Background:  Cumulative exposure to PI has been shown to increase the risk of myocardial infarction (MI) and more recently specific NRTI, such as abacavir, have also been incriminated. Our objectives were to analyze the effect of exposure to specific NRTI and PI on the risk of MI in the French Hospital Database on HIV using a nested case-control study.

Methods:  Cases were patients enrolled in the database who, between January 2000 and December 2006, had a first MI prospectively reported, definite or probable after validation using the European Society of Cardiology definition. As many as 5 controls were selected at random with replacement among patients with no history of MI, followed at the time of MI diagnosis, matched with the case for age (±3 years), sex, and clinical center of follow-up. Data on cardiovascular risk factors and cardiovascular treatments were collected from the medical records. Conditional logistic regression models were used to assess the association of cumulative and/or recent (current or within last 6 months) and past (>6 months ago) use of each NRTI (AZT, DDI, DDC, D4T, 3TC, ABC, TNF, FTC) and cumulative use of each PI (IDV, SQV, NFV, LPV, APV/fPV), after adjustment for known cardiovascular risk factors, plasma HIV-1 RNA, CD4/CD8 ratio and use of other antiretrovirals.

Results:  Overall 286 cases and 865 controls were included in the analysis, 76% enrolled in the FHDH while ARV naive. Cases were mainly male (89%) with a median age of 47 years. For abacavir (ABC), there was evidence of an interaction between recent and cumulative exposure and, after exploration, we found an increased risk of MI in those with <1 year of exposure and recent use (OR=2.19, 95%CI: 1.19-4.02) but not in others. No interaction was found between exposure to abacavir and the number of cardiovascular risk factors. No other NRTI was associated with the risk of MI. Cumulative exposure to PI were associated with an increased risk of MI for all (indinavir [IDV] OR = 1.11 per year, 95%CI 0.98 to 1.25 and nelfinavir [NFV] OR = 1.13/year, 95%CI 0.99 to 1.30) except saquinavir (SQV) (OR = 0.96/year, 95%CI 0.80 to 1.15), reaching significance for lopinavir (LPV) (OR = 1.38/year, 95%CI 1.10 to 1.74), and amprenavir (APV)/fos-amprenavir (fPV) (OR = 1.55/year, 95%CI 1.20 to 1.99).

Conclusions:  In our study, we found that the risk of MI was increased by cumulative exposure to LPV and to APV or fPV. Initiating ABC was also associated with an increased risk of MI while longer exposure to ABC was not.