Complications of human immunodeficiency virus

I. Problem/Condition.

In recent years, a large body of data has been published that suggests an increased burden of cardiovascular disease in HIV-infected individuals. HIV has been independently associated with premature atherosclerosis both before and after initiation of antiretroviral therapy (ART).

The pathophysiology of this is likely multifactorial and involves: 1) the atherogenic nature of the virus, 2) the higher than usual prevalence of traditional risk factors in HIV-infected populations (smoking, intravenous drug use [IVDU]), 3) dyslipidemia and diabetes mellitus (DM) caused by protease inhibitors (PIs), and 4) direct atherogenic effect of the PIs and select nucleoside reverse-transcriptase inhibitors. Higher levels of pro-inflammatory cytokines during active viral replication also increase the risk of cardiovascular disease.

II. Diagnostic Approach

A. What is the differential diagnosis for this problem?

The differential diagnosis for a HIV-infected patient who presents with complaints suggestive of a myocardial infarction is similar to that of a immunocompetent patient. Other cardiovascular concerns include:

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ART can lead to metabolic changes, such as dyslipidemia, which is treatable with statins.

Other ART-associated metabolic changes that can lead to increased cardiovascular risk are insulin resistance and body fat redistribution.

B. Describe a diagnostic approach/method to the patient with this problem

The diagnostic approach depends on a careful history and physical examination, and is essentially the same as for an immunocompetent patient. A recent CD4 count (and preferably a recent trend) and antiretroviral treatment history can help determine patients’ risk for coronary artery disease (CAD), peripheral arterial disease (PAD), and microvascular occlusive disease.

1. Historical information important in the diagnosis of this problem.

Important questions to ask include the following:

Careful history and timing of chief complaint.

Associated symptoms – there may be more than one diagnosis.

History of HAART and adherence – presentation may be related to drug side effects.

CD4 count and history – previous AIDS-defining illness or CD4 count less than 200 predisposes to more serious infection even if counts are currently above 200.

Careful social history – IVDU increases risk for bacterial pneumonia; TB and viral hepatitis; smoking increases the risk for lung cancer and heart disease.

2. Physical Examination maneuvers that are likely to be useful in diagnosing the cause of this problem.

A thorough cardiovascular exam is necessary, including cardiac exam for murmurs, distant heart sounds, elevated jugular venous distention, lower extremity exam for edema, and pulmonary exam for rales. In the scope of focusing on a HIV-infected individual presenting to a hospital setting, it is of utmost importance to perform a thorough physical examination, including skin, oropharynx, and abdominal exam regardless of the chief complaint.

3. Laboratory, radiographic and other tests that are likely to be useful in diagnosing the cause of this problem.

Cardiovascular symptoms

HIV-infected individuals should be evaluated in exactly the same way as patients without immunodeficiency in the face of cardiac symptoms, including basic labs, ECGs and troponins. Please refer to the chapter on CAD. The important thing to keep in mind is that this is likely a high-risk population for development of coronary artery disease.

C. Criteria for Diagnosing Each Diagnosis in the Method Above.

Please see disease-specific chapters for exact diagnostic criteria.

D. Over-utilized or “wasted” diagnostic tests associated with the evaluation of this problem.

This is a population of patients, especially the ones with severe immunocompromise, in which it is worthwhile to cast a wide net for diagnostic purposes. HIV-infected patients often have extended hospital stays, and undergo multiple costly tests and procedures. This is hard to avoid because of the high morbidity and mortality associated with complications of this disease.

The utility of obtaining a CD4 count in the setting of acute illness is questionable. There is a body of literature showing that patients with acute illness in the intensive care unit (ICU) have falsely depressed CD4 counts even if they do not have HIV infection. This likely applies to HIV patients with acute illness; the CD4 count obtained will be falsely low leading to unnecessary investigations. Thus, if a patient has a recent CD4 count from an outpatient clinic, it is appropriate to assume those are accurate and forego obtaining a new confounding lab in the hospital.

That said, patients with a new diagnosis and no previous CD4 count should have one obtained on presentation.

Also, viral loads obtained in the hospital are often seen, but there are usually no therapeutic decisions that depend on them.

III. Management while the Diagnostic Process is Proceeding

A. Management of complications of human immunodeficiency virus.

The severity of presenting illness will dictate the amount of resuscitative effort. After stabilization, a focused investigation should be expedited based on presenting symptoms.

For management of urgent cardiac conditions, please see disease-specific chapters. Patients with HIV presenting with cardiovascular complaints should be managed the same way as their immunocompetent counterparts. Before initiation of statins, it is important to consider drug interactions with ART.

For long-term management, viral suppression with ART may reduce CVD events.

IV. What's the evidence?

Calza, L. “Myocardial infarction risk in HIV-infected patients: epidemiology, pathogenesis, and clinical management”. AIDS. vol. 24. 2010. pp. 789-802.

Farrugia, PM. “Human immunodeficiency virus and atherosclerosis”. Cardiol Rev. vol. 17. 2009. pp. 211-5.

Hemkens, LG, Bucher, HC. “HIV infection and cardiovascular disease”. European Heart Journal. 2014.

Lipshultz, SE, Mas, CM, Henkel, JM, Franco, VI, Fisher, SD, Miller, TL. “HAART to heart: highly active antiretroviral therapy and the risk of cardiovascular disease in HIV-infected or exposed children and adults”. Expert Rev Anti Infect Ther. vol. 10. 2012 Jun. pp. 661-74.