Purpose of reviewIn this review we will discuss the recent finding that different drug classes/antiretroviral therapy regimens may differ importantly with respect to their effect on the plasma lipid profile. On the basis of this we will illustrate how such differences, together with knowledge of the presence of other classic coronary artery disease risk factors, open the door for individualized treatment based on criteria in addition to the HIV-1 viral load and CD4 cell count.Recent findingsA large proportion of patients using protease inhibitor-based therapy develop insulin resistance and elevated plasma concentrations of LDL-cholesterol, total cholesterol and triglycerides, which has raised the concern that HIV-infected patients treated with antiretroviral therapy may be at an increased risk of developing premature coronary artery disease. Recent findings suggest that the use of non-nucleoside reverse transcriptase inhibitor-based therapy, in particular nevirapine, results in an elevation in HDL-cholesterol, which may be associated with a decreased incidence of coronary artery disease.SummaryIt is becoming increasingly important to carry out an adequate coronary artery disease risk assessment in each patient both before and approximately annually after the initiation of antiretroviral therapy. In patients with an already considerable risk of coronary artery disease based on traditional risk factors, particularly when it is expected to be difficult to modify these, starting with either a triple nucleoside reverse transcriptase inhibitor or a non-nucleoside reverse transcriptase inhibitor-based regimen may be the preferred option, given the propensity of such regimens to have either no effect or potentially even beneficial effects on the lipoprotein profile.