The effect of cumulating exposure to abacavir on the risk of cardiovascular disease events in patients from the Swiss HIV Cohort Study.

Young, Jim; Xiao, Yongling; Moodie, Erica E M; Abrahamowicz, Michal; Klein, Marina B; Bernasconi, Enos; Schmid, Patrick; Calmy, Alexandra; Cavassini, Matthias; Cusini, Alexia; Weber, Rainer; Bucher, Heiner C (2015). The effect of cumulating exposure to abacavir on the risk of cardiovascular disease events in patients from the Swiss HIV Cohort Study. Journal of acquired immune deficiency syndromes JAIDS, 69(4), pp. 413-421. Lippincott Williams & Wilkins 10.1097/QAI.0000000000000662

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BACKGROUND Patients with HIV exposed to the antiretroviral drug abacavir may have an increased risk of cardiovascular disease (CVD). There is concern that this association arises because of a channelling bias. Even if exposure is a risk, it is not clear how that risk changes as exposure cumulates. METHODS We assess the effect of exposure to abacavir on the risk of CVD events in the Swiss HIV Cohort Study. We use a new marginal structural Cox model to estimate the effect of abacavir as a flexible function of past exposures while accounting for risk factors that potentially lie on a causal pathway between exposure to abacavir and CVD. RESULTS 11,856 patients were followed for a median of 6.6 years; 365 patients had a CVD event (4.6 events per 1000 patient years). In a conventional Cox model, recent - but not cumulative - exposure to abacavir increased the risk of a CVD event. In the new marginal structural Cox model, continued exposure to abacavir during the past four years increased the risk of a CVD event (hazard ratio 2.06, 95% confidence interval 1.43-2.98). The estimated function for the effect of past exposures suggests that exposure during the past 6 to 36 months caused the greatest increase in risk. CONCLUSIONS Abacavir increases the risk of a CVD event: the effect of exposure is not immediate, rather the risk increases as exposure cumulates over the past few years. This gradual increase in risk is not consistent with a rapidly acting mechanism, such as acute inflammation.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Infectiology

UniBE Contributor:

Cusini, Alexia

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0894-9255

Publisher:

Lippincott Williams & Wilkins

Language:

English

Submitter:

Annelies Luginbühl

Date Deposited:

28 May 2015 08:30

Last Modified:

23 Jul 2015 08:39

Publisher DOI:

10.1097/QAI.0000000000000662

PubMed ID:

25932884

BORIS DOI:

10.7892/boris.68974

URI:

https://boris.unibe.ch/id/eprint/68974

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