HAART-associated hyperlipidaemia linked to low risk for cardiovascular disease (CVD)

Results from one of the more potentially optimistic studies first presented at the 4th International Lipodystrophy Workshop last autumn have been published in full in the 24 January 2003 issue of AIDS.

In summary the study found that hyperipidaemia in its HIV cohort was largely due to increased VLDL cholesterol and that this may mean HAART-associated hyperipidaemia may be less of a risk factor for CVD than previously feared.

Increased levels of cholesterol and triglycerides are a well-described side effect associated with HAART therapy and the overlap of symptoms with cardiovascular risk factors has been a cause of concern and focus for research. Although case reports of cardiovascular disease (CVD) in young HIV-positive men and women have been reported, analysis of CVD events from large cohort studies have not proved conclusive. One difficulty with these studies has been their relative short duration and that risk factors for CVD in the HIV-negative population accumulate over 20-30 years.

Dr Stefan Mauss and colleagues from the Centre for HIV and Hepatogastroenterology in Dusseldorf looked at the lipoprotein pattern from fasting serum samples from 187 consecutive antiretroviral-treated and untreated HIV-positive patients and compared these to 10 individuals with familial combined hyperlipidaemia (high cardiovascular risk) and 14 with familial hypertriglyceridaemia (low cardiovascular risk).

Total cholesterol, low density lipoprotein (LDL) cholesterol, high density lipoprotein (HDL) cholesterol, triglycerides, apolipoprotein A1 and B were determined in serum. Very low density lipoprotein (VLDL) was prepared by ultracentrifugation and analysed for cholesterol, triglycerides and apolipoprotein B.

Lipoprotein disorders were found in 114/187 HIV-positive patients (61%). Of these, 10% had elevated LDL-cholesterol, 14% elevated LDL- and VLDL-cholesterol and 76% had elevated VLDL-cholesterol. The ratio of VLDL-triglycerides to VLDL-apolipoprotein B in 34 HIV-positive patients with hyperlipidaemia patients was similar to the 14 patients with famlial hypertriglyceridaemia, but differed substantially from 10 patients with familial combined hyperlipidaemia (P < 0.0001).

The authors concluded “that the large subgroup of HIV-positive patients taking antiretroviral treatment and with hypercholesterolaemia caused by increased VLDL may have a lower cardiovascular risk than generally expected. A differentiated analysis of the lipoprotein pattern should be included in prospective studies assessing the cardiovascular risk of HIV-positive patients to test this hypothesis. However, the contribution of other important cardiovascular risk factors frequently found in HIV-positive patients taking antiretroviral treatment, such as insulin resistance, must also be considered in prospective studies.”

Mauss S, Stechel J, Willers R et al. Differentiating hyperlipidaemia associated with antiretroviral therapy. AIDS 2003; 17(2):189-194

Comment

Higher risks of cardiovascular disease associated with antiretroviral treatment was one of the most debated issues at the CROI conference.

The first results from the international D:A:D study indicated that this may be as high as 27% increased risk per year of antiretroval use and was supported by at least one longitudinal study looking at intima media thickness of the carotid artery. These, and other, at first sight, contradictory studies will be reported in the next HTB.

It was emphasised that for many people who are already at a low risk, this increased risk still remains very low and is generally outweighed by the benefits of HAART. For people already in a higher risk group, lifestyle changes including diet, smoking cessation and exercise are even more important. Clearly, a patients risk of cardiovascular disease should be taken into account when prescribing antiretroviral treatment.