However, clinicians disagree about the implications of relatively short term lipid elevations in people on HAART.
Dr Stefan Mauss, one of Germany’s leading HIV clinicians, recently looked at the make up of the cholesterol in the bloodstreams of 172 of his patients, and found that it may not be as atherogenic as first thought. He looked at the proportion of VLDL to LDL cholesterol particles, and found that the ratio of VLDL cholesterol to total cholesterol was much higher than in people with elevated cholesterol in the general population. When VLDL cholesterol is elevated in this way, the risk of heart disease is lowered. Less than one third of patients with a high total cholesterol had elevated LDL cholesterol.
“I used to treat very aggressively but now I would treat [cholesterol elevations] in patients with multiple risk factors and elevated LDL cholesterol” he told aidsmap.
Dr Jonathan Cartledge of London’s University College Medical School is also skeptical.
“I’m not convinced that just because we are seeing intima media thickening in people on HAART, that this translates into a long term increase in risk – if people stop or switch therapy, we know that the cholesterol goes down. Also, people may typically only be on protease inhibitors for a few years and other therapies in the future may not have the same effect [on lipids]. I'm not sure that short-term elevations will have the same effect on long-term risk as lifestyle factors which may go on for years and years, such as smoking.”
Dr Graeme Moyle of the Chelsea and Westminster Hospital pointed out that it may be far too early to tell whether treatment of lipid elevations will have an effect on clinical outcomes – and in the meantime, it may be expensive and may carry more risks than benefits.
“Are we really treating a blood test result, or are we doing something that’s going to beneficial in our patients, given the numbers needed to treat in order to show benefit?” he asked during a discussion on the effects of statin therapy on cardiovascular risk. A major study of pravastatin in Scotland found that 45 men with hypercholesterolemia must be treated for five years to prevent one non-fatal heart attack or death from cardiovascular causes, and 143 men must be treated to prevent one death from a cardiac cause (Shepherd).
In other studies, statins have only been shown to affect survival after at least eighteen months of treatment, suggesting that short term reductions in lipid levels have no effect on the risk of cardiovascular disease.
This means that long-term data from studies of switching therapy will be needed in order to show that any trends are sustained. At the Lipodystrophy Workshop Allain Lafeuillade presented 48 week results of the Trizal study, which looked at the effects of switching from stable PI-containing therapy to Trizivir.
This study showed that after 48 weeks, there was no difference in the percentage with viral load below 50 copies, but cholesterol and triglyceride levels fell significantly in the Trizivir group (median cholesterol reduction –0.80 mmol/L). However, cholesterol also fell by 0.44mmol/L in the continued HAART group (individuals with 24 months prior HAART and a median baseline cholesterol of 5.6mmol/L). This reduction was also statistically significant, despite the fact that cholesterol elevations worsened in 29% of the PI recipients.
A study from Houston, Texas, showed that in patients with high lipid levels, lipid lowering therapy was only partially successful. Sixty three consecutive patients were analysed. A mean cholesterol reduction of 19% was reported on the first lipid-lowering regimen (predominantly fibrates), and LDL cholesterol levels fell by just 5%. Only 16% of patients who continued protease inhibitor therapy achieved target levels of LDL and total cholesterol after more than one year of lipid-lowering treatment. Presenting the study, Dr Fahmida Visnegarwala said that management of dyslipidemia alone without correcting the underlying metabolic disturbances may not be effective, but Dr Michael Dube of the University of Indiana pointed out that a disappointingly small proportion of non-HIV patients (typically less than 40%) ever reach the lipid goals set out at the beginning of lipid-lowering therapy.
Another issue relevant to the use of lipid lowering drugs is the impact of diet on the success of lipid lowering drugs. Dr Carl Grunfeld noted that in patients with high triglyceride levels, adherence to a diet designed to lower triglyceride levels has improved the effects of lipid-lowering drugs. On its own, dietary adjustment in HIV-positive patients with lipid elevations did not result in significant cholesterol reductions in a study carried out by Dr Graeme Moyle at the Chelsea and Westminster Hospital, and when patients received pravastatin plus dietary advice in an open label study, adherence to dietary advice was poorer than in the dietary advice arm of the study.