Cardiovascular side effects of the antiretroviral agents rilpivirine, efavirenz, etravirine and abacavir: possible underlying mechanisms

The introduction of highly active antiretroviral therapy (HAART) has dramatically improved the life expectancy of HIV infected individuals. With the increased lifespan, complications associated with HAART are becoming more evident. Together with HIV itself and a higher prevalence of traditional risk factors, the antiretroviral agents are linked to an increase in cardiovascular diseases in the HIV population. In the present in vitro study the direct cardiac effects of a nucleoside reverse transcriptase inhibitor (NRTI) abacavir in combination with palmitic acid or cobalt chloride mimicking a diet high in saturated fatty acids or hypoxia respectively, were studied. Exposure to abacavir has been associated with an increased risk of myocardial infarction in clinical studies, but the damaging molecular mechanism remains elusive. Furthermore the in vitro cardiovascular effects of three non-nucleoside reverse transcriptase inhibitors (NNRTIs) were investigated; first generation NNRTI efavirenz and the second generation NNRTIs rilpivirine and etravirine.