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Facing Facts About Lipoatrophy

People who are unable to hide their aging appearance can sometimes experience eroded self-image and a lack of self-esteem. In some cases, clinical depression and social isolation occur, and among HIV patients, lipoatrophy can lead to poor compliance with therapy.[1-3]

As Professor Albert Kligman eloquently stated more than 15 years ago, "An aged, degraded skin is uncomfortable to live in. It is also unattractive and leads to aversive reactions by others.[3] The unhandsome aged have trouble maintaining self-esteem when they recollect the smooth, unmarked, turgid skin that was the clothing of their youth."

Left untreated, elderly individuals, who may already have fewer social contacts over time, can be confronted with a further lessening of contact with potential providers of support, including healthcare providers. Enhancing appearance provides a psychological boost that may lead to positive thoughts and actions.[3] Most importantly, in HIV, treatment in the most severely affected patients has been shown to reduce the physical consequences of facial fat loss.[4] The purpose of this series of articles is to review the changes in fat distribution that lead to facial lipoatrophy. Clinical strategies to assess lipoatrophy and treatment options using temporary and semipermanent fillers are also reviewed.

Morphologic Changes Related to Fat Distribution
The morphologic changes in the face at each stage of life result from changes in fat distribution. Fat atrophy occurs in the periorbital, forehead, buccal, temporal, and perioral areas, whereas fat hypertrophy becomes evident under the chin and in the jowl, lateral nasolabial fold, lateral labiomental crease, and lateral malar areas.[5]

Many conditions, in addition to the normal aging process, are associated with the development of wrinkles and facial lipoatrophy (Table 1). Reported risk factors in patients with HIV include higher nadir HIV load and the use of non–thymidine-sparing nucleoside reverse transcriptase inhibitors (NRTIs). Highly active antiretroviral therapy (HAART) also appears to be a contributing factor, with longer treatment duration associated with increased onset and severity of lipoatrophy.[6,7]

The diverse predisposing factors for facial lipoatrophy suggest a complex, multifactorial pathogenesis, and there is evidence that impaired adipocyte differentiation, adipokine regulation, unopposed production of proinflammatory cytokines, dysregulation of 11-beta-hydroxysteroid dehydrogenase, and mitochondrial toxicity may play a role.[6]

Table 1. Conditions That Result in Wrinkles and Facial Lipoatrophy

• Normal aging
• HIV, especially with HAART therapy
• Cachexia; extreme endurance exercise
• Diabetes
• Hereditary syndromes (familial partial lipodystrophy)
• Autoimmune disorders (linear scleroderma, lupus panniculitis)

Therapeutic interventions

Once lipoatrophy occurs, the goal of treatment is the same -- reestablish the arcs and convexities that characterize the young face. There are no proven therapies to reverse or prevent peripheral lipoatrophy. Aside from cosmetic surgery, an array of temporary, semipermanent, and permanent injectable fillers are available to correct altered fat distribution. Other potential options in patients with HIV include switching antiretroviral drugs and administering thiazolidinediones. The use of antioxidants/co-factors has also been suggested.[8]

Cosmetic surgery: Despite the increasing demand and popularity of facial rejuvenation procedures, there has been little real change of traditional surgical techniques during the past few decades.[9] Surgical intervention as a treatment option for facial lipoatrophy produces less than optimal results, because it fails to address the primary issue of volume loss, and the unwanted results of traditional procedures become easy to recognize over time. For example, the unopposed tension of lateral vector face-lifts allows the cheek tissues to descend eventually over the tightened jawline, creating a "lateral sweep'" or pulled appearance of the face.[9]

Injectable fillers: Five temporary injectable fillers have been approved by the US Food and Drug Administration (FDA) and are available for use. The products in Table 2 and Table 3 reflect the categories established by the American Society of Plastic Surgeons.[10] The response to temporary fillers lasts less than 1 year following treatment. In addition, autologous fat transplantation is achieved by taking fat from the butt, hips, inner thighs, or abdomen and (after cleaning and filtering) injecting it into another part of the body, such as the face.

Semipermanent fillers are designed to prevent rapid breakdown by the body. Two are approved for use in the United States -- poly-L-lactic acid (Sculptra) and calcium hydroxylapatite (Radiesse). The duration of effect lasts up to 2 years following treatment with poly-L-lactic acid, which is the only Food and Drug Administration (FDA)-approved facial filler for the reconstructive management of HIV-associated facial lipoatrophy.

The FDA has not approved the use of permanent fillers for dermal augmentation. Silicone, polymethyl methacrylate (PMMA; Artecoll, ArteFill), and polyalkylamide (Bio-Alcamid) are in various stages of clinical development for use in the United States. One drawback to their use in facial lipoatrophy is that as lipoatrophy progresses, a gaunt appearance may become more pronounced. These products cannot be removed.[11]

Antiretroviral switch studies: The results of several studies reveal that stopping or switching protease inhibitors (PIs) has minimal or no effect on body composition. Among NRTIs, especially the thymidine NRTIs, stavudine-treated patients reportedly experience greater subcutaneous fat loss and visceral fat gain than antiretroviral-naive or zidovudine-treated HIV-infected patients.[12]

Thiazolidinediones: This class of insulin-sensitizing agents includes rosiglitazone (Avandia) and pioglitazone (Actos), which are approved for use in patients with type 2 diabetes. A small study reported a benefit of rosiglitazone on limb fat,[13] but a larger, randomized, placebo-controlled, 48-week study failed to show significant differences in limb fat in subjects with HIV lipodystrophy treated with rosiglitazone compared with placebo.[14]

Antioxidants/Co-factors: Among the agents included in this group are vitamins B1 (thiamine), B2 (riboflavin), C, and E, as well as carnitine, acetyl carnitine, and co-enzyme Q. No prospective studies are currently available on the efficacy of these agents.[8]

Table 2. Temporary Injectable Fillers

Compound Brand name*
Collagen (bovine) Zyderm; Zyplast
Collagen (human) CosmoDerm; CosmoPlast
Human cadaveric dermis Cymetra; Dermalogen
Human cadaveric fascia Fascian
Hyaluronic acid Restylane; Hylaform; Hylaform Plus; Captique
* Check official product information for availability and approved uses in the United States.


Table 3. Semipermanent Injectable Fillers

Compound Brand name*
Calcium hydroxylapatite Radiance; Radiesse
Poly-L-lactic acid Sculptra
* Check official product information for availability and approved uses in the United States.

Facing Facts About Lipoatrophy

Documenting the Degree of Facial Lipoatrophy
The treatment plan begins with an assessment and documentation of the degree of facial lipoatrophy. A 3-point scale (mild, moderate, or severe) is commonly used by clinicians to categorize the extent of lipoatrophy. However, by broadening the lower levels -- the mild to moderate levels -- it is possible to refine this assessment, particularly in patients where the etiology of facial lipoatrophy is associated with aging.

The figure below compares the physical appearance of lipoatrophy using the 4-point scale. A small, localized area of fat loss characterizes grade 1. In grade 2, more than 1 area is affected (generally including the jowl and oral commissure). A larger area with distinct shadowing characterizes grade 3 lipoatrophy; the patient with severe fat depletion in all facial regions, with protruding musculature and bones, is assigned grade 4.[15] Completing this assessment prior to treatment provides a baseline against which the response to current treatments can be compared. In addition, it guides physicians and patients on any future therapeutic decisions and procedures.

Figure 1. A youthful face (top left) followed by 4 grades of facial lipoatrophy (1 [least severe] to 4 [most severe]). Reprinted with permission from Cosmetic Dermatology. 2006;19(suppl 1):3-5. 2006, © Quadrant HealthCom Inc.

Facing Facts About Lipoatrophy

Treatment of facial lipoatrophy is justified to overcome the physical and social consequences of facial fat loss that occur as a natural part of aging or as a consequence of certain diseases and drug therapy. During the past quarter century, many new treatments have been developed and approved by the FDA. Other compounds and modifications of previously approved compounds are being developed and are likely to become available during the next few years.

FDA oversight and approval are important because the availability of thoroughly tested and approved products offers reassurance that a pure formulation can be obtained from a reliable source. For best results, physicians must be trained and skilled in the injection techniques and be prepared to use a combination of techniques to achieve the best results for their patients.


The Aging Face: Initial Assessment and Consultation

In my practice, I see many men and women who are distressed by the normal effects of aging on their appearance. They don't mind getting older; they just don't want to look "old." They want to look as young as they feel. Yet, their facial expression is slowly changing, and not for the better. One woman told me, "My face is falling, and I can't get it to go back up again!" Funny? Yes, but not to her.

Real or perceived physical unattractiveness can result in insecurity, anxiety, and fear. It can alter intimate relationships and social interactions. It can even extract a "plainness penalty" in the labor market. For example, one study of earnings differentials among approximately 600 men and women who were rated on attractiveness by interviewers revealed that plain people generally earn 5% to 10% less than average-looking people, and average-looking people earn slightly less than good-looking people.[1]

When viewed from this perspective, facial rejuvenation can be an important aspect of career development. As our population ages and older people remain in the workforce longer, natural changes to facial features will become more common. Addressing these changes can turn back the biologic clock. For example, Figure 1 shows the response to poly-L-lactic (Sculptra) acid in a 65-year-old chief executive officer who wanted to look younger because he believed it would be beneficial to his business. In order to meet this objective, a volumetric approach to his mid and lower facial areas reestablished gentle contours by filling in the preauricular area, the malar fat pad, the nasolabial folds, and the buccal area.

Figure 1. Areas of treatment with poly-L-lactic acid are highlighted in a 65-year-old executive at baseline (A) and after 2 treatment sessions (B). Reprinted with permission from Cosmetic Dermatology. 2006;19(suppl 1):6-8. © 2006, Quadrant HealthCom Inc.

The Aging Face: Initial Assessment and Consultation

Signs of Facial Aging
The young face is characterized by an even distribution of ample fat and collagen that produces a "gently rolling plain" with more points of highlight than shadow. These points are complemented by a series of convexities and arcs. Aging produces dynamic and multifactorial facial changes (Table 1). Thus, the examination begins with looking for changes in appearance in the upper, mid, and lower face. Skin sags as muscle tone decreases, particularly in the chin and neck. The skin appears thinner and more translucent due to fat loss, the loss of elasticity and collagen, and it becomes drier and more wrinkled. Sun-damaged skin is more susceptible to these changes and appears to age faster than skin that has been protected by sun block and shade from a hat.


Table 1. Effects of Facial Aging

• Thinning of dermis
• Greater visibility of bony landmarks
• Hollowing of the cheek in mouth area
• Descent of facial fat pads and deepening of nasolabial folds
• Thinning of lips
• Descent of the corners of the mouth
• Ptosis of the nasal tip
• Decreased support of the lower face

Figure 2 illustrates the natural facial changes that occur with aging. In the upper face, these primarily consist of forehead, glabellar, and lateral canthal rhytids, as well as brow ptosis. Signs of aging in the periorbital areas may be most prominent (illustrations 1 and 2).

Cheek rhytids appear in the mid face. Contour deficits become prominent, and fat loss is evident in the preauricular area. The malar fat pad descends, nasolabial folds become more prominent, and buccal fat recedes (illustrations 2 and 3).

Over time, cobblestoning of the chin occurs in the lower face, and perioral fine lines, a diminished vermillion border, lip lengthening and a loss of lip volume, a down-turning mouth, and mentolabial lines (marionette lines) appear (illustrations 3 and 4).

Assessing the Aging Face
There are no widely accepted techniques for assessing facial lipoatrophy. Magnetic resonance imaging of the face has been used as a research tool to assess facial fat in non-HIV-infected patients. Skinfold measurement of the Bichat's area (area of fat beneath the cheeks) using calipers was described in one study of HIV-infected patients, but has yet to be validated.[2]

The goal of facial rejuvenation is to achieve a natural, youthful appearance. Assessment begins by determining the patient's subjective and objective perceptions. This is followed by a physical assessment of the face. Use of a grading system is important to establish a baseline that can be used to document improvement following treatment, and it can be referred to in the future. Finally, a treatment strategy is developed that will achieve realistic expectations using the most appropriate treatments (Table 2).

Table 2. Options for Facial Rejuvenation

Objective Treatment Options
Superficial rejuvenation
  • Topical antiaging cream
  • Superficial peels
  • Microdermabrasion
Dermal remodeling
  • Nonablative facial rejuvenation (lasers)
  • Radiofrequency devices  
Muscle relaxation
  • Botulinum toxin type A
Soft tissue augmentation
  • Filler agents
Deeper rejuvenation
  • Laser resurfacing
  • Medium peels
  • Deep peels
  • Plastic surgery
Advantages to Pharmacologic Treatment Options
It has been noted that despite the growing demand for and popularity of facial rejuvenation procedures, traditional techniques have not changed much during the past few decades.[3] The downsides of surgery are easy to recognize. For example, unopposed tension of lateral vector face-lifts allows cheek tissues to gradually descend over the tightened jawline, creating a "lateral sweep" or pulled appearance of the face. Conventional blepharoplasty causes the lower eyelid contour to become deeper, often forming a hollow appearance. Other unwanted physical changes have been reported as well.[3]

Fortunately, pharmacologic treatments offer a significant advantage over surgical facial rejuvenation techniques. Other topical therapies, such as retinoids, alpha-hydroxy acids, and others, are essential for overall improvement in complexion, tone, and texture. Chemical peels and microdermabrasion are great adjuncts.  Pharmacologic treatment options are generally well tolerated and produce excellent temporary results lasting from a few months (collagen injections) to as long as 2 years (treatment with poly-L-lactic acid). As with surgery, the skill of the injector is critical to achieving a satisfactory response.

Exploring Management Options for Facial Lipoatrophy: Focus on Semipermanent Fillers

How others view us is important from a social as well as an economic perspective.[1] Our face is the most important area of the body in terms of influencing and regulating interactions with others. It reflects our attitudes and intentions and is the primary area in the body associated with expressing emotions and individual identity.[2] Arguably, our face plays its most important role in influencing aesthetic judgments about us by others. People readily make judgments about attractiveness and personality traits on the basis of even limited exposure to a face.[2]

Although it is possible to offset the appearance of lipoatrophy with dermal fillers, botulinum toxin, as well as with face-lifts and liposculpture, more precise management of lipoatrophy is achieved by restoring the fat and soft tissue loss that is the underlying cause of these facial changes. In this article, the options for optimal facial rejuvenation for those with lipoatrophy are reviewed. The semipermanent fillers (poly-L-lactic acid [Sculptra] and calcium hydroxylapatite [Radiesse, previously Radiance FN]) are of particular interest because of their safety, relative ease of use, and durable response. Poly-L-lactic acid is approved by the FDA for the treatment of patients with facial lipoatrophy in the setting of HIV–generally the most severe cases of facial lipoatrophy. Autologous fat transfer, which does not require FDA approval, is also briefly discussed.

The 5 R's of Facial Aesthetics
The optimal interventions to correct the facial changes associated with aging can be selected from among the "5 R's" of facial aesthetics (Table 1). Restoration is best accomplished using soft tissue fillers (as described later) and should be distinguished from other interventions. For example, when relaxation is required, botulinum toxin is injected into specific muscles to relax and improve lines, wrinkles, and furrows associated with facial expression.

Resurfacing to treat wrinkles, skin discoloration, and age spots, as well as dull skin texture and mild acne scars, is achieved through the use of chemical peels, laser resurfacing, and dermabrasion. Redraping to treat redundant skin and soft tissue is achieved with face- and neck-lifts. These techniques remove sagging and redundant skin, particularly from the lower third of the face and under the chin. Redefining is accomplished through tumescent liposculpture to remove excess adipose, particularly in the jowls and submentum, to provide greater definition to the neck and jaw line.

Table 1. The 5 "R's" of Facial Aesthetics

Intervention Anatomical Defect Treatment Options
Relaxation Facial musculature
  • Botulinum toxin
Restoration Volume loss lipoatrophy
  • Soft tissue fillers
  • Fat
  • Implants
Resurfacing Surface changes
  • Chemical peels
  • Laser resurfacing
  • Dermabrasion
Redraping Redundant skin and soft tissue
  • Face-lift
  • Neck-lift
Redefining Jaw line and neck
  • Liposculpture


Exploring Management Options for Facial Lipoatrophy: Focus on Semipermanent Fillers

Restoration seeks to put back the volume lost in facial lipoatrophy. This volume loss is most noticeable due to atrophy of the buccal fat pads and dermal/subcutaneous layers.[3] Lipoatrophy exaggerates the appearance of wrinkles and leads to sunken cheeks and temples, skeletonization of the orbits, accentuated facial folds with shadowing, and protruding facial musculature and bony landmarks, which give the face an angular appearance. Restoration of facial contours can be achieved using a variety of products, which the American Society of Plastic Surgeons categorizes as temporary, semipermanent, and permanent fillers.
Temporary Fillers
The effects of temporary dermal fillers generally last 3 to 9 months and as long as 12 months, depending on the product used (Figure 1).[4] In addition to commercially available products, autologous dermis can be utilized. All of the products are injected into the dermis to address fine to course rhytids, as well as furrows. Dermal fillers are less well suited for contouring the face and reestablishing facial arcs and fullness. Because of the large volumes usually required to successfully treat HIV-associated lipoatrophy, collagen is generally not used in these cases.

Allergy testing is required before using bovine collagen to mitigate the 3% to 5% risk of hypersensitivity. Intradermal testing before using human collagen and hyaluronic acid products is not required (Table 2).[5-13] Cutaneous necrosis occurs when a vessel is canalized and injected inadvertently. This can pose a risk with any of these or other products, but it is rare. Blindness has been reported when an intra-arterial injection occurs in the glabellar region and occludes the retinal artery due to retrograde flow. Again, this is exceedingly rare but can occur with any cutaneous filler used in this region.

Products derived from human cadavers at the time of death include the dermis (Cymetra for correction of soft tissue defects) or muscle fascia (Fascian used for soft tissue augmentation, as well as acne scarring and other scars), which are harvested and then sterilized, tested, and processed. Allergy testing is not necessary, and the response lasts from 3 to 9 months. Administration requires a large-gauge needle and frequent touch-ups. These products are not FDA approved for use in HIV-associated lipoatrophy. In addition, Isolagen, which uses naturally produced autologous fibroblast cells, is in clinical development in the United States.

Hyaluronic acid, which is available under several brand names, is a natural component of connective tissues, including the skin. It is manufactured using recombinant technology, and because it is a naturally occurring substance in humans, allergic reactions are rare, and skin testing is not required. The response to hyaluronic acid lasts 6 to 12 months. Postinjection recovery can be uncomfortable and accompanied by more redness, bruising, and swelling than the collagen products. Large volumes are required to correct significant facial lipoatrophy.

Table 2. Temporary Injectable Fillers[5-13]

Compound (Brand, Company) Clinical Use Adverse Reaction
Autologous fibroblast cells

(Isolagen, Isolagen, Inc.)
In clinical development in the United States to treat scar tissue, facial wrinkles, acne scars, and skin tissue burns.  
Collagen (bovine)

(Zyderm I, II, Inamed)

(Zyplast, Inamed)

  • Rhytids, fine and coarse
  • Atrophic scars
  • Lip augmentation
  • Folds, grooves
  • Allergic reaction (skin testing required)
  • Soft tissue swelling
  • Bruising
  • Skin necrosis (rare)
  • Blindness (remote)
Collagen (human)

(CosmoDermI, II, Inamed)

(CosmoPlast, Inamed)

  • Rhytids, fine and coarse
  • Atrophic scars
  • Lip augmentation
  • Folds, grooves
  • Soft tissue swelling
  • Bruising
  • Skin necrosis (rare)
  • Blindness (remote)
Human cadaveric dermis

(Cymetra, LifeCell Corp.)
  • Coarse rhytids
  • Lip augmentation
  • Folds and grooves
  • Soft tissue swelling
  • Bruising
Human cadaveric fascia

(Fascian, Fascia Biosystems)
  • Coarse rhytids
  • Lip augmentation
  • Folds and grooves
  • Soft tissue swelling
  • Bruising
Hyaluronic acid

(Captique, Inamed)

(Hylaform, Inamed)

(Hylaform Plus, Inamed)

(Restylane, Medicis Aesthetics Inc.)
  • Coarse rhytids
  • Atrophic scars
  • Lip augmentation
  • Folds and grooves
  • Soft tissue swelling
  • Bruising
  • Postoperative discomfort (rare)
Semipermanent Fillers
Autologous fat transfer and 2 synthetic products (calcium hydroxylapatite [Radiesse] and poly-L-lactic acid [Sculptra]) are categorized as semipermanent fillers, reflecting their comparatively durable response compared with temporary fillers (Table 3).[14,15]

Poly-L-lactic acid is the only commercial product that is FDA approved for the reconstructive management of HIV-associated lipoatrophy. It comes as a freeze-dried powder (2 vials per box). The author reconstitutes the product using 5 mL of sterile water for injection plus 1 mL of lidocaine. Usual treatment requires 6 mL per side of face per session. Volume restoration is real but gradual and incremental with subsequent treatments. Generally 3 to 6 sessions are needed, and the results last up to 2 years with repeated treatment.

In an open-label, single-arm trial of patients (N = 50) with HIV, 4 sets of injections were administered on day 0 and then every 2 weeks for 6 weeks for a total of 4 treatment sessions. Facial thickness confirmed by biopsy on day 0 ranged from 0.0 to 2.1 mm. Following treatment, 43% of patients achieved total cutaneous thickness greater than 10 mm. Skin biopsy at the control site increased dramatically.[16]

The most commonly observed adverse event associated with the use of poly-L-lactic acid is delayed occurrence of subcutaneous papules at the injection site, which are typically palpable, asymptomatic, and nonvisible. Recently, 3 case histories were reported of patients who developed granulomatous skin reactions 12 months or more after dermal injection with poly-L-lactic acid.[17]

As opposed to poly-L-lactic acid in which response to treatment is delayed and suspected due to increased collagen deposition, clinical response to calcium hydroxylapatite is directly related to injection volume. Clinical results last for 9 to 12 months and sometimes as long as 18 months. In one study of adults (N = 90), appearance, softness, and overall patient satisfaction at 6 months after treatment were rated good or excellent in 74%, 80%, and 88% of patients, respectively. Calcium hydroxylapatite is generally well tolerated. Precise technique is required with lip augmentation to reduce the risk of submucosal nodules. Even in experienced hands, approximately 10% of patients treated in the lips will develop nodules. Most often the nodules are not visible and resolve without intervention.[18]

Autologous fat transplantation is performed using manual low-pressure tumescent liposuction to harvest fat from fat-rich areas, such as the buttocks, hips, inner thighs, or abdomen, for transfer to fat-poor areas. The fat is purified and transferred to 1-mL syringes under sterile conditions for injection using a tiny blunt cannula. The response to treatment generally lasts 6 to 12 months but may endure for up to 2 years.

The advantages of this option are that it is a nonforeign material with a natural look and feel. Although it is possible to harvest a sufficient amount of fat for future treatments, the disadvantages include that it requires a surgical procedure, there is a risk of a longer recovery postoperatively, and finally, especially in the case of patients with HIV-associated facial lipoatrophy, there may be a paucity of central body fat to draw from.

Table 3. Synthetic Semipermanent Injectable Fillers[14,15]

Compound (Brand) Onset Duration Adverse Reactions
Calcium hydroxylapatite

(Radiesse, Bioform)
Immediate 15-18 months
  • Bruising
  • Erythema
  • Nodule formation (esp. in lips)
  • Granulomas
  • If injected on bone (under periosteum), bone formation can occur
Poly-L-lactic acid

(Sculptra, Dermik Aesthetics)
Full effects in weeks to months Up to 24 months with repeat treatments
  • Bruising
  • Erythema
  • Nodule formation
  • Granulomas


Permanent Fillers
Silicone (Silikon 2000) and polymethyl methacrylate (PMMA; ArteFill) are synthetic products that are not readily metabolized and removed by the body.[19,20] Silikon 2000 is being studied for the treatment of HIV facial lipoatrophy. It is used off-label for the treatment of atrophic scars, as well as lip and nasolabial fold augmentation.[19] Artifill is in the final stages of FDA approval as a permanent injectable implant for the treatment of soft tissue defects of the face.[20] The value of a permanent product is obvious. However, the risk of permanence is that it cannot be modified once placed.
Many treatment options are available for rejuvenation in the setting of facial lipoatrophy. With careful assessment, the appropriate intervention can be identified and used to correct the inevitable effects of aging on appearance, as well as the facial changes that accompany HIV. For restoration of facial lipoatrophy, temporary dermal fillers are minimally helpful, because they only address fine and coarse rhytids, folds, and grooves that occur secondarily.

The semipermanent fillers, such as poly-L-lactic acid, calcium hydroxylapatite, and fat, on the other hand, address facial lipoatrophy itself and are capable of recontouring and lifting the face to restore youthful arcs and convexities. Unlike fat transfer, administration of synthetic semipermanent fillers does not require a surgical procedure, and it is relatively easy to re-treat patients as aging and advancing lipoatrophy progress.

Permanent fillers and implants are enticing to patients as a "forever" corrective option. However, when treatment imperfections do occur, remedies can be problematic. The semipermanent fillers provide enough durability and flexibility to balance the risk-benefit conundrum.

It has been 2 years since poly-L-lactic acid (Sculptra) was approved in the United States for restoration and correction of the signs of facial fat loss (lipoatrophy) in people with HIV.[1] Outside the United States, poly-L-lactic acid (marketed as NewFill) was approved in the category of "wrinkle filler" in 1999 and for large-volume corrections of the signs of lipoatrophy in early 2004 by the French Notified Body G-Med (Department of Evaluation of Medical Devices).[2]

Thus, in the past 6 years, poly-L-lactic acid has been used to treat patients in more than 30 countries for a variety of facial volume and contour deficiencies, including signs of aging such as wrinkles, folds, and sunken cheeks. In addition, this remarkable agent is now being evaluated for a broad range of applications, from maxillary stability following surgery to the development of biodegradable thermosensitive nanoparticles as a potential anticancer drug carrier.[3,4] This article focuses on the supporting clinical trial data and current recommendations for the optimal use of poly-L-lactic acid as a facial contouring agent.

Composition and Mechanism of Action of Poly-L-Lactic Acid
The FDA lists poly-L-lactic acid as an injectable medical device. It is composed of an immunologically inert, synthetic biocompatible, biodegradable, absorbable polymer of the alpha-hydroxy-acid family, which is suspended in sodium carboxymethylcellulose and nonpyrogenic mannitol.

For a period of weeks to months, poly-L-lactic acid creates a tissue response characterized by a foreign-body reaction and new collagen production.[5] The response is not permanent, and poly-L-lactic acid is eventually metabolized into lactic acid monomers, which are in turn metabolized to carbon dioxide and water.

Poly-L-Lactic Acid in Clinical Trials
The results of 2 pivotal clinical trials supported the approval of poly-L-lactic acid in the United States. In the first trial of HIV-positive patients (N = 50) with severe facial lipoatrophy, poly-L-lactic acid was administered as 4 sets of injections at day 0 and every 2 weeks for 6 weeks. Median total cutaneous thickness (TCT) increased significantly (P < .001) from baseline (where median facial fat thickness was set at 0) to +5.1 mm at week 6, +6.4 mm at week 24, +7.2 mm at week 48, +7.2 mm at week 72, and +6.8 mm at week 96 (Figure 1).[6]

The temporal association between treatment and outcomes was evaluated in a 24-week study of HIV-positive individuals (N = 30) with facial lipoatrophy who were randomly assigned to immediate or delayed treatment with poly-L-lactic acid injections placed bilaterally into the deep dermis overlying the buccal fat pad.[7]

Patient visual analogue scores, photographic assessments, and anxiety and depression scores as measured by the Hospital Anxiety and Depression Scale improved with treatment in both groups. However, at week 12, immediate-treatment patients had significantly better visual analogue score (7 vs 1, P < .001) and lower anxiety scores (6 vs 9), which approached significance (P = .056), compared with delayed-treatment patients. The benefits of treatment persisted through week 24.

Mean increases in dermal thickness (4 to 5 mm) were noted at week 12 in the cheek and nasolabial regions in patients receiving immediate treatment, but not in the delayed-treatment group (Figure 2). Differences in dermal thickness were significant (P = .001) between groups at week 12, but not at week 24 of therapy.

Adverse Events
Bruising, erythema, and slight swelling occur frequently at the injection site and persist for a few days following treatment. The prevalence of subcutaneous papules ranges from less than 1% to 10% and appears to be related to the method of drug reconstitution.[8] Table 1 lists injection procedure-related adverse events observed in the 2 pivotal clinical trials of poly-L-lactic acid, with 2-year follow-up.

Table 1. Patients With Treatment-Related Adverse Events Observed in Clinical Studies of Poly-L-Lactic Acid, With 2-Year Follow-up

Adverse Event Valantin et al, 2003 Moyle et al, 2004† Average Duration(days)
Injection procedure-related
• Bruising 3 (6%) 11 (38%) 6
• Edema 2 (4%) 2 (7%) 3
• Discomfort 0 3 (10%) 3
• Hematoma 14 (28%) 0 17
• Inflammation 0 3 (10%) 3
• Erythema 0 3 (10%) 3
Device-related Average Onset (months)‡
• Injection site subcutaneous papule* 26 (52%) 9 (31%) 7
* Lesions of 5 mm or less, typically palpable, asymptomatic, and nonvisible.† Onset data are available from Valantin et al, 2003 only.[6] Duration was not noted for subcutaneous papules because most were ongoing at study completion.‡ Safety data were collected post hoc for 27 of the patients at approximately 2 years from study start.Source: Sculptra Product Information,
Reconstitution of Poly-L-Lactic Acid
Adherence to recommended reconstitution and injection procedures with poly-L-lactic acid is critical to achieving optimal outcomes and patient satisfaction. Poly-L-lactic acid is supplied as a freeze-dried preparation for injection, with 2 vials per carton -- each containing poly-L-lactic acid, 150 mg. Treatment typically requires injection of the contents of 1 vial of poly-L-lactic acid per cheek area per injection session.

To start, reconstitute the freeze-dried product using 5 mL of diluent (ie, 5 mL of sterile water or 4 mL of sterile water plus 1 mL of lidocaine). Then, set the reconstituted vial aside for 2 hours and administer it within 72 hours. Prior to filling the syringe, shake the vial in order to disperse the polymer.[1] Rolling the syringe between the palms of the hands helps maintain the dispersion of the polymer between injections.

A 5-mL dilution is appropriate for most patients. It affords controllable injections and an even distribution of poly-L-lactic acid. Reconstitution to 3 mL is reserved for the most severe cases of lipoatrophy associated with HIV in male patients. Reconstitution of more than 5 mL does not reduce the effect, but does reduce viscosity and control during the injection.[1]

Injection Techniques
A 26-gauge needle is used to inject poly-L-lactic acid. Unlike line fillers, overcorrection should be avoided. Table 2 summarizes the poly-L-lactic acid administration technique. Although some modification in technique will be needed based on the treated area and the severity of lipoatrophy, key considerations for the successful use of poly-L-lactic acid include placing injections into the deep dermis and subcutaneous layers, avoidance of overcorrection, massaging the area after treatment, and an even distribution of the product.

A mildly to moderately lipoatrophic lower face typically requires 5 mL of product administered using a crisscross and tunneling technique. Each 0.1- to 0.2-mL injection is placed into the deep dermis at the junction with the hypodermis and spaced 0.5 to 1.0 cm from the previous injection (Figure 3). This is followed by massage after 3 to 4 injections.

The temple region responds better to a depot of poly-L-lactic acid than to tunneling. It generally requires 3 to 6 injections per side with 0.05 to 0.1 mL per injection. Unlike the lower face, an injection into the temples should be administered under the muscle just above the periosteum. More advanced injection techniques around the orbits or into the perioral region should not be attempted without sufficient training and knowledge of the injection procedure.

Complete treatment can range from 3 to 6 sessions, depending on lipoatrophy severity and the patient's response. Treatments are separated by 4 to 6 weeks, in order to judge the full cosmetic effect of the previous treatments.

Table 2. Overview of Poly-L-Lactic Acid Injection Technique

  • Product preparation
    • Aseptic technique
    • Reconstitute using 5 mL of diluent (ie, 5 mL of sterile water or 4 mL of sterile water plus 1 mL of lidocaine)
    • Set the reconstituted vial aside for 2 hours
    • Administer within 72 hours
    • Prior to filling the syringe, shake the vial to disperse the polymer
  • Administration
    • 1-mL or 3-mL Luer-Lok syringe and 26-gauge needle
    • Inject 0.1 to 0.2 mL, 0.5 to 1.0 cm apart
    • Place injections into the deep dermis and subcutaneous layers
    • Tunneling (threading) technique into the subcutis
    • Temple region responds better to a depot administered under the muscle just above the periosteum
    • Roll the syringe between the palms of the hands to maintain the dispersion between injections
  • Caution
    • Injections around the orbits or into the perioral region should be attempted after sufficient training and knowledge of the injection procedure
    • Avoid superficial skin injections
    • Avoid overcorrection
  • Post injection
    • Vigorous 2- to 5-minute postinjection massage with moisturizing cream
    • Ice packs
  • Follow-up
    • Multiple treatments at > 4-week intervals
See text for further discussion and considerations


Patient Education
The redness, swelling, pain, and bruising that can appear at treated sites immediately following a treatment session usually resolve in a few hours to a few days. Patients should massage the treated area a few times each day for several days after the treatment session. Within the first 24 hours after treatment, an ice pack should be applied for a few minutes at a time to the treatment area to reduce swelling (Table 3). Excessive sun and UV lamp exposure should be avoided until initial swelling and redness have resolved.

Most patients feel comfortable going back to their normal activities following treatment. Make-up may be applied a few hours after treatment if no complications are present (eg, open wounds or bleeding).

Patients should be warned that it takes several weeks following a treatment session to see the full response and that 3 to 6 sessions are required for a lasting effect (more for patients with HIV). After 24 months, the response to treatment may slowly subside and touch-up treatments can be considered.

Table 3. Patient Education for Poly-L-lactic Acid Treatment

  • Despite small needle size, some patients will experience minor discomfort
    • Dilute poly-L-lactic acid with lidocaine*
    • Use topical anesthetic cream prior to injection
  • Patients may experience initial facial swelling
    • Massage treatment area daily for several days after an injection to ensure even distribution of poly-L-lactic acid
    • Apply an ice pack (do not apply ice directly to the skin) for a few minutes at a time to the treatment area
  • Immediate results are not durable results
    • May take several weeks after a treatment session to see the full effect
    • 3 to 6 sessions are required for a lasting effect (possibly more for patients with HIV)
*This reconstitution is used by the author and was followed by Moyle et al, 2004.[7]
After 2 years of widespread clinical use in the United States and 6 years outside the United States, clinicians have gained practical experience in the use of poly-L-lactic acid for the treatment of facial lipoatrophy in patients with HIV as well as in patients who desire treatment for the facial lipoatrophy that accompanies aging. Poly-L-lactic acid is not simply a line filler. Rather, it is used to achieve facial contouring by creating a tissue response over weeks to months that is characterized by new collagen production.

Complete treatment ranges from 3 to 5 sessions and lasts for approximately 24 months. Re-treatment should be considered as needed, based on each patient's long-term response. Poly-L-lactic acid is well tolerated. However, patients should be told that common procedural events include mild edema and redness. Subacute events are uncommon and may be associated with overcorrection or uneven distribution of the product. Therefore, physician training and understanding of the key points for successful injection of poly-L-lactic acid are important.