HIV-associated lipodystrophy: a review of underlying mechanisms and therapeutic options

• Published in: Journal of antimicrobial chemotherapy Vol. 62; no. 4; pp. 648 - 660
• Main Authors: Mallewa, Jane E., Wilkins, Edmund, Vilar, Javier, Mallewa, Macpherson, Doran, Dominic, Back, David, Pirmohamed, Munir
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.10.2008; Oxford Publishing Limited (England)
• Subjects: adipocytokines; Anti-HIV Agents - adverse effects; Antibiotics. Antiinfectious agents. Antiparasitic agents; antiretroviral therapy; Antiretroviral Therapy, Highly Active - adverse effects; Biological and medical sciences; Dermatology; HIV; HIV Infections - complications; HIV-Associated Lipodystrophy Syndrome - chemically induced; HIV-Associated Lipodystrophy Syndrome - therapy; Human immunodeficiency virus; Human viral diseases; Humans; Immunodeficiencies; Immunodeficiencies. Immunoglobulinopathies; Immunopathology; Infectious diseases; Lipids; Medical sciences; Medical treatment; Metabolism; nucleoside reverse transcriptase inhibitors; Pharmacology. Drug treatments; protease inhibitors; Skin involvement in other diseases. Miscellaneous. General aspects; Toxicity; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Virology; protease inhibitors; adipocytokines; nucleoside reverse transcriptase inhibitors; antiretroviral therapy; Skin disease; Antiretroviral agent; Review; Reverse transcriptase inhibitor; Antiviral; Nucleoside; Mechanism of action; Immunopathology; Retroviridae; AIDS; Adipokine; Immune deficiency; Lentivirus; Infection; Virus; Chemotherapy; Treatment; Viral disease; Lipodystrophy; Adipose tissue disorders; Human immunodeficiency virus; Protease inhibitor; Bibliographic review
• ISSN: 0305-7453; 1460-2091
• DOI: 10.1093/jac/dkn251

Lipodystrophy (LD) is a common adverse effect of HIV treatment with highly active antiretroviral therapy, which comprises morphological and metabolic changes. The underlying mechanisms for LD are thought to be due to mitochondrial toxicity and insulin resistance, which results from derangements in levels of adipose tissue-derived proteins (adipocytokines) that are actively involved in energy homeostasis. Several management strategies for combating this syndrome are available, but they all have limitations. They include: switching from thymidine analogues to tenofovir or abacavir in lipoatrophy, or switching from protease inhibitors associated with hyperlipidaemia to a protease-sparing option; injection into the face with either biodegradable fillers such as poly-l-lactic acid and hyaluronic acid (a temporary measure requiring re-treatment) or permanent fillers such as bio-alcamid (with the risk of foreign body reaction or granuloma formation); and structured treatment interruption with the risk of loss of virological control and disease progression. There is therefore a need to explore alternative therapeutic options. Some new approaches including adipocytokines, uridine supplementation, glitazones, growth hormone (or growth hormone-releasing hormone analogues), metformin and statins (used alone or in combination) merit further investigation.