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

April C Pettit; Mark J Giganti; Suzanne M Ingle; Margaret T May; Bryan E Shepherd; Michael J Gill; Gerd Fätkenheuer; Sophie Abgrall; Michael S Saag; Julia Del Amo; Amy C Justice; Jose M Miro; Matthias Cavasinni; François Dabis; Antonella D Monforte; Peter Reiss; Jodie Guest; David Moore; Leah Shepherd; Niels Obel; Heidi M Crane; Colette Smith; Ramon Teira; Robert Zangerle; Jonathan Ac Sterne; Timothy R Sterling; Antiretroviral Therapy Cohort Collaboration (ART-CC) investigators

doi:10.1002/jia2.25031

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

April C Pettit, Mark J Giganti, Suzanne M Ingle, Margaret T May, Bryan E Shepherd, Michael J Gill, Gerd Fätkenheuer, Sophie Abgrall, Michael S Saag, Julia Del Amo, Amy C Justice, Jose M Miro, Matthias Cavasinni, François Dabis, Antonella D Monforte, Peter Reiss, Jodie Guest, David Moore, Leah Shepherd, Niels ObelHeidi M Crane, Colette Smith, Ramon Teira, Robert Zangerle, Jonathan Ac Sterne, Timothy R Sterling, Antiretroviral Therapy Cohort Collaboration (ART-CC) investigators

31 Citationer (Scopus)

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.

Originalsprog	Engelsk
Artikelnummer	e25031
Tidsskrift	Journal of the International AIDS Society
Vol/bind	21
Udgave nummer	1
ISSN	1758-2652
DOI	https://doi.org/10.1002/jia2.25031
Status	Udgivet - jan. 2018

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10.1002/jia2.25031

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Pettit, A. C., Giganti, M. J., Ingle, S. M., May, M. T., Shepherd, B. E., Gill, M. J., Fätkenheuer, G., Abgrall, S., Saag, M. S., Del Amo, J., Justice, A. C., Miro, J. M., Cavasinni, M., Dabis, F., Monforte, A. D., Reiss, P., Guest, J., Moore, D., Shepherd, L., ... Antiretroviral Therapy Cohort Collaboration (ART-CC) investigators (2018). Increased non-AIDS mortality among persons with AIDS-defining events after antiretroviral therapy initiation. Journal of the International AIDS Society, 21(1), [e25031]. https://doi.org/10.1002/jia2.25031

Pettit, AC, Giganti, MJ, Ingle, SM, May, MT, Shepherd, BE, Gill, MJ, Fätkenheuer, G, Abgrall, S, Saag, MS, Del Amo, J, Justice, AC, Miro, JM, Cavasinni, M, Dabis, F, Monforte, AD, Reiss, P, Guest, J, Moore, D, Shepherd, L, Obel, N, Crane, HM, Smith, C, Teira, R, Zangerle, R, Sterne, JA, Sterling, TR & Antiretroviral Therapy Cohort Collaboration (ART-CC) investigators 2018, 'Increased non-AIDS mortality among persons with AIDS-defining events after antiretroviral therapy initiation', Journal of the International AIDS Society, bind 21, nr. 1, e25031. https://doi.org/10.1002/jia2.25031

@article{af906e6ce53343599c820726888cee58,

title = "Increased non-AIDS mortality among persons with AIDS-defining events after antiretroviral therapy initiation",

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-na{\"i}ve 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 = "Journal Article",

author = "Pettit, {April C} and Giganti, {Mark J} and Ingle, {Suzanne M} and May, {Margaret T} and Shepherd, {Bryan E} and Gill, {Michael J} and Gerd F{\"a}tkenheuer and Sophie Abgrall and Saag, {Michael S} and {Del Amo}, Julia and Justice, {Amy C} and Miro, {Jose M} and Matthias Cavasinni and Fran{\c c}ois Dabis and Monforte, {Antonella D} 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 Sterne, {Jonathan Ac} and Sterling, {Timothy R} and {Antiretroviral Therapy Cohort Collaboration (ART-CC) investigators}",

note = "{\textcopyright} 2018 The Authors. Journal of the International AIDS Society published by John Wiley & sons Ltd on behalf of the International AIDS Society.",

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 Ltd",

number = "1",

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TY - JOUR

T1 - Increased non-AIDS mortality among persons with AIDS-defining events after antiretroviral therapy initiation

AU - Pettit, April C

AU - Giganti, Mark J

AU - Ingle, Suzanne M

AU - May, Margaret T

AU - Shepherd, Bryan E

AU - Gill, Michael J

AU - Fätkenheuer, Gerd

AU - Abgrall, Sophie

AU - Saag, Michael S

AU - Del Amo, Julia

AU - Justice, Amy C

AU - Miro, Jose M

AU - Cavasinni, Matthias

AU - Dabis, François

AU - Monforte, Antonella D

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 Ac

AU - Sterling, Timothy R

AU - Antiretroviral Therapy Cohort Collaboration (ART-CC) investigators

PY - 2018/1

Y1 - 2018/1

N2 - 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.

AB - 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.

KW - Journal Article

U2 - 10.1002/jia2.25031

DO - 10.1002/jia2.25031

M3 - Journal article

C2 - 29334197

VL - 21

JO - Journal of the International AIDS Society

JF - Journal of the International AIDS Society

SN - 1758-2652

IS - 1

M1 - e25031

ER -

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

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