63.1HIV-Associated Lipodystrophy Syndrome

Although the survival of HIV-infected patients has improved dramatically due to highly active antiretroviral therapy (HAART), prolonged HAART is associated with side effects including HIV-associated lipodystrophy. This is a syndrome consisting of morphological changes (central fat accumulation and peripheral fat atrophy) and metabolic changes (hyperlipidemia and insulin resistance) which has been increasingly reported in patients since 1998 [1]. The consequence of body fat changes is social stigmatisation that may negatively affect the quality of life of patients with HIV disease and may pose a barrier to treatment and reduce medical adherence.

63.2 Prevalence

From the era of HAART (Highly Active Antiretroviral Therapy), a spectrum of changes in body fat has been reported to occur in 20–80% of subjects receiving these therapies [2–6]. Variations in the reported

prevalence rates are related to a variety of many factors, including age, genetics, HIV medications and case definition.

63.3 Clinical Features

63.3.1 Morphological Changes

Changes in body fat distribution are characteristic of HIV-associated lipodystrophy. The most prominent clinical sign is a loss of subcutaneous fat in the face and extremities. Facial lipoatrophy has been attributed to the loss of buccal, parotid and pre-auricular fat pads [7], and may be accentuated by parotid hypertrophy in some patients. Adipose tissue loss from the peripheral regions occasionally leads to prominent veins resembling varicosities. Some patients have concomitant deposition of excess adipose tissue around the neck (Fig. 63.1), over the dorso-cervical spine (Fig. 63.2),

Fig. 63.3 Excess deposition of fat of the upper torso and intraabdominal region

upper torso and intra-abdominal region (Fig. 63.3) [8, 9]. Dorso-cervical fat accumulation can be disfiguring and is associated with the development of neck pain and sleep apnea [10]. This can also be associated with fat accumulation around the occipital region. Breast enlargement has been reported in both sexes, although it is unclear whether this is due to excess subcutaneous fat, glandular hypertrophy, or both [11, 12].

On body shape changes alone, three different patterns of lipodystrophy have been described: some patients have only lipohypertrophy, some have only lipoatrophy and some patients exhibit a mixed clinical presentation. Because no uniform morphologic changes occur with HIV lipodystrophy, there is now accumulating evidence that lipoatrophy, central

63.3.2 Metabolic Changes

Frequently, complex metabolic alterations are associated with the described body shape alterations. These include peripheral and hepatic insulin resistance, impaired glucose tolerance, type 2 diabetes, hypertriglyceridemia, hypercholesterolemia, increased free fatty acids and reduced high-density lipoproteins [18]. The prevalence of insulin resistance and glucose tolerance is reported in the literature at 20–50% depending on study design and measurement methods [19, 20].

63.3.3 Pathogenesis

The reasons for fat depletion and accumulation in HIVinfected patients receiving antiretroviral therapy remain unclear. The pathogenesis of HIV lipodystrophy is complex and the aetiology is likely to be multifactorial. Studies published provide evidence for two assumptions: first, lipoatrophy and lipoaccumulation result from divergent mechanisms. Second, the various classes of antiretroviral drugs contribute to the lipodystrophy syndrome by different and probably overlapping mechanisms.

63.3.4 Protease Inhibitors

Many studies have suggested a link between the use of protease inhibitors and the development of lipodystrophy. Protease-inhibitor (PI) binding of cytoplasmic