J. B. Sterling, MD, C. W. Hanke, MD, MPH, FACP
Laser and Skin Surgery Center of Indiana, Carmel, IN, USA
ABSTRACT
Poly-L-lactic acid is a filler recently approved by the US FDA for the correction of facial lipoatrophy in patients infected with the human immunodeficiency virus (HIV). Currently, poly-L-lactic acid, sold under the brand name Sculptra™ (Dermik), is the only product approved by the FDA specifically for this indication. The market for poly-L-lactic acid will likely be larger than the HIV-infected population, as physicians use poly-L-lactic acid off-label to correct lipoatrophy associated with the normal aging process in non-HIV-infected patients. The benefits of poly-L-lactic acid are limited by the fact that multiple treatments are necessary to achieve the desired correction; its results are temporary and its cost is high.
Key Words:
facial lipoatrophy, human immunodeficiency virus, HIV, poly-L-lactic acid
Poly-L-lactic acid (PLA) has been used safely in a variety of orthopedic and maxillofacial applications since the mid 1990s.1,2 In 1999, PLA was approved in Europe for the correction of scars and wrinkles. Recently the US FDA approved PLA for correction of HIV-associated facial lipoatrophy. Patients with this condition are injected every 2-6 weeks with PLA until the desired correction is achieved. Improvement is not permanent, but studies show continued skin thickening 2-3 years after injection. Adverse events have been minimal.
HIV Facial Lipoatrophy
Facial lipoatrophy can be a severe cosmetic problem for some HIV-infected patients and may be a sign of HIV lipodystrophy syndrome, which commonly occurs in HIV-infected patients who are treated with a combination of antiretroviral medications, especially protease inhibitors and nucleoside reverse transcriptase inhibitors. In these patients, fat redistributes away from the face and limbs, towards the central trunk, breasts, and dorsocervical fat pad. Dyslipidemia, insulin resistance, and osteoporosis may also be associated with the syndrome.
Facial lipoatrophy is characterized by sunken cheeks, bitemporal wasting, and deep nasolabial folds. Patients develop a hollow appearing face. This facial appearance is easily recognizable and can serve as a social stigma for HIV patients causing psychological stress. Many patients with HIV-associated facial lipoatrophy are eager to correct their appearance.
Composition of Sculptra™
Sculptra™ contains particles of PLA, which is a synthetic polymer of the alpha-hydroxy-acid family. Particles are 40-63mm in size and have a molecular weight of 140,000 Daltons. PLA is suspended in sodium carboxymethylcellulose and mannitol. PLA presumably creates a tissue response over the course of weeks to months characterized by a foreign body reaction and production of new collagen.3 The PLA is eventually metabolized to lactic acid monomers that are then metabolized to carbon dioxide or incorporated into glucose.
Sculptra™ is supplied as a freeze-dried product that must be reconstituted with sterile water 24 hours before injection.
Injection Techniqu
The patient’s cheeks are prepped with alcohol and marked with a sterile marking pen. The area to be treated is then anesthetized using multiple sticks of 1% lidocaine with 1:100,000 epinephrine preferably with a 30-gauge needle. One method entails injecting up to 10cc of local anesthesia after marking areas of lipoatrophy; this approach presupposes that Sculptra™ is useful for diffusely adding volume to broad areas of atrophy rather than precisely treating individual rhytides. Alternatively, some practitioners believe anesthesia should be used sparingly to avoid anatomic distortion; topical anesthesia or a regional block may, in this method, be used to augment small quantities of injected local anesthesia. In the Chelsea and Westminster study,4 the reconstitution of Sculptra™ was with 2ml sterile water for injection and 1ml 2% lidocaine.
Usually, one vial of Sculptra™ is necessary for each cheek. The package insert5 recommends reconstituting each vial with 3-5ml sterile water; however, it is the authors’ experience that a 5ml dilution decreases the risk of palpable nodule formation. Likewise, the package insert recommends reconstituting at least 2 hours before injection; however, 24 hours may lead to more complete dispersal of particles.
Injection is usually with a 1/2 inch 26-gauge needle, but some injectors prefer using other, longer needles, such as the 11/4 inch 25-gauge needle or the 11/2 inch 26-gauge needle. Longer needles may permit treatment with fewer punctures. Needles have a tendency to clog, so multiple needles must be available. Approximately 6 puncture sites are needed for each cheek. Through each puncture site, the suspension is injected in an even fan-like pattern (also referred to as a criss-cross or cross-hatch pattern), with multiple tunnels created at 0.5-1.0 cm intervals in the subcutaneous plane just below the dermis. Semantics can be confusing in this realm, as Dermik recommends serial punctures in the cheeks using threading or tunneling technique at 0.5-1.0 cm intervals.
After finishing the injection, the patient’s cheeks are then massaged for 5 minutes to ensure even dispersal of the product. No dressing is needed and the patient is instructed to apply ice packs to the treated areas for 15 minutes out of every hour while awake over the next 24 hours to avoid bruising. Immediately after injection, the patient’s cheeks appear fuller, which is a result of the mechanical effect of the large volume of anesthesia and fluid injected into the skin. Over the next 48 hours the correction disappears and the patient’s appearance returns to baseline. The manufacturer’s studies show that the skin will gradually thicken. Patients frequently need multiple treatments to achieve the desired correction. Treatments can be spaced at 2-6 week intervals.
The same injection technique can be used to treat facial lipoatrophy associated with the normal aging process in patients not infected with HIV.
Clinical Data
The clinical efficacy of PLA as a facial filler has been described in two large published clinical studies.4,5 Similar data, not yet published, were presented to the US FDA when Sculptra™ received approval in August 2004.
Moyle, et al.,4 in an open-label, randomized, and blinded 24-week study involving 30 HIV patients who were injected with PLA, demonstrated visible improvement and increased skin thickness. Patients who received injections at weeks -0, -2, and -4 maintained a mean increase in dermal thickness of 4-5mm at weeks 12 and 24 as measured by ultrasound. Reported adverse events were limited to bruising and superficial cellulitis not requiring antibiotics.
Valantin, et al.,6 in an open-label, single-arm study of 50 patients with HIV associated facial lipoatrophy reported a mean improvement in skin thickness of 6.8mm at 96 weeks as measured by ultrasound. Patients in this study received PLA at week-0, -2, -4, -6 and possibly another injection at week-8 depending on response. Adverse events were limited to bruising and, in 22 patients, palpable subcutaneous micronodules.
Woerle, et al.,7 reviewed their 5-year experience using PLA in 300 patients. Adverse events included bruising, erythema, and palpable subcutaneous nodules. The occurrence of subcutaneous nodules declined to less than 1% when they diluted PLA with a total of 3ml of sterile water and 2ml of 1% lidocaine (for a total dilution of 5ml of fluid). They also began to inject the material into the uppermost portion of the subcutaneous fat rather than the lower dermis.
Cost
Two vials of Sculptra™, typically necessary at each visit to treat both cheeks, cost approximately $980US, which does not include the physician’s fee. Patients typically need multiple treatments and, therefore, multiple vials are needed to achieve the desired correction. The results are not permanent and patients will need future treatments to maintain correction.
Alternatives
The two main alternatives to PLA for the treatment of HIV-associated lipoatrophy are silicone oil and autologous fat transfer.
Silicone oil is manufactured by Alcon Laboratories under the brand name Silikon™ 1000. It is a permanent filler that is US FDA approved for intraocular injection to treat retinal detachment. It has been used off-label to correct rhytides and soft tissue defects. A recent report by Jones, et al.8 demonstrated the efficacy and safety of Silikon™ 1000 in the HIV population.
Autologous fat transfer is another alternative to PLA for the treatment of HIV-associated lipoatrophy. This procedure involves harvesting fat from the abdomen or thighs for reinjection into the cheeks. A major disadvantage of autologous fat transfer is unpredictable fat graft survival. Additionally, in some cases, patients with lipoatrophy in the HIV setting may not have much fat to transfer or may have morphologically and histologically abnormal fat that may be less successfully transplanted.
Conclusion
PLA is a costly but promising treatment option for the correction of HIV-associated lipoatrophy. It has medium-term persistence, and may last up to several years at cosmetically effective levels. Clinicians will likely use PLA off-label to correct age-associated lipoatrophy in the non-HIV-infected patient population. Further clinical experience will be necessary to determine the long-term effectiveness of this product.
References
- Moe KS, Weisman RA. Resorbable fixation in facial plastic and head and neck reconstructive surgery: an initial report on polylactic acid implants. Laryngoscope 111(10):1697-701 (2001 Oct).
- Suuronen R, Haers PE, Lindqvist C, Saller HF. Update on bioresorbable plates in maxillofacial surgery. Facial Plast Surg 15(1):61-72 (1999).
- Gogolewski S, Jovanovic M, Perren SM, Dillon JG, Hughes MK. Tissue response and in vivo degradation of selected polyhydroxyacids: polylactides (PLA), poly(3-hydroxybutyrate) (PHB), and poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHB/VA). J Biomed Mater Res 27(9):1135-48 (1993 Sep).
- Moyle GJ, Lysakova L, Brown S, et al. A randomized open-label study of immediate versus delayed polylactic acid injections for the cosmetic management of facial lipoatrophy in persons with HIV infection. HIV Med 5(2):82-7 (2004 Mar).
- Package Insert. Sculptra (injectable poly-L-lactic acid). Berwyn, PA: Dermik Laboratories, 2004.
- Valantin MA, Aubron-Olivier C, Ghosn J, et al. Polylactic acid implants (New-Fill) to correct facial lipoatrophy in HIV-infected patients: results of the open-label study VEGA. AIDS 17(17):2471-7 (2003 Nov 21).
- Woerle B, Hanke CW, Sattler G. Poly-L-lactic acid: a temporary filler for soft tissue augmentation.
J Drugs Dermatol 3(4):385-9 (2004 Jul-Aug). - Jones DH, Carruthers A, Orentreich D, et al. Highly purified 1000-cSt Silicone oil for treatment of human immunodeficiency virus-associated facial lipoatrophy: an open pilot trial. Dermatol Surg 30(10):1279-86 (2004 Oct).
