Effectiveness of Statins among HIV Positive People on Antiretroviral Therapy

		SUMMARY: Atorvastatin (Lipitor) and rosuvastatin (Crestor) may be the best choices for HIV positive people who need a statin drug to control elevated cholesterol, according to a study report in the December 28, 2010 advance online edition of Clinical Infectious Diseases. Researchers found that these 2 medications produced greater decreases in total and LDL cholesterol, with about the same degree of toxicity as pravastatin (Pravachol).

By Liz Highleyman

Abnormal blood fat levels, or dyslipidemia, are common among people with HIV and are associated with certain antiretroviral drugs. Lifestyle changes such as improved diet and more exercise can help lower harmful low-density lipoprotein (LDL) "bad" cholesterol and raise protective high-density lipoprotein (HDL) "good" cholesterol, but such measures may not be adequate, necessitating use of statins (also known as HMG CoA reductase inhibitors).

In an effort to learn more about the comparative effectiveness of this class of drugs in HIV positive people, researchers from the University of Washington and University of Alabama compared the effectiveness and toxicity of different statins among HIV patients in clinical care.

This retrospective analysis included 700 HIV positive individuals starting their first treatment with statins at 2 large HIV clinics between 2000 and 2008. Most (86%) were men, the average age was 43 years, and the mean nadir (lowest-ever) CD4 T-cell count was 182 cells/mm3.

Researchers looked at changes in blood lipid levels during statin therapy, whether patients achieved National Cholesterol Education Program (NCEP) goals for LDL and HDL levels, and drug-related adverse events or toxicities.

Results

	The most commonly prescribed statins were:
	Atorvastatin: 303 patients, 43%; Pravastatin: 280 patients, 40%; Rosuvastatin: 95 patients, 14%; Simvastatin (Zocor): 14 patients, 2%; Fluvastatin (Lescol): 5 patients, <1%; Lovastatin (Mevacor): 3 patients, <1%.
	1 year after starting statin therapy, patients who received atorvastatin or rosuvastatin experienced significantly larger blood lipid decreases compared with those taking pravastatin:
	Total cholesterol: 39, 43, and 25 mg/dL, respectively; LDL cholesterol: 26, 23, and 12 mg/dL, respectively; Non-HDL cholesterol: 39, 47, and 26 mg/dL, respectively; Triglycerides: 60, 83, and 24 mg/dL, respectively.
	People who used atorvastatin or rosuvastatin were also significantly more likely to reach NCEP goals for LDL than those taking pravastatin (odds ratio [OR] 2.1, or about twice as likely).
	The likelihood of reaching NCEP goals for non-HDL was higher for rosuvastatin, but not for atorvastatin, relative to pravastatin (OR 2.3 and 1.5, respectively).
	Toxicity rates were similar for all 3 statins:
	7.3% for atorvastatin; 6.1% for pravastatin; 5.3% for rosuvastatin.
	Among the 44 patients who experienced toxicities, 15 -- or just 2.2% of all study participants -- had potentially serious adverse events.
	Elevated creatine phosphokinase (CPK), with or without a decline in kidney function, was the most common potentially serious toxicity, followed by elevated liver enzymes.

Based on these data, the study authors concluded, "Our findings suggest that atorvastatin and rosuvastatin are preferable to pravastatin for treatment of HIV-infected patients with dyslipidemia, due to greater declines in total cholesterol, LDL [cholesterol], and non-HDL [cholesterol], with similar lower toxicity rates."

"Results from studies of the effectiveness and toxicity of statins among HIV-infected individuals may differ from results for the general population for several reasons," the researchers explained in their discussion. "The patterns of dyslipidemia commonly seen among HIV-infected individuals differ from those in persons without HIV infection and may be less responsive to treatment. Second, drug interactions between statins and antiretroviral medications may impact the metabolism, effectiveness, and toxicity risk associated with particular statins."

Guidelines from the Infectious Disease Society of America and the Adult AIDS Clinical Trials Group recommend atorvastatin or pravastatin for HIV positive people -- in part because these drugs were thought to be less likely to interact with antiretroviral drugs metabolized by the cytochrome P450 3A4 enzyme -- but the new findings "suggest that the lipid-lowering effectiveness of pravastatin was significantly less than that of rosuvastatin or atorvastatin."

"We found a nonsignificant increase in HDL [cholesterol] levels at 12 months among those receiving rosuvastatin," they added. "HDL [cholesterol] may increase as much as 10% with rosuvastatin among those without HIV. Our results are consistent with the idea that combined (mixed) dyslipidemia in HIV-infected patients may be more difficult to treat and thus raises the question of whether combination therapy with additional lipid-lowering agents may be needed."

Investigator affiliations: Department of Medicine, University of Washington, Seattle, WA; Department of Medicine, University of Alabama at Birmingham, Birmingham, AL.

1/11/11

Reference
S Singh, JH Willig, MJ Mugavero, and others. Comparative Effectiveness and Toxicity of Statins Among HIV-Infected Patients. Clinical Infectious Diseases (Free full text). December 28, 2010 (Epub ahead of print).