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atherogenesis.[906] In this syndrome, there is moderate hypercholesterolemia and marked
hypertriglyceridemia along with insulin resistance and glucose intolerance typical for diabetes
mellitus. These are findings characteristic of metabolic syndrome. Metabolic syndrome is
defined by the presence of 3 or more of the following: a waist circumference >102 cm for men
and >88 cm for women; a fasting triglyceride >150 mg/dL; an HDL cholesterol of <40 mg/dL in
men or <50 mg/dL in women; a blood pressure >130/85 mm Hg; a fasting glucose >110 mg/dL.
Lipid-lowering strategies with use of pharmacologic therapies such as fibric acid derivatives,
along with insulin agonists including metformin and thiazolidinediones, can be employed.[907]
Atherosclerotic vascular disease, beginning with endothelial dysfunction similar to that
seen with type 2 diabetes mellitus, has been reported with use of ART with protease inhibitors,
and this may occur without metabolic markers.[908]. Additional mechanisms for protease
inhibitor associated atherosclerosis include proteasome inhibition, increased CD36 expression in
macrophages, inhibition of lipoprotein lipase-mediated lipolysis, decreased adiponectin levels,
and dysregulation of the NF-[kappa]B pathway.[909] In addition, HIV has been shown to
directly infect arterial smooth muscle cells, leading to proliferation, and this may promote
atherosclerotic plaque formation.[910] There are increased levels of circulating adhesion
molecules such as ICAM-1 and VCAM-1. Endothelial dysfunction as measured by brachial
artery flow mediated vasodilation (FMD) is abnormal in HIV infected persons.[902]
Smoking as an additional risk factor for atherosclerotic heart disease is seen in these
patients.[911] Peripheral vascular disease may be more prevalent in persons with HIV infection,
occurring 20 years earlier than in the general population. Age, diabetes, smoking, and low CD4
counts appear to be independent predictors in persons with HIV infection.[912] Peripheral
vascular atherosclerosis, however, may not be associated with lipodystrophy.[913]
Acute myocardial infarction can occur, and persons with HIV infection have such an
event at a younger age than the general population. However, the absolute risk for developing
coronary events remains low compared with that of a HIV-negative matched population, with
relative risk of 1.16 per year. Management of antiretroviral related metabolic disorders has
gradually improved over time. There is a 6-fold increase in prevalence for peripheral vascular
disease with HIV infection, compared to adults seronegative for HIV.[914]

VASCULITIS.-- Vasculitis associated with HIV infection may result the effects of HIV
proliferation and inflammatory response, or from opportunistic infections. About 1% or less of
persons infected with HIV may develop vasculitis. The most common pattern of vasculitis
resembles polyarteritis nodosa, (PAN) and involves medium to small vessels. It differs from
classic PAN because of absence of waxing and waning course, absence of association with
hepatitis B viral infection, and lack of multisystem organ involvement. The most common areas
of involvement are skin, peripheral nerve, and muscle, followed by central nervous system,
lungs, gastrointestinal tract, and kidneys. Hypersensitivity vasculitis involves medium to small
sized vessels, most often in the skin and accompanied by palpable purpura. It may also result
from infections with CMV, Epstein-Barr virus, or hepatitis B virus.[915,916]
Additional vasculitic patterns reported include cryoglobulinemic vasculitis,
granulomatosis with polyangiitis, Kawasaki-like syndrome, giant cell arteritis, primary angiitis
of the central nervous system, and erythema elevatum diutinum. Primary angiitis is a rare
condition characterized by a granulomatous inflammatory infiltrate, often with multinucleated
giant cells most often affecting small arteries and veins of the leptomeninges; it is associated
with a high mortality rate. Non-necrotizing vasculitis may affect a third of HIV-infected