Effect of Cumulating Exposure to Abacavir on the Risk of Cardiovascular Disease Events in Patients From the Swiss HIV Cohort Study.
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 channeling 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
A total of 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 4 years increased the risk of a CVD event (hazard ratio = 2.06; 95% confidence interval: 1.43 to 2.98). The estimated function for the effect of past exposures suggests that exposure during the past 6-36 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.
*Basel Institute for Clinical Epidemiology and Biostatistics, University Hospital Basel, Basel, Switzerland; †Analysis Group Inc, Montreal, QC, Canada; ‡Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, QC, Canada; §Department of Medicine, Royal Victoria Hospital, McGill University Health Centre, Montreal, QC, Canada; ‖Division of Infectious Diseases, Regional Hospital of Lugano, Lugano, Switzerland; ¶Division of Infectious Diseases and Hospital Epidemiology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland; #Division of Infectious Diseases, University Hospital Geneva, Geneva, Switzerland; **Division of Infectious Diseases, University Hospital Lausanne, Lausanne, Switzerland; ††Department of Infectious Diseases, Bern University Hospital and University of Bern, Bern, Switzerland; ‡‡Division of Infectious Diseases and Hospital Epidemiology, University Hospital and University of Zürich, Zürich, Switzerland; and §§Division of Infectious Diseases and Hospital Epidemiology, University Hospital Basel, Basel, Switzerland.
Jim
J
Young
Yongling
Y
Xiao
Erica E M
EE
Moodie
Michal
M
Abrahamowicz
Marina B
MB
Klein
Enos
E
Bernasconi
Patrick
P
Schmid
Alexandra
A
Calmy
Matthias
M
Cavassini
Alexia
A
Cusini
Rainer
R
Weber
Heiner C
HC
Bucher
D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000139:chemically induced*; D015224:Dideoxynucleosides / Q000009:adverse effects* / Q000627:therapeutic use*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000453:epidemiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D013557:Switzerland / Q000453:epidemiology; D000099227:Abacavir
D019380:Anti-HIV Agents; D015224:Dideoxynucleosides; D000099227:Abacavir