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Conference
"Emerging data regarding the effect of antiretroviral therapy on lipid profiles" Dr. Peter Reiss (biography) English - 2002-04-26 - 30 minutes
(24 slides)
Summary : Access to combination antiretroviral therapy in industrialized countries has resulted in unprecedented reductions in HIV-associated morbidity and mortality. However, follow up of patients in clinical trials and observational cohorts has revealed a high rate of adverse events associated with current treatment regimens. A significant proportion of patients change their treatment regimen because of drug intolerance and/or toxicity within the first year of initiating treatment.
A common adverse effect, which occurs in at least 50% of patients, is the “lipodystrophy syndrome”. This syndrome is characterized by a disruption of normal fat and glucose metabolism resulting in hyperlipidaemia; glucose intolerance due to insulin resistance; and noticeable changes in body appearance as a result of an abnormal distribution of body fat. Subcutaneous fat is lost in the peripheral parts of the body (arms, legs, face, buttocks), while fat accumulation occurs in other parts (inside the abdominal cavity, dorsocervical, breasts). Although initially it was assumed that these changes were solely associated with use of protease inhibitors (PI), it is now clear that other classes of antiretroviral drugs, particularly the nucleoside analogue reverse transcriptase inhibitors (nNRTI), play a role. Host genetic factors and possibly HIV itself or the immune response against the virus may also contribute. Although certain components of the lipodystrophy syndrome are understood, the comprehensive pathogenesis of the syndrome remains unresolved. As a result, there is a paucity of therapeutic options to reverse the syndrome once it has developed. There is a growing concern that the syndrome, or at least certain of its components such as hyperlipidaemia, may be associated with an increased risk of developing premature atheriosclerosis and cardiovascular disease.
Currently available PI-containing regimens are associated with elevations in LDL-cholesterol and triglycerides, which are presumed to be deleterious to the patient. However, several studies have shown remarkable rises in HDL-cholesterol plasma levels in patients taking nevirapine-containing regimens, either as a 1st line regimen or to replace the PI component of a regimen. These increases in HDL-cholesterol plasma levels greatly surpass those observed with statins. Similar findings have been reported for efavirenz. The mechanism by which nNRTIs induce rises in HDL-cholesterol plasma levels remains to be elucidated. These lipid profiles, however, are in marked contrast to those associated with the use of PIs and would be expected to result in a reduced risk of (premature) atherosclerosis.
Learning objectives : The participant will be able to distinguish the effects of different kinds of antiretroviral therapy (ART) on the patient's lipid profile, e.g., the effects of NNRTIs versus PIs.
Conclusions of the FRAM and DAD studies.
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