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Clinical Crossroads: Jon Fuller A 39-Year-Old Man With HIV-Associated Lipodystrophy JAMA 2008; 300: 1056-1066 [Abstract] [Full text] [PDF]

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Lipodystrophy: A Disease of Diseases

Daniel M Riche   (4 September 2008)

Lipodystrophy: A Disease of Diseases 4 September 2008
Daniel M Riche, Pharm.D. University of Mississippi Schools of Pharmacy and Medicine Send response to journal: Re: Lipodystrophy: A Disease of Diseases driche{at}sop.umsmed.edu Daniel M Riche	HIV-associated lipodystrophy occurs in patients treated with antiretroviral medications (most commonly protease inhibitors [PI]). The components of lipodystrophy include abnormal central fat accumulation (lipohypertrophy) and localized loss of fat tissue (lipoatrophy). Dyslipidemia is also a long-term metabolic complication of both HIV disease and treatment. Typically, dyslipidemia presents as elevated triglycerides (TG) and low high-density lipoprotien (HDL), the suspected cause of increased myocardial infarction in patients receiving PI.[1] Management of these disorders is multifactorial and must be individualized. Additional concerns in HIV-associated lipodystrophy is detriment to the psyche. While the degree of self-image changes are variable, the one commonality among patients is that a clinician who simply listens improves the feeling of self-worth.[2] For Mr B, there are several immediate concerns. The alcohol use, combined with very elevated triglycerides (TG) and nRTI use (particularly lamivudine), places this patient at a high risk for pancreatitis. TG reduction is absolutely necessary. Considering the vegetarian diet, lifestyle emphasis should be on smoking cessation (increases HDL) and alcohol cessation (decreases TG and risk of pancreatitis). The dyslipidemic agent of choice is likely fenofibrate as it is reported to decrease TG [~55%] and increase HDL [~25%] with TG >500 mg/dL without significant drug interaction or additive adverse effect.[3] Additional, TG reduction may be needed and can result from a thiazolidinedione.[4] Though the patient has not developed a glucose abnormality, pioglitazone has significant evidence in the area of lipodystrophy.[5] Pioglitazone 30 mg/day improved limb fat atrophy in antiretroviral-treated HIV-1-infected patients with a favorable lipid profile. This effect, particularly to dyslipidemia, seems isolated to pioglitazone in the thiazolidinedione class.[6] Another concern is the use of a dual PI-based regimen. The dose of lopinavir/ritonovir (LPV/r) may be increased to 600mg lopinavir/150mg ritonavir twice daily in treatment-experienced patients when decreased susceptibility to lopinavir is suspected. Mr. B has a history of good response to LPV/r in 2004. There is no reason to suspect decreased susceptibility, thus the dose of LPV/r is higher than currently recommended in a patient concomitantly on fosamprenavir (FPV). The dose should be reduced to 400mg lopinavir/100mg ritonovir twice daily, decreasing the risk of hypertriglyceridemia, pancreatitis, and lipodystrophy [all adverse drug effects and precautions].[7] The question of 4-drug regimens also exists. A dual PI-based regimen was recently evaluated, using LPV/r and FPV.[8] The activity and safety of LPV/r + FPV to LPV/r or FPV + ritonovir was evaluated. There was no difference between dual versus single PI in the ITT analysis, but dual PI was improved in an evaluable population. The PI-based regimens that are considered "cleaner" in terms of metabolics are atazanavir and saquinivir with ritonovir boosting.[9] The final issue of lipoatrophy that can be considered is response to facial atrophy. Sculptra contains poly-l-lactic acid (PLLA), which is thought to elicit in vivo collagen production around the injected implant, producing new volume gradually over time, and with effects lasting up to 2 years.[10] The cost of PLLA would mean the patient's most likely chance to obtain this agent is via the company's patient assistance program, and should depend on the patient’s preference and self-image. Dr. Riche is on the Speakers Bureau for Pfizer. References: 1) Friis-Møller N, Sabin CA, Weber R,et al. Combination antiretroviral therapy and the risk of myocardial infarction. N Engl J Med. 2003;349:1993 -2003. 2) Reynolds NR, Neidig JL, Wu AW, Gifford AL, Holmes WC. Balancing disfigurement and fear of disease progression: Patient perceptions of HIV body fat redistribution. AIDS Care. 2006;18:663-73. 3) Tricor [package insert]. North Chicago, IL: Abbott Laboratories; November 2004. 4) Goldberg RB, Kendall DM, Deeg MA, et al. A comparison of lipid and glycemic effects of pioglitazone and rosiglitazone in patients with type 2 diabetes and dyslipidemia. Diabetes Care. 2005 Jul;28(7):1547-54. 5) Kaletra [package insert]. North Chicago, IL: Abbott Laboratories; November 2007. 6) Slama L, Lanoy E, Valantin MA, et al. Effect of pioglitazone on HIV-1- related lipodystrophy: a randomized double-blind placebo-controlled trial (ANRS 113). Antivir Ther. 2008;13(1):67-76. 7) Feldt T, Oette M, Kroidl A, et al. Evaluation of safety and efficacy of rosiglitazone in the treatment of HIV-associated lipodystrophy syndrome. Infection. 2006;34(2):55-61. 8) Collier AC, Tierney C, Downey GF, et al. Randomized study of dual versus single ritonavir-enhanced protease inhibitors for protease inhibitor-experienced patients with HIV. HIV Clin Trials. 2008;9:91-102. 9) Lundgren JD, Battegay M, Behrens G, et al. European AIDS Clinical Society (EACS) guidelines on the prevention and management of metabolic diseases in HIV. HIV Med 2008;9(2):72-81. 10) Lowe NJ. Optimizing poly-L-lactic acid use. J Cosmet Laser Ther. 2008;10:43-6.