Increased Non-AIDS Mortality among Persons with AIDS Defining Events after Antiretroviral Therapy Initiation

April C Pettit; Mark Giganti; Suzanne Ingle; Margaret May; Bryan Shepherd; Michael  Gill; Gerd Fatkenheuer; Sophie Abgrall; Michael Saag; Julia Del Amo; Amy Justice; Jose Miro; Matthias Cavasinni; François Dabis; Antonella D'Arminio Monforte; Peter Reiss; Jodie Guest; David Moore; Leah Shepherd; Niels Obel; Heidi M Crane; Colette Smith; Ramon Teira; Robert Zangerle; Jonathan Sterne; Timothy R Sterling

doi:10.1002/jia2.25031

Increased Non-AIDS Mortality among Persons with AIDS Defining Events after Antiretroviral Therapy Initiation

April C Pettit, Mark Giganti, Suzanne Ingle, Margaret May, Bryan Shepherd, Michael Gill, Gerd Fatkenheuer, Sophie Abgrall, Michael Saag, Julia Del Amo, Amy Justice, Jose Miro, Matthias Cavasinni, François Dabis, Antonella D'Arminio Monforte, Peter Reiss, Jodie Guest, David Moore, Leah Shepherd, Niels ObelHeidi M Crane, Colette Smith, Ramon Teira, Robert Zangerle, Jonathan Sterne, Timothy R Sterling

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Abstract

BACKGROUND: 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 1996-2014. 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] 2.00-2.43). 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 2.13-3.14], accident/suicide/overdose aHR 1.37 [95% CI 1.05-1.79], cardiovascular aHR 1.95 [95% CI 1.54-2.48, infection aHR [95% CI 1.68-2.81], hepatic aHR 2.09 [95% CI 1.61-2.72], respiratory aHR 4.28 [95% CI 2.67-6.88], renal aHR 5.81 [95% CI 2.69-12.56], and central nervous aHR 1.53 [95% CI 1.18-5.44]). 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-center 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.

Original language	English
Article number	e25031
Number of pages	8
Journal	Journal of the International AIDS Society
Volume	21
Issue number	1
Early online date	15 Jan 2018
DOIs	https://doi.org/10.1002/jia2.25031
Publication status	Published - Jan 2018

Keywords

AIDS defining events
Non-AIDS mortality
Tuberculosis
Pneumocystis jiroveci pneumonia
non-Hodgkin’s lymphoma
marginal structural model

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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ART-CC: Prognosis of HIV-infected patients treated with ART
Sterne, J. A. C. (Principal Investigator), Ingle, S. M. (Researcher) & May, M. T. (Co-Principal Investigator)
1/02/12 → 1/02/15
Project: Research
MONITORING AND MODELLING PROGNOSIS IN THE ERA OF HAART
Sterne, J. A. C. (Principal Investigator)
1/02/08 → 1/02/11
Project: Research
THE IMPACT OF HIGHLY EFFECTIVE ANTIRETROVIRAL THERAPY: MONITORING AND MODELLING BENEFIT AND HARM
Sterne, J. A. C. (Principal Investigator)
1/02/02 → 1/02/08
Project: Research

Cite this

Pettit, A. C., Giganti, M., Ingle, S., May, M., Shepherd, B., Gill, M., Fatkenheuer, G., Abgrall, S., Saag, M., Del Amo, J., Justice, A., Miro, J., Cavasinni, M., Dabis, F., D'Arminio Monforte, A., Reiss, P., Guest, J., Moore, D., Shepherd, L., ... Sterling, T. R. (2018). Increased Non-AIDS Mortality among Persons with AIDS Defining Events after Antiretroviral Therapy Initiation. Journal of the International AIDS Society, 21(1), Article e25031. https://doi.org/10.1002/jia2.25031

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title = "Increased Non-AIDS Mortality among Persons with AIDS Defining Events after Antiretroviral Therapy Initiation",

abstract = "BACKGROUND: 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-na{\"i}ve adults from the Antiretroviral Therapy Cohort Collaboration (ART-CC) who initiated ART from 1996-2014. 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{\textquoteright}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] 2.00-2.43). 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 2.13-3.14], accident/suicide/overdose aHR 1.37 [95% CI 1.05-1.79], cardiovascular aHR 1.95 [95% CI 1.54-2.48, infection aHR [95% CI 1.68-2.81], hepatic aHR 2.09 [95% CI 1.61-2.72], respiratory aHR 4.28 [95% CI 2.67-6.88], renal aHR 5.81 [95% CI 2.69-12.56], and central nervous aHR 1.53 [95% CI 1.18-5.44]). 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-center 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, Non-AIDS mortality, Tuberculosis, Pneumocystis jiroveci pneumonia, non-Hodgkin{\textquoteright}s lymphoma, marginal structural model",

author = "Pettit, {April C} and Mark Giganti and Suzanne Ingle and Margaret May and Bryan Shepherd and Michael Gill and Gerd Fatkenheuer and Sophie Abgrall and Michael Saag and {Del Amo}, Julia and Amy Justice and Jose Miro and Matthias Cavasinni and Fran{\c c}ois Dabis and {D'Arminio Monforte}, Antonella and Peter Reiss and Jodie Guest and David Moore and Leah Shepherd and Niels Obel and Crane, {Heidi M} and Colette Smith and Ramon Teira and Robert Zangerle and Jonathan Sterne and Sterling, {Timothy R}",

year = "2018",

month = jan,

doi = "10.1002/jia2.25031",

language = "English",

volume = "21",

journal = "Journal of the International AIDS Society",

issn = "1758-2652",

publisher = "BioMed Central",

number = "1",

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Pettit, AC, Giganti, M, Ingle, S, May, M, Shepherd, B, Gill, M, Fatkenheuer, G, Abgrall, S, Saag, M, Del Amo, J, Justice, A, Miro, J, Cavasinni, M, Dabis, F, D'Arminio Monforte, A, Reiss, P, Guest, J, Moore, D, Shepherd, L, Obel, N, Crane, HM, Smith, C, Teira, R, Zangerle, R, Sterne, J & Sterling, TR 2018, 'Increased Non-AIDS Mortality among Persons with AIDS Defining Events after Antiretroviral Therapy Initiation', Journal of the International AIDS Society, vol. 21, no. 1, e25031. https://doi.org/10.1002/jia2.25031

TY - JOUR

T1 - Increased Non-AIDS Mortality among Persons with AIDS Defining Events after Antiretroviral Therapy Initiation

AU - Pettit, April C

AU - Giganti, Mark

AU - Ingle, Suzanne

AU - May, Margaret

AU - Shepherd, Bryan

AU - Gill, Michael

AU - Fatkenheuer, Gerd

AU - Abgrall, Sophie

AU - Saag, Michael

AU - Del Amo, Julia

AU - Justice, Amy

AU - Miro, Jose

AU - Cavasinni, Matthias

AU - Dabis, François

AU - D'Arminio Monforte, Antonella

AU - Reiss, Peter

AU - Guest, Jodie

AU - Moore, David

AU - Shepherd, Leah

AU - Obel, Niels

AU - Crane, Heidi M

AU - Smith, Colette

AU - Teira, Ramon

AU - Zangerle, Robert

AU - Sterne, Jonathan

AU - Sterling, Timothy R

PY - 2018/1

Y1 - 2018/1

N2 - BACKGROUND: 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 1996-2014. 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] 2.00-2.43). 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 2.13-3.14], accident/suicide/overdose aHR 1.37 [95% CI 1.05-1.79], cardiovascular aHR 1.95 [95% CI 1.54-2.48, infection aHR [95% CI 1.68-2.81], hepatic aHR 2.09 [95% CI 1.61-2.72], respiratory aHR 4.28 [95% CI 2.67-6.88], renal aHR 5.81 [95% CI 2.69-12.56], and central nervous aHR 1.53 [95% CI 1.18-5.44]). 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-center 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.

AB - BACKGROUND: 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 1996-2014. 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] 2.00-2.43). 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 2.13-3.14], accident/suicide/overdose aHR 1.37 [95% CI 1.05-1.79], cardiovascular aHR 1.95 [95% CI 1.54-2.48, infection aHR [95% CI 1.68-2.81], hepatic aHR 2.09 [95% CI 1.61-2.72], respiratory aHR 4.28 [95% CI 2.67-6.88], renal aHR 5.81 [95% CI 2.69-12.56], and central nervous aHR 1.53 [95% CI 1.18-5.44]). 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-center 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.

KW - AIDS defining events

KW - Non-AIDS mortality

KW - Tuberculosis

KW - Pneumocystis jiroveci pneumonia

KW - non-Hodgkin’s lymphoma

KW - marginal structural model

U2 - 10.1002/jia2.25031

DO - 10.1002/jia2.25031

M3 - Article (Academic Journal)

C2 - 29334197

SN - 1758-2652

VL - 21

JO - Journal of the International AIDS Society

JF - Journal of the International AIDS Society

IS - 1

M1 - e25031

ER -

Increased Non-AIDS Mortality among Persons with AIDS Defining Events after Antiretroviral Therapy Initiation

Abstract

Keywords

UN SDGs

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Projects

ART-CC: Prognosis of HIV-infected patients treated with ART

MONITORING AND MODELLING PROGNOSIS IN THE ERA OF HAART

THE IMPACT OF HIGHLY EFFECTIVE ANTIRETROVIRAL THERAPY: MONITORING AND MODELLING BENEFIT AND HARM

Cite this