People with HIV had poorer responses to lipid-lowering drugs than the HIV-negative population, but these responses varied according to antiretroviral regimen and lipid-lowering drug, according to a major review of patients receiving treatment through California’s Kaiser Permanente managed care system in the San Francisco area. The findings were published in Annals of Internal Medicine.
The study is the largest and most rigorous comparison to date of the effects of lipid-lowering treatments in people with HIV and the general population.
Cholesterol and triglyceride levels may be altered in untreated people with HIV due to effects of HIV infection (lowered levels of 'good' HDL cholesterol and elevated triglyceride levels) or effects of some antiretroviral drugs, particularly all the protease inhibitors apart from atazanavir (elevated levels of 'bad' LDL cholesterol and triglycerides, normalisation of HDL cholesterol).
People with HIV may also have other risks for cardiovascular disease, including older age and a high rate of smoking.
In order to manage the risk of cardiovascular disease doctors usually recommend lifestyle changes such as a heart-friendly diet and regular exercise.
If these measures don’t bring down cholesterol and triglyceride levels, drug treatments may be used – normally pravastatin or atorvastatin to treat elevated LDL cholesterol, gemfibrozil or fenofibrate to bring down elevated triglycerides.
However, it is unclear if HIV patients can expect the same response to lipid-lowering therapy as their HIV-negative counterparts. Researchers with the Kaiser Permanente healthcare delivery system in California, which provides health care to around a quarter of the state’s citizens, decided to investigate using their comprehensive database on patients receiving care through the organisation’s clinics.
The study compared all HIV-positive patients diagnosed with dyslipidaemia who initiated lipid-lowering treatment between 1996 and 2005 with a control group of HIV-negative patients who also commenced treatment for elevated cholesterol or triglycerides during this period. HIV-negative patients were matched in the ratio 10:1 to HIV-positive patients by age, sex and year of first laboratory evidence of dyslipidaemia.
Dyslipidaemia was defined as:
- Elevated LDL cholesterol >4.1mmol/L, or >3.4mmol/L in combination with two or more additional risk factors for cardiovascular disease (e.g. smoking, diabetes).
- Elevated triglycerides > 5.7mmol/L
The researchers identified 616 HIV-positive patients and 5451 HIV-negative patients with raised LDL cholesterol levels, and 213 HIV-positive and 1490 HIV-negative patients with raised triglyceride levels.
At baseline HIV-positive patients had higher lipid levels and a higher prevalence of coronary disease risk factors, but less diabetes or previously diagnosed coronary disease. On average patients had seven months of lipid-lowering treatment, and at least two post-treatment lipid tests available for comparison.
The key outcomes measured were percentage and absolute changes in LDL cholesterol and triglycerides in response to any lipid-lowering treatment, to statins, to fibrates or to gemfibrozil.
Adjusted linear regression analysis showed that although LDL cholesterol responses to lipid-lowering therapy overall did not differ between the two groups, LDL cholesterol responses to statins were slightly poorer (25.6% reduction vs 28.3% in the HIV-negative group, p = 0.001). However when pravastatin was excluded, there was no significant difference in LDL cholesterol responses to statin treatment between the two groups.
Pravastatin is more frequently prescribed in people taking antiretroviral therapy because it does not interact with any antiretroviral apart from efavirenz, making it safer to use. Atorvastatin is also used frequently due to a lack of interactions.
Reductions in triglyceride levels as a result of gemfibrozil treatment were significantly smaller in HIV-positive people (44.2% vs 59.3%, p
People with HIV were more likely to experience one serious side-effect of statin treatment – rhabdomyolysis – as a result of lipid-lowering therapy (three hospitalisations versus one, p = 0.036), and a sixfold higher rate of laboratory abnormalities (liver enzymes and creatinine kinase) was noted. Discontinuation rates were similar to those reported in previous studies of lipid-lowering treatments in HIV-negative people.
"The good news is lipid-lowering therapy in HIV patients works - not quite as well as it does in patients without HIV, but close," explained Michael Silverberg of Kaiser Permanente. Given the challenges for treating high cholesterol in HIV patients and the more aggressive target lipid goals for all patients, optimising lifestyle factors such as obesity and hypertension are also important factors to monitor for those with HIV infection, he added.
Silverberg MJ et al. Comparison of response to newly prescribed lipid lowering therapy among patients with and without HIV infection: a cohort study. Annals of Internal Medicine 150 (5): 301-313, 2009.