Is there continued evidence for an association between abacavir usage and myocardial infarction risk in individuals with HIV?: A cohort collaboration

Caroline A Sabin; Peter Reiss; Lene Ryom; Andrew N Phillips; Rainer Weber; Matthew Law; Eric Fontas; Amanda Mocroft; Stephane de Wit; Colette Smith; Francois Dabis; Antonella d'Arminio Monforte; Wafaa El-Sadr; Jens D Lundgren; D:A:D Study Group

doi:10.1186/s12916-016-0588-4

Is there continued evidence for an association between abacavir usage and myocardial infarction risk in individuals with HIV? A cohort collaboration

Caroline A Sabin, Peter Reiss, Lene Ryom, Andrew N Phillips, Rainer Weber, Matthew Law, Eric Fontas, Amanda Mocroft, Stephane de Wit, Colette Smith, Francois Dabis, Antonella d'Arminio Monforte, Wafaa El-Sadr, Jens D Lundgren, D:A:D Study Group

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Abstract

BACKGROUND: In March 2008, the D:A:D study published results demonstrating an increased risk of myocardial infarction (MI) for patients on abacavir (ABC). We describe changes to the use of ABC since this date, and investigate changes to the association between ABC and MI with subsequent follow-up.

METHODS: A total of 49,717 D:A:D participants were followed from study entry until the first of an MI, death, 1 February 2013 or 6 months after last visit. Associations between a person's 10-year cardiovascular disease (CVD) risk and the likelihood of initiating or discontinuing ABC were assessed using multivariable logistic/Poisson regression. Poisson regression was used to assess the association between current ABC use and MI risk, adjusting for potential confounders, and a test of interaction was performed to assess whether the association had changed in the post-March 2008 period.

RESULTS: Use of ABC increased from 10 % of the cohort in 2000 to 20 % in 2008, before stabilising at 18-19 %. Increases in use pre-March 2008, and subsequent decreases, were greatest in those at moderate and high CVD risk. Post-March 2008, those on ABC at moderate/high CVD risk were more likely to discontinue ABC than those at low/unknown CVD risk, regardless of viral load (≤1,000 copies/ml: relative rate 1.49 [95 % confidence interval 1.34-1.65]; >1,000 copies/ml: 1.23 [1.02-1.48]); no such associations were seen pre-March 2008. There was some evidence that antiretroviral therapy (ART)-naïve persons at moderate/high CVD risk post-March 2008 were less likely to initiate ABC than those at low/unknown CVD risk (odds ratio 0.74 [0.48-1.13]). By 1 February 2013, 941 MI events had occurred in 367,559 person-years. Current ABC use was associated with a 98 % increase in MI rate (RR 1.98 [1.72-2.29]) with no difference in the pre- (1.97 [1.68-2.33]) or post- (1.97 [1.43-2.72]) March 2008 periods (interaction P = 0.74).

CONCLUSIONS: Despite a reduction in the channelling of ABC for patients at higher CVD risk since 2008, we continue to observe an association between ABC use and MI risk. Whilst confounding cannot be fully ruled out, this further diminishes channelling bias as an explanation for our findings.

Original language	English
Article number	61
Journal	BMC Medicine
Volume	14
Number of pages	14
ISSN	1741-7015
DOIs	https://doi.org/10.1186/s12916-016-0588-4
Publication status	Published - 31 Mar 2016

Keywords

Adult
Anti-HIV Agents
Australia
Dideoxynucleosides
Europe
Female
HIV Infections
Humans
Logistic Models
Male
Medication Therapy Management
Middle Aged
Myocardial Infarction
Odds Ratio
Pharmacovigilance
Practice Patterns, Physicians'
Risk Assessment
Risk Factors
United States
Observational Study

UN SDGs

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

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Is there continued evidence for an association between abacavir usage and myocardial infarction risk in individuals with HIV? A cohort collaborationFinal published version, 652 KBLicence: CC BY

Cite this

Sabin, C. A., Reiss, P., Ryom, L., Phillips, A. N., Weber, R., Law, M., Fontas, E., Mocroft, A., de Wit, S., Smith, C., Dabis, F., d'Arminio Monforte, A., El-Sadr, W., Lundgren, J. D., & D:A:D Study Group (2016). Is there continued evidence for an association between abacavir usage and myocardial infarction risk in individuals with HIV? A cohort collaboration. BMC Medicine, 14, [61]. https://doi.org/10.1186/s12916-016-0588-4

Sabin, CA, Reiss, P, Ryom, L, Phillips, AN, Weber, R, Law, M, Fontas, E, Mocroft, A, de Wit, S, Smith, C, Dabis, F, d'Arminio Monforte, A, El-Sadr, W, Lundgren, JD & D:A:D Study Group 2016, 'Is there continued evidence for an association between abacavir usage and myocardial infarction risk in individuals with HIV? A cohort collaboration', BMC Medicine, vol. 14, 61. https://doi.org/10.1186/s12916-016-0588-4

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title = "Is there continued evidence for an association between abacavir usage and myocardial infarction risk in individuals with HIV?: A cohort collaboration",

abstract = "BACKGROUND: In March 2008, the D:A:D study published results demonstrating an increased risk of myocardial infarction (MI) for patients on abacavir (ABC). We describe changes to the use of ABC since this date, and investigate changes to the association between ABC and MI with subsequent follow-up.METHODS: A total of 49,717 D:A:D participants were followed from study entry until the first of an MI, death, 1 February 2013 or 6 months after last visit. Associations between a person's 10-year cardiovascular disease (CVD) risk and the likelihood of initiating or discontinuing ABC were assessed using multivariable logistic/Poisson regression. Poisson regression was used to assess the association between current ABC use and MI risk, adjusting for potential confounders, and a test of interaction was performed to assess whether the association had changed in the post-March 2008 period.RESULTS: Use of ABC increased from 10 % of the cohort in 2000 to 20 % in 2008, before stabilising at 18-19 %. Increases in use pre-March 2008, and subsequent decreases, were greatest in those at moderate and high CVD risk. Post-March 2008, those on ABC at moderate/high CVD risk were more likely to discontinue ABC than those at low/unknown CVD risk, regardless of viral load (≤1,000 copies/ml: relative rate 1.49 [95 % confidence interval 1.34-1.65]; >1,000 copies/ml: 1.23 [1.02-1.48]); no such associations were seen pre-March 2008. There was some evidence that antiretroviral therapy (ART)-na{\"i}ve persons at moderate/high CVD risk post-March 2008 were less likely to initiate ABC than those at low/unknown CVD risk (odds ratio 0.74 [0.48-1.13]). By 1 February 2013, 941 MI events had occurred in 367,559 person-years. Current ABC use was associated with a 98 % increase in MI rate (RR 1.98 [1.72-2.29]) with no difference in the pre- (1.97 [1.68-2.33]) or post- (1.97 [1.43-2.72]) March 2008 periods (interaction P = 0.74).CONCLUSIONS: Despite a reduction in the channelling of ABC for patients at higher CVD risk since 2008, we continue to observe an association between ABC use and MI risk. Whilst confounding cannot be fully ruled out, this further diminishes channelling bias as an explanation for our findings.",

keywords = "Adult, Anti-HIV Agents, Australia, Dideoxynucleosides, Europe, Female, HIV Infections, Humans, Logistic Models, Male, Medication Therapy Management, Middle Aged, Myocardial Infarction, Odds Ratio, Pharmacovigilance, Practice Patterns, Physicians', Risk Assessment, Risk Factors, United States, Observational Study",

author = "Sabin, {Caroline A} and Peter Reiss and Lene Ryom and Phillips, {Andrew N} and Rainer Weber and Matthew Law and Eric Fontas and Amanda Mocroft and {de Wit}, Stephane and Colette Smith and Francois Dabis and {d'Arminio Monforte}, Antonella and Wafaa El-Sadr and Lundgren, {Jens D} and {D:A:D Study Group}",

year = "2016",

month = mar,

day = "31",

doi = "10.1186/s12916-016-0588-4",

language = "English",

volume = "14",

journal = "BMC Medicine",

issn = "1741-7015",

publisher = "BioMed Central Ltd.",

}

TY - JOUR

T1 - Is there continued evidence for an association between abacavir usage and myocardial infarction risk in individuals with HIV?

T2 - A cohort collaboration

AU - Sabin, Caroline A

AU - Reiss, Peter

AU - Ryom, Lene

AU - Phillips, Andrew N

AU - Weber, Rainer

AU - Law, Matthew

AU - Fontas, Eric

AU - Mocroft, Amanda

AU - de Wit, Stephane

AU - Smith, Colette

AU - Dabis, Francois

AU - d'Arminio Monforte, Antonella

AU - El-Sadr, Wafaa

AU - Lundgren, Jens D

AU - D:A:D Study Group

PY - 2016/3/31

Y1 - 2016/3/31

N2 - BACKGROUND: In March 2008, the D:A:D study published results demonstrating an increased risk of myocardial infarction (MI) for patients on abacavir (ABC). We describe changes to the use of ABC since this date, and investigate changes to the association between ABC and MI with subsequent follow-up.METHODS: A total of 49,717 D:A:D participants were followed from study entry until the first of an MI, death, 1 February 2013 or 6 months after last visit. Associations between a person's 10-year cardiovascular disease (CVD) risk and the likelihood of initiating or discontinuing ABC were assessed using multivariable logistic/Poisson regression. Poisson regression was used to assess the association between current ABC use and MI risk, adjusting for potential confounders, and a test of interaction was performed to assess whether the association had changed in the post-March 2008 period.RESULTS: Use of ABC increased from 10 % of the cohort in 2000 to 20 % in 2008, before stabilising at 18-19 %. Increases in use pre-March 2008, and subsequent decreases, were greatest in those at moderate and high CVD risk. Post-March 2008, those on ABC at moderate/high CVD risk were more likely to discontinue ABC than those at low/unknown CVD risk, regardless of viral load (≤1,000 copies/ml: relative rate 1.49 [95 % confidence interval 1.34-1.65]; >1,000 copies/ml: 1.23 [1.02-1.48]); no such associations were seen pre-March 2008. There was some evidence that antiretroviral therapy (ART)-naïve persons at moderate/high CVD risk post-March 2008 were less likely to initiate ABC than those at low/unknown CVD risk (odds ratio 0.74 [0.48-1.13]). By 1 February 2013, 941 MI events had occurred in 367,559 person-years. Current ABC use was associated with a 98 % increase in MI rate (RR 1.98 [1.72-2.29]) with no difference in the pre- (1.97 [1.68-2.33]) or post- (1.97 [1.43-2.72]) March 2008 periods (interaction P = 0.74).CONCLUSIONS: Despite a reduction in the channelling of ABC for patients at higher CVD risk since 2008, we continue to observe an association between ABC use and MI risk. Whilst confounding cannot be fully ruled out, this further diminishes channelling bias as an explanation for our findings.

AB - BACKGROUND: In March 2008, the D:A:D study published results demonstrating an increased risk of myocardial infarction (MI) for patients on abacavir (ABC). We describe changes to the use of ABC since this date, and investigate changes to the association between ABC and MI with subsequent follow-up.METHODS: A total of 49,717 D:A:D participants were followed from study entry until the first of an MI, death, 1 February 2013 or 6 months after last visit. Associations between a person's 10-year cardiovascular disease (CVD) risk and the likelihood of initiating or discontinuing ABC were assessed using multivariable logistic/Poisson regression. Poisson regression was used to assess the association between current ABC use and MI risk, adjusting for potential confounders, and a test of interaction was performed to assess whether the association had changed in the post-March 2008 period.RESULTS: Use of ABC increased from 10 % of the cohort in 2000 to 20 % in 2008, before stabilising at 18-19 %. Increases in use pre-March 2008, and subsequent decreases, were greatest in those at moderate and high CVD risk. Post-March 2008, those on ABC at moderate/high CVD risk were more likely to discontinue ABC than those at low/unknown CVD risk, regardless of viral load (≤1,000 copies/ml: relative rate 1.49 [95 % confidence interval 1.34-1.65]; >1,000 copies/ml: 1.23 [1.02-1.48]); no such associations were seen pre-March 2008. There was some evidence that antiretroviral therapy (ART)-naïve persons at moderate/high CVD risk post-March 2008 were less likely to initiate ABC than those at low/unknown CVD risk (odds ratio 0.74 [0.48-1.13]). By 1 February 2013, 941 MI events had occurred in 367,559 person-years. Current ABC use was associated with a 98 % increase in MI rate (RR 1.98 [1.72-2.29]) with no difference in the pre- (1.97 [1.68-2.33]) or post- (1.97 [1.43-2.72]) March 2008 periods (interaction P = 0.74).CONCLUSIONS: Despite a reduction in the channelling of ABC for patients at higher CVD risk since 2008, we continue to observe an association between ABC use and MI risk. Whilst confounding cannot be fully ruled out, this further diminishes channelling bias as an explanation for our findings.

KW - Adult

KW - Anti-HIV Agents

KW - Australia

KW - Dideoxynucleosides

KW - Europe

KW - Female

KW - HIV Infections

KW - Humans

KW - Logistic Models

KW - Male

KW - Medication Therapy Management

KW - Middle Aged

KW - Myocardial Infarction

KW - Odds Ratio

KW - Pharmacovigilance

KW - Practice Patterns, Physicians'

KW - Risk Assessment

KW - Risk Factors

KW - United States

KW - Observational Study

U2 - 10.1186/s12916-016-0588-4

DO - 10.1186/s12916-016-0588-4

M3 - Journal article

C2 - 27036962

SN - 1741-7015

VL - 14

JO - BMC Medicine

JF - BMC Medicine

M1 - 61

ER -