Atazanavir Advisory Committee Hearing Back-up Slides
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Fifth level
13 May 2003
The challenge is to identify individuals at increased vascular risk before they have a heart attack, stroke, or sudden cardiac death. The standard approach to risk assessment begins with determining levels of cardiac risk factors. The more severe the abnormality of the risk factor, the higher is the risk of a CHD event. Similarly, more risk factors have a synergistic effect at increasing risk. In some patients, noninvasive testing also may be useful
The challenge is to identify individuals at increased vascular risk before they have a heart attack, stroke, or sudden cardiac death. The standard approach to risk assessment begins with determining levels of cardiac risk factors. The more severe the abnormality of the risk factor, the higher is the risk of a CHD event. Similarly, more risk factors have a synergistic effect at increasing risk. In some patients, noninvasive testing also may be useful
Each year, 1.1 million Americans have a myocardial infarction (MI), 1/3 of which are fatal. For 1/3 of people, the first CHD event is a nonfatal MI. However, the incidence of death is high in the first year after an acute CHD event. Furthermore, survivors experience significant physical and emotional morbidity from CHF, arrhythmias, and an increased risk of sudden cardiac death
Cartoon to help explain the observed I50L phenotype result
First thing virus must do in presence of inhibitor is survive by quickly selecting a change that will decrease the inhibitory pressure exerted by the inhibitor, even if the virus become significantly impaired Once it has survived, it will select for additional changes that help it regain its viability or enzyme efficiency This is easily understandable with the emergence of the I50L change in the presence of ATV When ATV & SQV are used in combination, emergence of the I50L change would decrease susceptibility to ATV and increase susceptibility to SQV, resulting in viral inhibition and an unacceptable solution Selection of the I84V and other changes allows the virus to survive the inhibitory pressure of both ATV and SQV and live to fight another day