New and emerging agents in the management of lipodystrophy in HIV-infected patients

Abstract

Lipodystrophy remains a major long-term complication in human immunodeficiency virus-infected patients under antiretroviral (ARV) therapy. Patients may present with lipoatrophy or lipohypertrophy or both. The choice of treatments to improve fat redistribution depends on the form of lipodystrophy and its duration. Measures known to improve lipoatrophy are switches in ARV therapy (stavudine or zidovudine to abacavir or tenofovir) and filling interventions. Pioglitazone may be added to these measures, although any benefits appear small. Uridine and leptin were found to be disappointing so far. Regarding lipohypertrophy, diet and exercise, recombinant human growth hormone, and metformin may reduce visceral fat, but may worsen subcutaneous lipoatrophy. Surgical therapy may be required. Attractive pharmacologic treatments include growth hormone-releasing factor and leptin. Adiponectin and adiponectin receptors are promising therapeutic targets to explore.

Highly Active Antiretroviral Therapy-Associated Metabolic Syndrome and Lipodystrophy: Pathophysiology and Current Therapeutic Interventions

“…PIs have been shown to suppress adipocyte differentiation [9,[22][23][24]. The catalytic site of HIV-protease, to which PIs bind shares approximately 63% of 12-amino acid sequence homology with a region incorporating a lipid binding domain in the low-density lipoprotein receptor-related protein (LRP) and 58% with a C-terminal region of the cytoplasmic retinoic acid binding protein type 1 (CRABP-1) [15,17], respectively.…”

“…These morphological changes are irreversible and non-progressive upon withdrawal of treatment but contribute significantly to social stigma [13,21]. Some patients with dorsocervical fat pads have restricted neck mobility, women with breast enlargement may experience chronic back pain, while men with gynecomastia feel socially prejudiced [9]. This may lead to poor adherence to ART, low self-esteem and reduced quality of life in the affected patients [9,13,21].…”

“…Some patients with dorsocervical fat pads have restricted neck mobility, women with breast enlargement may experience chronic back pain, while men with gynecomastia feel socially prejudiced [9]. This may lead to poor adherence to ART, low self-esteem and reduced quality of life in the affected patients [9,13,21]. These conditions if not carefully managed may ultimately predispose a significant number of patients to increased risks of metabolic syndrome, diabetes and cardiovascular diseases.…”

“…Lipodystrophy is defined by the loss of peripheral subcutaneous fat (lipoatrophy) and central fat accumulation (lipohypertrophy), which may occur separately or co-exist in the same patient [8,9]. Lipoatrophy is associated with the loss of subcutaneous fat mainly in the face, arms, buttocks and lower limbs whereas lipohypertrophy is characterised by fat accumulation in the adipose tissues at the back of the neck "buffalo hump" or dorsocervical region, abdominal adiposity and mammary hypertrophy/gynecomastia [8][9][10].…”

“…Lipoatrophy is associated with the loss of subcutaneous fat mainly in the face, arms, buttocks and lower limbs whereas lipohypertrophy is characterised by fat accumulation in the adipose tissues at the back of the neck "buffalo hump" or dorsocervical region, abdominal adiposity and mammary hypertrophy/gynecomastia [8][9][10]. The etiology of lipodystrophy syndrome is poorly understood but the incidence is estimated at 2-60% and 30% in adults and children on HAART, respectively [9,[11][12][13].…”