The IDSA and the ACTG recently updated their guidelines for management of dyslipedemia, which were published as “Guidelines for the Evaluation and Management of Dyslipidemia in Human Immunodeficiency Virus (HIV)-Infected Adults Receiving Antiretroviral Therapy: Recommendations of the HIV Medicine Association of the Infectious Disease Society of America and the Adult AIDS Clinical Trials Group” [Dube MP, et al. Clin Infect Dis. 2003 Sep 1;37(5):613-27]. Hyperlipidemia is now recognized as a relatively common complication of HAART. The ACTG Cardiovascular Disease Focus Group addressed this issue with preliminary guidelines for evaluation and management of dyslipidemia in 2000 [Dube MP, et al. Clin Infect Dis. 2000 Nov;31(5):1216-24]. Since that time there has been substantial progress in the field as well as new guidelines from the National Cholesterol Education Program (NCEP) [Expert Panel, JAMA. 2001 May 16;285(19):2486-97]. The following represents a summary of the updated guidelines from the Cardiovascular Disease Focus Group. The major risk factors (exclusive of low density lipoprotein-cholesterol [LDL-C]) that modify LDL-C l goals are:

• Cigarette smoking
• Hypertension: BP >140 or antihypertensive treatment)
• Low high density lipoprotein cholesterol (HDL-C): <40 mg/dL
• Family history: Male first degree relative <55 years or female first degree <65 years
• Age: Men >45 years, women >55 years

Goal of Therapy

The major target is LDL-C based on the more recent NCEP guidelines. LDL-C goals and recommendation for when to initiate intervention are summarized below. These recommendations are based on associated conditions that confer independent risks derived from the Framingham Heart Study.

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Screening

Patients should be tested for total cholesterol, HDL-C and triglyceride levels after a >8 (preferably 12) hour fast at baseline, at 3-6 months after initiation of therapy, and then annually. The LDL-C and non-HDL-C levels are calculated using these results. Non-HDL-C is calculated as total cholesterol minus HDL-C, and is an alternative measure of “bad” cholesterol. The non-HDL-C goals are 30 mg/dL higher than the LDC-C levels in the table below. Levels should be measured more frequently if they are elevated or if drug therapy is initiated.

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Therapy

• Non-drug therapy: Lifestyle changes including dietary change, smoking cessation, and exercise. Treatment of high blood pressure and diabetes are also the first line of therapy.
• If life style changes are ineffective in modifying dyslipedemia, initiation of drug therapy is recommended (see “Drug Therapy for Modifying Dyslipedemia” table below).
• Sequencing: Initiate non-drug therapy first unless there are extreme elevations (e.g. LDL-C >220 mg/dL and/or triglyceride >2000 mg/dL or >1000 mg/dL plus a history of pancreatitis).
• Switching antiretroviral therapy: The following changes may be considered
  PI– NVP or ABC: Improves total cholesterol and triglyceride
  PI– EFV: is less effective than switching to NVP or ABC
  d4T– ABC: the effect upon lipids is inconclusive

Additional references for drug interactions:

• Pharmacokinetic interactions between protease inhibitors and statins in HIV seronegative volunteers: ACTG Study A5047 [Fichtenbaum CJ, et al. AIDS 2002 Mar 8;16(4):569-77]
• Pravastatin 40 mg qd Does Not Alter Protease Inhibitor (PI) Exposure or Virological Efficacy Over 24 Weeks Therapy [Moyle GJ, et al. Abstract 446W 9th CROI 2002]

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Comment on the Guidelines

Many of the recommendations are based on the National Cholesterol Education Program Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults [JAMA. 2001 May 16;285(19):2486-97].

This particularly applies to risk assessment, the goals for LDL-cholesterol levels and the approach to drug therapy. Factors that are somewhat unique to persons with HIV infection are the influence of HAART on lipids, the recommendations for screening in patients receiving this therapy, several issues regarding therapeutic intervention, and drug interactions between statins and protease inhibitors. With regard to the recommended drugs, the statins that are favored for concurrent use with PIs include pravastatin, atorvastatin and fluvastatin. Unfortunately, their recommendations appear to have preceded the FDA approval of rosuvastatin, which is of particular interest because of its potency and lack of effect on the cytochrome P450 metabolic pathway. The recommendations also preceded the approval of atazanavir, which does not increase lipid levels.

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