6.CrossRef
Metadata
Title
A decade of antiretroviral therapy in Uganda: what are the emerging causes of death?
Authors
Agnes N. Kiragga
Frank Mubiru
Andrew D. Kambugu
Moses R. Kamya
Barbara Castelnuovo
Publication date
01-12-2019

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