Heart Disease Risk Remains in Absence of HIV Treatment
September 18, 2007
By Tim Horn
There is growing evidence to suggest that untreated HIV infection may be a bigger threat to heart health than the lipid-raising effects of antiretroviral therapy. New data, reported by AIDS Clinical Trials Group (ACTG) researchers at the 47th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) in Chicago, may explain this unexpected twist in what experts thought they knew about cardiovascular disease risk in HIV-positive people.
In the 5,472-patients SMART study, which compared treatment interruptions to ongoing therapy, the risk of cardiovascular disease was higher among HIV-positive people who went off treatment—a surprising finding in light of the known lipid-raising effects of various antiretrovirals. At the time these data were first presented, in February 2007 at the 14th Conference on Retroviruses and Opportunistic Infections (CROI) in Los Angeles, few potential explanations were offered.
Pablo Tebas, MD, and his ACTG colleagues may have discovered a plausible theory, with data from one of the clinical trial network’s own treatment interruption study. While levels of artery-clogging total and “bad” LDL cholesterol may drop after HIV drug treatment is discontinued, so do levels of “good” HDL cholesterol that helps protect against blood-vessel-clogging arteriosclerosis. The study also points out that, with high viral loads in the absence of treatment, there are elevated blood levels of harmful inflammatory markers that may further increase the risk of damage to the cardiovascular system.
The study enrolled 47 HIV-positive patients on stable antiretroviral therapy with viral loads below 200 copies and CD4 counts above 500 cells. The volunteers were randomized to continue their HIV treatment for 18 weeks, either with or without the addition of interleukin-2 (IL-2), an experimental immune system stimulant. After 18 weeks, antiretroviral therapy was discontinued in all patients until their CD4 cell counts fell below 350.
Various metabolic parameters—such as glucose, cholesterol and triglyceride levels—were measured frequently in the patients while they remained off treatment. Markers of immune activation, including the number of a subset of activated CD8 cells in the blood, were also charted.
After eight weeks of interrupted treatment, total cholesterol decreased by an average of 32 mg/dL, triglycerides decreased by 35 mg/dL and LDL cholesterol decreased by 14 mg/dL. However, HDL cholesterol also dropped, causing unhealthy ratios of total cholesterol to HDL to remain the same. In other words, the changes in lipid levels did not effectively reduce the risk of cardiovascular disease after treatment was halted.
There were also marked increases in the inflammatory markers during the treatment interruption, further negating the lipid-lowering effects of the treatment interruption.
Dr. Tebas and his colleagues explained that while the decrease in total and LDL cholesterol might be associated with a decreased cardiovascular risk, those benefits might be offset by the marked decrease in HDL cholesterol. And with the increase in cellular activation, they concluded, “the simultaneous combination of these two phenomena—modest decreases in lipids with no net cardiovascular benefit and significant pro-inflammatory changes—could partially explain the increase in cardiovascular events observed in the SMART trial and other studies after the discontinuation of antiretroviral therapy.”
Source:
Tebas P, Henry K, Matinning R, et al. Antiretroviral treatment interruption, immune activation and cardiovascular risk [Abstract H-378]. 47th Interscience Conference on Antimicrobial Agents and Chemotherapy, Chicago, 2007.
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