retinoic-acid binding protein type 1 may prevent a cascade of molecular events leading to peripheral adipocyte differentiation and apoptosis. An alternative suggested mechanism is that PI therapy inhibits adipogenesis by a process involving sterol regulatory element binding proteins (SREBPs), which play a central role in cellular lipid homeostasis [21]. Differences in the metabolic activity of central, dorso-cervical and peripheral adipocytes have been proposed. Thus, the impaired fat storage and hyperlipidemia associated with protease inhibitor treatment may lead to preferential central accumulation of fat. A link between PI therapy and altered apolipoprotein (B and C-III) synthesis has also been postulated [22].

had higher prevalence of buffalo hump and breast enlargement, but a lower prevalence of facial and gluteal fat loss compared with underweight patients (BMI < 20 kg/m2) [25]. Older people tend to have greater body fat mass, particularly intra-abdominal fat, which may contribute to the body fat changes seen in HIV-associated lipodystrophy [26].

63.6 Female Sex

Trunk obesity rather than subcutaneous fat wasting appears to be more common in women than in men [27], although prospective studies are required to evaluate whether there are true differences between the sexes.

63.3.5Non-Nucleoside Reverse Transcription Inhibitors

Mitochondrial toxicity associated with nonnucleoside reverse transcription inhibitors (NRTIs) has also been well established and is thought to contribute to the fat redistribution syndrome seen in patients with HIV infection [23, 24]. It has been suggested that the pattern of lipodystrophy varies with drug therapy: NRTIs are associated with lipoatrophy alone, while NRTI combined with PI therapy is associated with lipoatrophy and lipohypertrophy. However, the wide variety of drug combinations used make it difficult to identify risk associated with particular drugs.

63.4 HIV Infection

The development of HIV lipodystrophy has been positively associated with the duration of HIV infection, negatively associated with previous HIV viral load and both positively and negatively associated with blood CD4 lymphocyte counts in various studies [16].

63.5Nutritional Status, Age, and Adiposity

Body adiposity before receiving antiretroviral therapy may also affect features of lipodystrophy. In one crosssectional study, patients with BMI greater than 28 kg/m2

63.7 Cytokines

There is an association between lipodystrophy and levels of serum inflammatory factors. One study analysed the mRNA expression of adipocytokines and transcriptional factors in fat samples from 26 patients with peripheral lipoatrophy [28]. The patients’ fat showed higher values of apoptosis, fibrosis, vessel density and macrophage infiltration than controls, together with lower adiponectin and leptin mRNA levels and higher interleukin (IL)-6 and tumour necrosis factor (TNF) alpha mRNA levels. Elevated levels of the soluble type 2 tumour necrosis factor-alpha receptor has been linked with insulin resistance associated with lipodystrophy.

C-peptide has been shown to be the strongest metabolic predictor of future lipodystrophy severity in patients receiving combined NRTI and protease inhibitor therapy [29].

63.8 Management

63.8.1Nonsurgical Treatment of HIV Facial Lipoatrophy

No specific medical treatment exists for HIV-associated lipodystrophy. The use of recombinant growth hormone can be beneficial in patients with visceral abdominal fat or dorso-cervical fat pad; however, it is not recommended