Large Particle Hyaluronic Acid for the Treatment of Facial Lipoatrophy in HIV-positive Patients: 3-year Follow-up Study

L Skeie; H Bugge; A Negaard; BM Bergersen


HIV Medicine. 2010;11(3):170-177. 

In This Article

Abstract and Introduction


Objectives Facial lipoatrophy can be a stigmatizing side effect of antiretroviral (AVR) treatment for HIV-infected patients. We sought to evaluate the long-term efficacy and safety of a new formulation of hyaluronic acid that can be injected in larger amounts and into deeper skin layers during 3 years of follow-up.
Methods Twenty patients received injections of Restylane SubQ™. Refill treatment was offered at 12 and 24 months. Treatment effects were evaluated using ultrasound, the Global Aesthetic Improvement Scale, visual analogue scale (VAS) and the Rosenberg self-esteem scale.
Results Seventeen patients remained at 36 months. Mean (± standard deviation) total cutaneous thickness increased from 6 ± 1 mm at baseline to 12 ± 1 mm (P<0.001) at 36 months. Response rate (total cutaneous thickness >10 mm) was 70%. Fifteen patients classified their facial appearance as very much or moderately improved. VAS increased from 39 ± 25 to 70 ± 20 (P<0.05) and higher self-esteem scores were reported. Local swelling and tenderness after treatment was common. Persistent papules found in several patients after treatment were removed effectively with hyaluronidase injections. Three patients, treated only at baseline, still had higher total cutaneous thickness scores at 36 months.
Conclusions Our results indicate that a large particle hyaluronic acid formulation is a durable and well-tolerated dermal filler for treating HIV-positive patients with facial lipoatrophy.


Lipoatrophy is a particularly distressing aspect of lipodystrophy evident in HIV-positive patients on antiretroviral therapy (ART). Facial lipoatrophy can severely affect patients' quality of life and may contribute to reduced antiretroviral (AVR) adherence.[1] Furthermore, the stigmatization affected patients may encounter as a result of facial lipoatrophy can be detrimental for self-esteem.[2] Treatment strategies include switching AVR regimens, prescription of medication, insertion of surgical implants and injection of dermal fillers.

While there is evidence that the use of new nonthymidine nucleoside reverse transcriptase inhibitors can prevent the development of lipoatrophy, switching medications, after lipoatrophy has progressed, offers only limited benefit.[3,4] A follow-up study of the Oslo HIV Cohort Study 2000 found that facial atrophy was less reversible than fat atrophy of the extremities.[5] Medications such as pioglitazone,[6] uridine[7] and pravastatin[8] have been shown to have some effect on limb lipoatrophy in HIV-infected patients; however, the mechanisms by which they work and their potential side effects are not well documented.

In the absence of a therapeutic intervention to reverse lipoatrophy, injection of soft-tissue fillers appears to be the simplest way to correct facial lipoatrophy. Many soft-tissue fillers, both biodegradable and permanent, have been studied in HIV facial lipoatrophy, however, long-term clinical safety and efficacy data are lacking. Biodegradable fillers have a good safety profile, but treatment with such fillers has to be repeated over time. Permanent fillers have a durable effect and the benefit of lower treatment costs, however, they may be difficult to remove if complications occur.[9]

Biodegradable fillers include hyaluronic acid, polylactic acid, collagen and calcium hydroxyapatite. Injectable silicone, polymethylmethacrylate microspheres and polyalkylimide gel are examples of permanent fillers. Injected autologous fat can be both non-permanent and permanent. In the treatment of HIV-associated lipoatrophy, few data are available beyond a 12-month follow-up period regarding the efficacy, safety and durability of both biodegradable and permanent fillers. Despite many studies documenting the use of polylactic acid to correct facial lipoatrophy in HIV-positive adults, only one study has published results from 3 years of follow-up.[10]

Injectable hyaluronic acid derivatives are widely used as biodegradable dermal fillers for soft-tissue augmentation in the general population today, and have replaced collagen as the standard injection material.[11] Hyaluronic acid products have been demonstrated to have a good safety profile, and few complications have been reported after the product was improved.[12] The hyaluronic acid product Restylane (Q-Med AB, Uppsala, Sweden) is produced from a hyaluronic acid preparation obtained by bacterial fermentation. The use of a non-animal source is thought to reduce the likelihood of antigenic contamination and subsequent hypersensitivity reactions. Natural hyaluronic acid found in the body is highly susceptible to enzymatic degradation and is rapidly reabsorbed in situ. As a result of this, hyaluronic acid derivatives are stabilized in order to improve their resistance to enzymatic degradation and prolong their cosmetic effect.[13] After treatment, hyaluronic acid chains are slowly released from the injected gel and biodegraded by the same mechanisms as those that degrade the body's own hyaluronic acid.

Restylane received approval by the Food and Drug Administration (FDA) in 2003.[12] The new Restylane product Restylane SubQ™ (Q-Med AB) was introduced in September 2004. The main difference between Restylane SubQ and other Restylane products is the size of the gel particles and the intended level of injection. Restylane SubQ has fewer gel particles (1000 gel particles/mL) and thus larger droplets than other Restylane products, and is therefore more viscous. As a result of this, the gel can be injected in larger amounts and into deeper skin layers,[13] an advantage given that HIV facial lipoatrophy typically involves larger atrophic surface areas than seen in the general population.

The use of a more viscous type of hyaluronic acid for the treatment of HIV-associated lipoatrophy has only been described previously in two studies, both with a follow-up period of 12 months.[14,15] The aim of our study was to evaluate the efficacy, safety and durability of a large particle hyaluronic acid in the correction of facial lipoatrophy in HIV-infected patients over a 3-year period. Twelve-month treatment results from this study have been reported earlier.[14] In the present study, we report longer-term efficacy, safety and durability data.


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