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Clinical Crossroads | Clinician's Corner

A 39-Year-Old Man With HIV-Associated Lipodystrophy

Jon Fuller, MD, Discussant
JAMA. 2008;300(9):1056-1066. doi:10.1001/jama.300.5.jrr80007.
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Human immunodeficiency virus (HIV)–associated lipodystrophy refers to fat accumulation, also known as lipohypertrophy, and fat wasting, also known as lipoatrophy. Both conditions can be very disturbing to patients and have been associated with metabolic disturbances such as insulin resistance and hyperlipidemias. The prevalence of HIV-associated lipodystrophy ranges from 6% to 69% in the medical literature. Although no clear associations have been made between specific drugs and HIV lipohypertrophy, stavudine and zidovudine have been implicated in the development of HIV lipoatrophy. The case of Mr B, a 39-year-old man with HIV-associated lipodystrophy whose facial changes are a cause of significant distress, highlights the need for clinicians to be attuned to the psychological impact that lipodystrophy can have on patients, especially because it may serve as a disincentive to adherence to antiretroviral drug regimens, resulting in an increased risk of developing viral resistance.

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Figures

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Figure 1. Human Immunodeficiency Virus–Associated Central Adiposity
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Photographs are of patients other than the case patient discussed herein.

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Figure 2. Human Immunodeficiency Virus–Associated Pseudovenomegaly
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Photograph is of a patient other than the case patient discussed herein.

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Lipodystrophy: A Disease of Diseases
Posted on August 8, 2008
Daniel M Riche, Pharm.D.
University of Mississippi Schools of Pharmacy and Medicine
Conflict of Interest: None Declared
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.
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