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J Int AIDS Soc. 2018 Jan;21(1). doi: 10.1002/jia2.25031.

Increased non-AIDS mortality among persons with AIDS-defining events after antiretroviral therapy initiation.

Author information

1
Division of Infectious Diseases, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
2
Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN, USA.
3
Bristol Medical School, University of Bristol, Bristol, UK.
4
Division of Infectious Diseases, University of Calgary, Calgary, Canada.
5
Department of Internal Medicine, University of Cologne, Cologne, Germany.
6
Sorbonne Universités, UPMC Univ Paris 06, UMR_S 1136, Institut Pierre Louis d'Epidémiologie et de Santé Publique, Paris, France.
7
INSERM, UMR_S 1136, Institut Pierre Louis d'Epidémiologie et de Santé Publique, Paris, France.
8
Division of Infectious Disease, Department of Medicine, University of Alabama, Birmingham, AL, USA.
9
National Epidemiology Center, Carlos III Health Institute, Madrid, Spain.
10
Yale University School of Medicine, New Haven, CT, USA.
11
VA Connecticut Healthcare System, West Haven, CT, USA.
12
Hospital Clínic- Institut d'Investigacions Biomèdiques Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain.
13
Service of Infectious Diseases, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
14
INSERM U.1218 Bordeaux Population Health, ISPED, Bordeaux University, Bordeaux, France.
15
Clinic of Infectious Diseases & Tropical Medicine, San Paolo Hospital, University of Milan, Milan, Italy.
16
Stichting HIV Monitoring, Division of Infectious Diseases, Department of Global Health, Academic Medical Center, University of Amsterdam, Amsterdam Institute for Global Health and Development, Amsterdam, The Netherlands.
17
HIV Atlanta VA Cohort Study (HAVACS), Atlanta Veterans Affairs Medical Center, Decatur, GA, USA.
18
Division of Epidemiology and Population Health, British Columbia Centre for Excellence in HIV/AIDS, Vancouver, Canada.
19
Faculty of Medicine, University of British Columbia, Vancouver, Canada.
20
Research Department of Infection and Population Health, University College London, London, UK.
21
Department of Infectious Diseases, Copenhagen University Hospital, Copenhagen, Denmark.
22
Center for AIDS Research, University of Washington, Seattle, WA, USA.
23
Research Department of Infection and Population Health, UCL, London, UK.
24
Unit of Infectious Diseases, Hospital Sierrallana, Torrelavega, Spain.
25
Innsbruck Medical University, Innsbruck, Austria.

Abstract

INTRODUCTION:

HIV-1 infection leads to chronic inflammation and to an increased risk of non-AIDS mortality. Our objective was to determine whether AIDS-defining events (ADEs) were associated with increased overall and cause-specific non-AIDS related mortality after antiretroviral therapy (ART) initiation.

METHODS:

We included HIV treatment-naïve adults from the Antiretroviral Therapy Cohort Collaboration (ART-CC) who initiated ART from 1996 to 2014. Causes of death were assigned using the Coding Causes of Death in HIV (CoDe) protocol. The adjusted hazard ratio (aHR) for overall and cause-specific non-AIDS mortality among those with an ADE (all ADEs, tuberculosis (TB), Pneumocystis jiroveci pneumonia (PJP), and non-Hodgkin's lymphoma (NHL)) compared to those without an ADE was estimated using a marginal structural model.

RESULTS:

The adjusted hazard of overall non-AIDS mortality was higher among those with any ADE compared to those without any ADE (aHR 2.21, 95% confidence interval (CI) 2.00 to 2.43). The adjusted hazard of each of the cause-specific non-AIDS related deaths were higher among those with any ADE compared to those without, except metabolic deaths (malignancy aHR 2.59 (95% CI 2.13 to 3.14), accident/suicide/overdose aHR 1.37 (95% CI 1.05 to 1.79), cardiovascular aHR 1.95 (95% CI 1.54 to 2.48), infection aHR (95% CI 1.68 to 2.81), hepatic aHR 2.09 (95% CI 1.61 to 2.72), respiratory aHR 4.28 (95% CI 2.67 to 6.88), renal aHR 5.81 (95% CI 2.69 to 12.56) and central nervous aHR 1.53 (95% CI 1.18 to 5.44)). The risk of overall and cause-specific non-AIDS mortality differed depending on the specific ADE of interest (TB, PJP, NHL).

CONCLUSIONS:

In this large multi-centre cohort collaboration with standardized assignment of causes of death, non-AIDS mortality was twice as high among patients with an ADE compared to without an ADE. However, non-AIDS related mortality after an ADE depended on the ADE of interest. Although there may be unmeasured confounders, these findings suggest that a common pathway may be independently driving both ADEs and NADE mortality. While prevention of ADEs may reduce subsequent death due to NADEs following ART initiation, modification of risk factors for NADE mortality remains important after ADE survival.

KEYWORDS:

AIDS-defining events; Pneumocystis jiroveci pneumonia; marginal structural model; non-AIDS mortality; non-Hodgkin's lymphoma; tuberculosis

PMID:
29334197
PMCID:
PMC5810321
DOI:
10.1002/jia2.25031
[Indexed for MEDLINE]
Free PMC Article

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