@article{59e501406ac34c48935275f5c4f4301e,
title = "Temporal trends of early mortality and its risk factors in HIV-infected adults initiating antiretroviral therapy in Uganda",
abstract = "Background: A decline in mortality rates during the first 12 months of antiretroviral therapy (ART) has been mainly linked to increased ART initiation at higher CD4 counts and at less advanced World Health Organization (WHO) clinical stages of HIV infection; however, the role of improved patient care has not been well studied. We estimated improvements in early mortality due to improved patient care. Methods: We conducted a retrospective cohort study of HIV-infected individuals ages 18 and older who initiated ART at the Mengo HIV Counseling and Home Care Clinic between 2006 and 2016. We conducted a mediation analysis using generalized structural equation models with inverse odds ratio weighting to estimate the natural direct and indirect effects of ART initiation time on early mortality. Findings: Among 6,847 patients, most were female (69%), with a median age of 32 (interquartile range [IQR] = 28–38), versus a median age of 38 (IQR = 32–45) for males. The median CD4 count at ART initiation increased from 142 cells/ul (95% confidence interval [CI] = 135–150) in 2006–2010 to 302 cells/ul (95% CI = 283–323) in 2015–2016 (p < 0·001). The number of patients at WHO clinical stages I/II increased from 52% in 2006–2010 to 78% in 2015–2016 (p < 0·001). Annual early mortality decreased from 8·8 deaths/100 person years (PYS) in 2006 to 2.5 deaths/100 pys in 2016 (p < 0·001). Mediation by CD4 counts and WHO clinical stages accounted for 54% of the total effect of ART initiation timing on early mortality. In comparison, 46% remained as the direct effect, reflecting the contribution of improved patient care. Interpretation: Improved patient care practices should be promoted as a strategy for reducing early mortality after ART initiation, above and beyond the effects from ART initiation at higher CD4 counts and less advanced WHO clinical stage alone. Funding: This research was supported by the President's Emergency Plan for AIDS Relief (PEPFAR), the National Institute of Allergy and Infectious Diseases Division of Intramural Research, and the National Cancer Institute.",
author = "Victor Ssempijja and Edith Namulema and Racheal Ankunda and Quinn, {Thomas C.} and Frank Cobelens and Hoog, {Anja van't} and Reynolds, {Steven J.}",
note = "Funding Information: This project was supported by the Division of Intramural Research , National Institute of Allergy and Infectious Diseases , National Institutes of Health ( AI001040 ). It was also funded in whole or in part with federal funds from the National Cancer Institute , National Institutes of Health , under Contract No. HHSN261200800001E . The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. Support for treatment services was provided by the President's Emergency Plan for AIDS Relief through CDC Uganda. Funding Information: This project was supported by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health (AI001040). It was also funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. Support for treatment services was provided by the President's Emergency Plan for AIDS Relief through CDC Uganda. The authors thank the Mengo HIV Counseling and Home Care Clinic ART treatment program patients and staff whose contributions made this work possible. VS developed the research concept, performed data management, data analysis, data interpretation and writing. EN and RA supported concept development, provided oversight to data collection, helped with data management, data analysis, data interpretation and editing of writing. TCQ helped with data analysis, data interpretation, editing of writing and with securing of funding. FC and Dr AH supported concept development, data interpretation and editing of writing. SJR supported concept development, data analysis, data interpretation, editing of writing and with securing of funding. De-identified data that underlie the results reported in this article can be requested through the corresponding author for approved research concepts. Publisher Copyright: {\textcopyright} 2020 The Author(s) Copyright: Copyright 2020 Elsevier B.V., All rights reserved.",
year = "2020",
month = nov,
doi = "https://doi.org/10.1016/j.eclinm.2020.100600",
language = "English",
volume = "28",
journal = "EClinicalMedicine",
issn = "2589-5370",
publisher = "Lancet Publishing Group",
}