Effects of combination antiretroviral therapies on the risk of myocardial infarction among HIV patients.
BACKGROUND
Cohort studies have demonstrated greater risk of myocardial infarction (MI) associated with specific antiretroviral use, while meta-analyses of randomized controlled trials (RCTs) have not. These differences may be due to inherent biases in the observational study design or to the limited duration of randomized trials. We conducted a new-user, active-comparator cohort study emulating an RCT comparing the initiation of several antiretrovirals as part of combination antiretroviral therapy (cART) and MI.


METHODS
We included North Carolina (NC) Medicaid beneficiaries infected with human immunodeficiency virus between 2002 and 2008 who were previously untreated with cART. We compared hazard ratios (HRs) and 95% confidence intervals (CIs) of MI between abacavir and tenofovir recipients, and lopinavir-ritonavir or atazanavir recipients and nonnucleoside reverse transcriptase inhibitor (NNRTI) recipients. We adjusted for confounding through inverse probability weighting methods.


RESULTS
There were 3481 NC Medicaid new cART recipients who contributed 6399 person-years and experienced 38 MI events. Receiving abacavir compared with tenofovir as part of cART was associated with an increased rate of MI (unadjusted HR = 2.70 [95% CI = 1.24-5.91]; adjusted HR = 2.05 [0.72-5.86]). Point estimates also suggest a relationship between receipt of atazanavir or lopinavir-ritonavir compared with an NNRTI and MI, although estimates were imprecise.


CONCLUSIONS
We found an increased rate of MI among patients initiating abacavir compared with tenofovir, although the association was decreased after confounding adjustment. Without a very large prospective comparative clinical trial, a much larger observational study of patients initiating cART would be needed to better define this apparent association.
From the aDepartment of Pharmacy Practice and Science, Institute for Pharmaceutical Outcomes and Policy, University of Kentucky, Lexington, KY; bDepartment of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC; cDepartment of Medicine, Division of Infectious Diseases, University of North Carolina at Chapel Hill, Chapel Hill, NC; and dDepartment of Medicine, Division of Cardiology, University of North Carolina at Chapel Hill, Chapel Hill, NC.
Emily S
ES
Brouwer
Sonia
S
Napravnik
Joseph J
JJ
Eron
Brant
B
Stalzer
Michelle
M
Floris-Moore
Ross J
RJ
Simpson
Til
T
Stürmer
D000328:Adult; D017677:Age Distribution; D019380:Anti-HIV Agents / Q000009:adverse effects / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects*; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology*; D006801:Humans; D015994:Incidence; D053208:Kaplan-Meier Estimate; D008297:Male; D008484:Medicaid; D008875:Middle Aged; D009203:Myocardial Infarction / Q000139:chemically induced* / Q000453:epidemiology* / Q000503:physiopathology; D009657:North Carolina / Q000453:epidemiology; D011379:Prognosis; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D018570:Risk Assessment; D012720:Severity of Illness Index; D017678:Sex Distribution; D015996:Survival Rate; D014481:United States; D055815:Young Adult
D019380:Anti-HIV Agents