Ward 86 Management Recommendations
updated April 2016
Contributors: Vivek Jain, MD, MAS
Monica Gandhi, MD
Susa Coffey, MD
Mark A. Jacobson, MD
Cardiovascular Disease Prevention
HIV-infected patients are at increased risk of myocardial infarction and stroke due to the accelerated atherosclerosis that often complicates HIV disease, even among patients who have been virologically suppressed by antiretroviral therapy (ART) for many years. Thus, a high priority in medical management of HIV disease is to eliminate or mitigate any reversible risk factors for cardiovascular disease (CVD) such as smoking, hyperlipidemia, diabetes mellitus, and hypertension.
Multiple studies have documented that HIV patients have higher rates of cardiovascular events and cardiovascular mortality than age-matched controls.(1) In one study, ultrasound-determined intima-media thickness (IMT) of the carotid artery (a marker of an increased risk of vascular events used as a surrogate end point for cardiovascular outcomes) was increased two-fold in HIV-infected patients compared with controls over 2 years of follow-up.(2) In a cross-sectional study, the association of HIV infection with increased carotid IMT was similar to that of smoking, and the difference remained significant even after adjusting for demographic factors, cardiovascular disease risk factors, and C-reactive protein levels.(3)
We recommend all HIV patients have fasting serum lipids tested yearly and 3 months after initiating any antiretroviral drug that can cause hyperlipidemia as an adverse effect (ie, regimens containing efavirenz or protease inhibitors [PIs]). The lipid test should include LDL cholesterol, HDL cholesterol, and triglycerides.
Treatment for Hyperlipidemia
Switching to a nonlipogenic ART regimen: We recommend that any patient taking efavirenz or PIs who has a serum LDL >130 mg/dL (or >100 mg/dL if the patient has known atherosclerosis or a history of stroke or myocardial infarction) switch to an ART regimen that eliminates efavirenz and PIs unless there are no other tolerable or efficacious ART options.
There are now many safe, effective alternatives to efavirenz or PIs as the anchoring agent in an antiretroviral regimen, and there is abundant evidence that, in the absence of documented resistance to the new anchoring agent (ie, by genotype or a history of virologic failure on the new agent), switching is safe and effective in reducing LDL levels. Nonlipogenic drugs that can be used in place of efavirenz or PIs include any of the integrase inhibitors, etravirine, and rilpivirine.
- Patients not receiving efavirenz or PIs and patients who cannot be safely switched to a nonlipogenic ART regimen because of risk of virologic failure or treatment intolerance: Patients in this category who have an LDL >130 mg/dL should receive statin therapy, as should those who have an LDL >100 mg/dL and 2 or more risk factors besides HIV for cardiovascular disease (eg, smoking, positive family history, diabetes, hypertension, obesity, age >50 years).
Numerous trials have demonstrated that statin therapy can reduce the relative risk of a CVD event by 20-30% in patients with LDL levels >100 mg/dL. Because the benefit of statin treatment is proportional to the underlying risk of having such an event, recent guidelines have focused on determining a patient's underlying CVD event risk, rather than targeting a specific LDL threshold, as a trigger for initiating statin therapy. In November 2013, the American Heart Association and American College of Cardiology (AHA/ACC) recommended that statins be administered when a patient's 10-year risk of a CVD event can be calculated to be >7.5% and to consider statins when the 10-year risk is 5-7.5%.(4) However, subsequent analyses have reported that the risk calculator recommended by the AHA/ACC systematically overestimates risk by 75-150%. An additional problem with using the AHA/ACC guidelines is that none of the large, randomized, controlled trials of statin therapy that demonstrated efficacy of statin primary prevention used risk prediction scores for trial entry. Finally, trials of primary prevention of cardiovascular disease in general populations do not factor in HIV disease as a risk factor for atherosclerosis. Taking all this into consideration, in HIV-infected patients we currently recommend using the LDL threshold values as indicated above to determine who should receive statin therapy, with the specific threshold choice indicated by the absence or presence of additional risk factors for cardiovascular disease besides HIV.
All patients with a history of myocardial infarction, stroke, or symptomatic peripheral vascular disease, or evidence of clinically significant coronary artery stenosis should receive statin therapy.
Statin choice and dosage: Interactions with PIs or nonnucleoside reverse transcriptase inhibitors (NNRTIs) can respectively inhibit or induce statin metabolism, thus raising or lowering plasma levels of some statins and possibly causing toxic or subtherapeutic statin levels. Only 4 currently available statins should be prescribed concomitantly with PIs or NNRTIs.
Atorvastatin: Begin with a dosage of 10-20 mg PO daily (10 mg for those receiving PIs); monitor LDL every 8-12 weeks, increasing statin dosage until LDL has reached target levels (<130 mg/dL or <100 mg/dL) or up to a maximum dosage of 80 mg daily. Concomitant nevirapine, efavirenz, or etravirine can lower statin levels and thus require increasing the statin dosage, though 80 mg still should be the maximum dosage. Etravirine may increase active metabolite levels of atorvastatin, thus increasing the risk of toxicity.
Pravastatin: Begin with a dosage of 20-40 mg PO daily (10 mg for patients receiving PIs); monitor LDL every 8-12 weeks, increasing statin dosage until LDL has reached target levels (<130 mg/dL or <100 mg/dL) or up to a maximum dosage of 80 mg daily. Efavirenz is the only NNRTI that has been reported to lower pravastatin serum levels.
Rosuvastatin: Begin with a dosage of 5-10 mg PO daily (5 mg for patients receiving PIs); monitor LDL every 8-12 weeks, increasing statin dosage until LDL has reached target levels (<130 mg/dL or <100 mg/dL) or up to a maximum dosage of 40 mg daily. No drug interactions with NNRTIs have been reported.
Pitavastatin: This new statin does not have significant drug interactions with PIs or NNRTIs. Begin with dosage of 2 mg PO daily, 1 mg daily if renal impairment is present.
- Other cholesterol lowering medications: Although other agents have efficacy in lowering LDL levels (eg, ezetimibe, niacin, cholestyramine), none have been shown in randomized trials to reduce CVD event end points. We do not recommend use of these agents. Recent data suggest that niacin actually may increase mortality.(5)
Patients receiving a PI or efavirenz who have a serum triglyceride level >500 mg/dL despite dietary modifications should be switched, if possible, to an alternative ART regimen that eliminates PIs and efavirenz or should be treated with a fibrate agent (fenofibrate or gemfibrozil).
- A growing body of evidence now links severe hypertriglyceridemia (>500 mg/dL) with risk of cardiovascular disease. As noted above, there are many nonlipogenic drugs that can be used in place of PIs, including integrase inhibitors, etravirine, or rilpivirine.
Fibrate choice and dosage: We prefer fenofibrate (150-160 mg micronized fenofibrate PO daily) over gemfibrozil because of its reduced rate of muscle toxicity. Patients receiving combined fibrate and statin therapy should have serum creatine kinase checked at baseline and at least every 6 months during follow-up.
- Althoff KN, McGinnis KA, Wyatt CM, et al; Veterans Aging Cohort Study. Comparison of risk and age at diagnosis of myocardial infarction, end-stage renal disease, and non-AIDS-defining cancer in HIV-infected vs uninfected adults. Clin Infect Dis. 2014 Oct 30.
- Hsue PY, Scherzer R, Hunt PW, et al. Carotid intima-media thickness progression in HIV-infected adults occurs preferentially at the carotid bifurcation and is predicted by inflammation. J Am Heart Assoc. 2012 Apr;1(2). pii: jah3-e000422.
- Grunfeld C, Delaney JA, Wanke C, et al. Preclinical atherosclerosis due to HIV infection: carotid intima-medial thickness measurements from the FRAM study. AIDS. 2009 Sep 10;23(14):1841-9.
- Stone NJ, Robinson JG, Lichtenstein AH, et al. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014 Jun 24;129(25 Suppl 2):S1-45.
- Lloyd-Jones DM. Niacin and HDL cholesterol--time to face facts. N Engl J Med. 2014 Jul 17;371(3):271-3.