The risk of developing altered blood fat levels in patients taking protease inhibitor-based HIV treatment differs according to race, investigators from the United States report in the March edition of the freely available journal PLoS Medicine.
The study also showed that the influence of the gene apoC-III on blood fat levels varies according to a patient’s ethnic background.
Protease inhibitors are associated with elevations in the levels of triglycerides and certain types of cholesterol in the blood. These altered lipid levels can increase the risk of cardiovascular diseases such as heart attack and stroke.
In order to assess the influence of a patient’s racial background on the risk of cardiovascular disease, investigators measured the lipid content of blood samples taken from 626 patients who took part in various AIDS Clinical Trial Group (ACTG) studies. These included white, black and Hispanic patients, all of whom were taking antiretroviral drug combinations and had agreed to have their blood samples tested in future studies.
Eighty-nine per cent of the participants were men, the median age being 41 years and median CD4 cell count being 442 cells/mm3. Ninety-one per cent of the patients had viral loads below 400 copies/ml.
Using multivariate analysis, the investigators found that race had a significant influence on blood fat levels, when all other factors were taken into account (p < 0.001).
When they broke down their analysis by race, they found that black patients had lower triglyceride levels than white or Hispanic patients, suggesting that they are less likely to develop cardiovascular disease. The investigators also found that the black patients had higher levels of high-density lipoprotein (HDL or ‘good’) cholesterol and lower levels of non-HDL (or ‘bad’) cholesterol.
Overall, patients who were taking protease inhibitors also showed increases in triglyceride and non-HDL cholesterol levels, particularly when ‘boosted’ with low-dose ritonavir (Norvir). Compared with patients taking a non-nucleoside reverse transcriptase inhibitor (NNRTI)-based drug combination, those taking a boosted protease inhibitor had 46% increase in triglyceride levels (p < 0.05) and a 25% increase in non-HDL cholesterol (p < 0.001).
Black patients showed greater increases in blood fat levels when they were exposed to unboosted protease inhibitors, with a 39% increase in triglyceride levels compared with black patients taking NNRTIs. The effect of unboosted protease inhibitor treatment was not statistically significant in white or Hispanic patients, although all three groups showed raised triglyceride levels when exposed to ritonavir.
The investigators also examined the effect of variations in the gene apoC-III, which has been linked to blood fat levels in previous studies of white patients. Although the exact functions of the gene’s product are not known, this study showed that certain forms of the gene were linked to smaller increases in triglycerides in the Hispanic patients. This protects them from the drugs’ side-effects.
In contrast, the gene did not affect triglyceride levels in white or black patients.
“This study provides novel information regarding HIV-1 subgroups that may be at differential risk of developing metabolic and cardiovascular complications of antiretroviral therapy,” the investigators conclude.
“We found race / ethnic-specific differences in the plasma lipid levels on antiretroviral therapy, as well as differences in the influence of the apoC-III gene on the development of protease inhibitor-related hypertriglyceridaemia,” they write.
They point out, however, that further studies on the effects of racial differences and variations in the apoC-III gene are needed to confirm these findings. These should be prospective, allowing measurement of changes in blood fat levels over time and should include a careful assessment of other environmental and genetic factors, such as diet, smoking and other genes.
Despite its limitations, the study’s results may eventually help guide decisions about which patients should receive which drugs. They also emphasise the need for consideration of racial differences in the design of future studies on the complications of HIV therapy, particularly when they aim to examine the influence of genetic variation.
Foulkes AS et al. Associations among race/ethnicity, apoC-III genotypes, and lipids in HIV-1-infected individuals on antiretroviral therapy. PLoS Med 3: e52, 2006.