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

Abstract

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.

Prevalence of and Clinical Factors Associated with Lipoatrophy in HIV-Infected Koreans Receiving Highly Active Antiretroviral Therapy

“…In general, lipoatrophy is clearly linked with HAART, and is especially strongly associated with the use of d4T, and is more likely to improve upon treatment regimen change (Grinspoon and Carr 2005;Pujari et al 2005;van Griensven et al 2007;Waters and Nelson 2007;Wierzbicki et al 2008). Stavudine is known as the antiretroviral drug with the strongest effects on mitochondrial activity, insulin resistance, and adipocyte growth, which are closely associated with the mechanisms of HIVassociated lipoatrophy (Waters and Nelson 2007;Mallewa et al 2008;Wierzbicki et al 2008). Stopping d4T treatment or switching to another non-thymidine analogue nucleoside reverse transcriptase inhibitors such as abacavir or tenofovir resulted in a significant gain of peripheral fat mass (Sutinen 2005;Wierzbicki et al 2008).…”

“…We excluded patients who were transferred from other clinics after HAART initiation or did not regularly visit every 3-6 months before enrollment. Also, patients who were currently taking peroxisome proliferator-activated receptor-gamma agonists, statins, metformin or growth hormone were excluded because these medications may affect changes of body fat (Mallewa et al 2008). We also screened and ruled out other current medical conditions that can produce muscle or fat wasting and mimic lipoatrophy, such as HIV/AIDS-associated wasting syndrome (Polsky et al 2004) according to the definition of the Centers for Disease Control and Prevention (CDC) published in 1987 (Centers for Disease Control and Prevention 1987), any opportunistic infection or malignancy undergoing current treatment, or underlying conditions of chronic liver or renal disease according to the International Classification of Disease, 10th Revision (World Health Organization 2006).…”

Oral sensorimotor system in AIDS patients with facial lipodystrophy

“…There are several references on such limitations involving the different strategies available to combat this syndrome and therefore there is a need to explore alternative options for action [44].…”

Impact of the Somatotrope Growth Hormone (GH)/Insulin-Like Growth Factor 1 (IGF-1) Axis Upon Thymus Function: Pharmacological Implications in Regeneration of Immune Functions

“…However, this therapy causes adverse events, which include metabolic changes termed lipodystrophy. Several mechanisms are underlying lipodystrophy and HIV itself may have a role in its aetiology [126]. Lipodistrophy, which occurs in 83% of HIV-infected patients with HAART, is associated with alterations in GH dynamics similar to what is observed in severe AGHD [127].…”