The quality of evidence (I-III) is defined at the end of the "Major Recommendations" field.
Clinicians should discuss with patients the potential side effects associated with highly active antiretroviral therapy (HAART) and human immunodeficiency virus (HIV) infection.
Metabolic Complications Associated with Antiretroviral (ARV) Therapy
Disorders of Glucose Metabolism: Insulin Resistance, Impaired Glucose Tolerance, and Diabetes
Clinicians should assess fasting blood glucose before initiating HAART, 3 to 6 months after initiation, and at least annually thereafter (III).
Clinicians should administer 75 g of oral glucose (2-hr glucose tolerance test) to distinguish between impaired glucose tolerance (glucose level >140 mg/dL 2 hours after oral glucose) and diabetes (glucose level >200 mg/dL after oral glucose) in patients with repeated borderline fasting glucose values (III).
Clinicians should initiate recommended treatment and lifestyle management for HIV-infected patients with glucose intolerance or diabetes (III).
When possible, clinicians should prescribe alternatives to a protease inhibitor (PI)-based HAART regimen in patients with preexisting glucose intolerance or diabetes.
Refer to Table 1 in the original guideline document for the risk factors for type 2 diabetes mellitus in HIV-infected patients and Table 2 for the criteria for the diagnosis of diabetes mellitus.
Key Point:
If fasting blood glucose tests are not feasible, random blood glucose values may be used as an alternative screening method. Patients with random glucose consistently <100 mg/dL do not require follow-up testing. A random glucose >140 mg/dL should prompt use of a standardized diagnostic test, such as glucose tolerance test. A random plasma glucose >200 mg/dL, either repeated on a subsequent day or in the presence of unequivocal hyperglycemia, meets the threshold for the diagnosis of diabetes.
Management Considerations for Diabetes in HIV-Infected Patients
Primary care clinicians should refer diabetic patients who are not responsive to medical intervention or who have symptoms and signs of worsening diabetes to an endocrinologist and/or a diabetes specialist (III).
Primary care clinicians who lack experience in treating diabetic patients should refer patients for evaluation by a clinician experienced in managing diabetes (III).
The preferred treatment for disorders of glucose metabolism in HIV-infected patients is insulin-sensitizing agents (metformin and thiazolidinediones) (III).
Because insulin-sensitizing agents may complicate liver function, clinicians should discuss the risks and benefits with patients (III).
Metformin should not be used in patients with renal failure or a history of lactic acidosis. Thiazolidinediones should be used with caution in patients with pre-existing liver disease (I).
Switching to a PI-sparing regimen in clinically stable patients is not recommended unless standard therapies for diabetes are unsuccessful or a change is indicated because of loss of virologic suppression.
Table
Recommendations for Patients with Diabetes
|
- Patient education regarding symptoms of hyperglycemia and hypoglycemia
- Maintain glycosylated hemoglobin (HbA1c) <7%
- Annual assessment for microalbuminuria*
- Maintain triglyceride levels <150 mg/dL
- Maintain low-density lipoprotein cholesterol <100 mg/dL
- Maintain blood pressure <130/80 mmHg
- Annual retinal examination by an experienced ophthalmologist
- Annual oral health examination
- Lifestyle modification (smoking and alcohol cessation, increased exercise, weight loss, and expert nutritional counseling**)
- Annual foot examination with referral to a foot specialist (orthopedic surgeon, podiatrist, vascular surgeon, or rehabilitation) when indicated and visual foot inspection at every visit for patients at high risk for developing foot conditions (e.g., patients with prior ulcer, amputation, or diabetic neuropathy)
- Aspirin therapy for patients with evidence of macrovascular disease, a family history of coronary heart disease (CHD), or a history of cigarette smoking, and as secondary prevention after vascular events
|
For additional information, see the American Diabetes Association guidelines.
*Measurement of the albumin-to-creatinine ratio by random spot urine is preferred.
**When possible, patients should develop and maintain a nutrition plan with a Registered Dietician or Certified Diabetes Educator.
Lipid Abnormalities (Dyslipidemia)
Clinicians should monitor patients receiving ARV therapy for dyslipidemia by obtaining a fasting lipid profile before initiation of ARV therapy, between 3 and 6 months after starting or changing ARV treatment, and at least annually thereafter (I). More frequent monitoring may be indicated by the presence of persistent lipid elevation, cardiovascular risk factors, or cardiovascular symptoms (III).
If a regimen including a PI is considered for patients with preexisting hyperlipidemia or CHD, clinicians should use a PI with a low risk profile for lipid abnormalities when possible.
Clinicians should recommend lifestyle modifications, such as increased exercise, weight loss, nutrition therapy, smoking cessation, and drug addiction treatment for patients with dyslipidemia (I).
When a statin is indicated, clinicians should avoid using simvastatin and lovastatin in patients who are concurrently receiving PIs (I).
Clinicians should obtain serum liver enzymes at baseline and 4 to 6 weeks after initiating statin therapy.
Pharmacologic treatment of dyslipidemia should be guided by currently available clinical guidelines (I).
Refer to Table 4 in the original guideline document for major risk factors that modify low-density lipoprotein (LDL) goals.
Table
Low-Density lipoprotein (LDL) and Non-High-Density Lipoprotein (HDL) Cholesterol Goals and Thresholds for Therapeutic Lifestyle Changes and Drug Therapy in Different Risk Categories
|
| Risk Category |
LDL Goal (mg/dL) |
LDL Level at Which to Initiate Lifestyle Changes (mg/dL) |
LDL Level at Which to Consider Drug Therapy (mg/dL) |
Non-HDL Goal (mg/dL)* |
| Coronary heart disease (CHD) or CHD risk equivalents: diabetes mellitus, atherosclerotic disease (coronary artery disease [CAD] or stroke), or multiple risk factors (10-year risk >20%) |
<100 |
>100 |
>130 (100 to 129: drug optional)** |
<130 |
| 2+ risk factors: HDL <40 mg/dL, strong family history, age >45 years, and smoking (10-year risk >20%) |
<130 |
>130 |
10-year risk:
10 to 20%: >130
10-year risk:
<10%: >160
|
<160 |
| 0-1 risk factor*** |
<160 |
>160 |
>190
(160 to 189: LDL-lowering drug optional)
|
<190 |
Modified from the Executive Summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). Available at: www.nhlbi.nih.gov/guidelines/cholesterol/
* Non-HDL cholesterol = (total cholesterol - HDL). When LDL cannot be measured because the triglyceride level is >200 mg/dL, non-HDL cholesterol may be used as a secondary goal. The non-HDL cholesterol goal is 30 mg/dL higher than the LDL cholesterol goal.
** Some authorities recommend use of LDL-lowering drugs in this category if an LDL cholesterol level of <100 mg/dL cannot be achieved by therapeutic lifestyle changes (dietary and exercise intervention). Others prefer use of drugs that primarily modify triglycerides and HDL (e.g., nicotine acid or fibrate). Clinical judgment also may suggest deferring drug therapy in this subcategory.
*** Almost all people with 0 or 1 risk factors have a 10-year risk <10%; therefore, 10-year risk assessment in people with 0 or 1 risk factors is not necessary.
Table
Choice of Drug Therapy for Dyslipidemia in HIV-Infected Patients Receiving HAART
|
| Lipid Abnormality |
First Choice |
Second Choice (or if additional treatment is needed) |
Comments |
| Isolated high LDL |
Statin* |
Fibrate |
Start with low doses of statins, and titrate upward. Patients receiving PIs may be at increased risk of statin-induced myopathy. |
| Combined hyperlipidemia (high cholesterol and high triglycerides) |
Fibrate or statin* |
- If starting with fibrate, add statin*
- If starting with statin*, add fibrate
|
Combining statin and a fibrate may increase risk for myopathy. |
| Isolated hypertriglyceridemia |
Fibrate |
Statin* |
Combining statin and a fibrate may increase risk for myopathy. |
Adapted, with permission, from Dube MP, Sprecher D, Henry WK, et al. Preliminary guidelines for the evaluation and management of dyslipidemia in adults infected with human immunodeficiency virus and receiving antiretroviral therapy: Recommendations of the Adult AIDS Clinical Trial Group Cardiovascular Disease Focus Group. Clin Infect Dis 2000;31:1216-1224.
*Statins should be dosed at bedtime. Simvastatin and lovastatin should be avoided in patients receiving PIs.
Body Fat Changes
Clinicians should educate patients receiving ARV therapy about signs and symptoms of body fat changes.
Clinicians should recommend good nutrition and regular exercise to their patients.
Clinicians should screen patients who develop changes in body fat for depression at every visit and should provide psychological support for patients who experience mood disorders secondary to body habitus changes.
Clinicians should include an assessment for gynecomastia in the physical examination of men who are receiving HAART.
Treatment of body fat changes in the absence of metabolic complications is not routinely recommended.
Lactic Acidosis
Clinicians should monitor serum lactate levels every 4 weeks for at least 3 months in patients with lactic acidosis syndrome. Routine monitoring of serum lactate levels is not indicated in asymptomatic patients.
For patients who develop symptoms of lactic acidosis syndrome and have a confirmed, elevated arterial or venous lactate level (>5 mmol/L) with normal to decreased serum bicarbonate (<20 mmol/L), clinicians should temporarily discontinue the entire ARV regimen while a diagnostic evaluation is conducted. This evaluation should include arterial blood gas determination, serum amylase and lipase levels, and serum liver enzyme levels.
Patients who are asymptomatic and experience an unexplained decrease in serum bicarbonate level (<20 mmol/L) should be re-evaluated promptly with a venous or arterial lactate level and re-determination of the serum bicarbonate level.
If the patient has a mildly elevated lactate level (2.1 to 5.0 mmol/L), the clinician should obtain a repeat lactate level and an arterial blood gas and should re-assess the patient for the presence of symptoms associated with lactic acidosis.
If the lactate level is persistently elevated (>10 mmol/L), the arterial pH is abnormal, or the patient has become symptomatic, the clinician should discontinue ARV therapy until these conditions are resolved.
When ARV therapy is restarted, the clinician should consult with an HIV Specialist to determine an appropriate regimen.
Musculoskeletal Complications Associated with ARV Therapy
Osteopenia/Osteoporosis
Routine screening of asymptomatic HIV-infected patients without traditional risk factors for osteopenia or osteoporosis is not recommended.
Clinicians should evaluate patients who are suspected of having osteoporosis with a bone mineral density test (DEXA scan).
When a patient presents with an unexpected or unusual fracture, the clinician should promptly evaluate the patient for osteopenia/osteoporosis.
Clinicians should counsel patients at risk for osteoporosis about structuring a safe home environment.
Clinicians should initiate standard treatment for HIV-infected patients with osteopenia and/or osteoporosis.
HIV-Associated Avascular Necrosis
Clinicians should radiographically evaluate patients who present with moderate to severe bone/joint pain. The contralateral joint should also be assessed.
Clinicians should prescribe analgesic therapy for patients with avascular necrosis.
Clinicians should refer patients with avascular necrosis to an orthopedic surgeon for consultation and to physical and/or occupational therapists for ongoing therapy. Surgical treatment is the only effective therapy.
Myopathy/Myositis
Measurement of serum creatinine phosphokinase (CPK) is not routinely indicated.
HIV infection may be associated with asymptomatic elevation of CPK. In this setting, serial monitoring is not indicated.
If the patient becomes symptomatic (e.g., muscle pain or weakness), CPK should be measured.
Definitions:
Quality of Evidence for Recommendation
- Evidence from one or more properly randomized, controlled trial
- Evidence from one or more well-designed clinical trial without randomization; from cohort or case-controlled studies
- Evidence from opinions of respected authorities based on clinical experience, descriptive studies, or reports of expert committees
