Approaches to Treatment of HIV Facial Lipoatrophy

D. Jones, MD

Division of Dermatology, University of California at Los Angeles, Los Angeles, CA, USA

ABSTRACT

HIV-associated facial lipoatrophy has become epidemic among the greater than 1 million HIV-infected individuals living in the United States. Those affected usually have well-controlled HIV disease, and are most often healthy and living productive lives. However, their facial appearance often suggests the opposite and frequently serves as a stigma and psychological burden. Treatment approaches may be divided into three categories: 1) Surgically placed alloplastic, autologous, or synthetic implants; 2) Injection of temporary fillers; 3) Injection of permanent fillers, including liquid injectable silicone. Salient aspects of each treatment are reviewed, along with new techniques and pearls on the correct use of liquid injectable silicone.

Key Words:
HIV, facial lipoatrophy, implants, temporary fillers, permanent fillers

Although HIV facial lipoatrophy is associated with the use of certain antiretroviral drugs, including indinivir (Crixivan®, Merck) and stavudine (Zerit®, Bristol- Myers Squibb), it is clearly not exclusively a drug effect. Risk factors include:

• being Caucasian
• being >40 years of age
• having an HIV infection for >10 years
• having a CD4 of < 100 or < 100 at nadir
• taking indinivir for > 2 years
• any use of stavudine

HIV facial lipoatrophy may be caused by cytokine alterations associated with living long-term with HIV. In patients experiencing rapid progression of HIV facial lipoatrophy and also taking indinivir and/ or stavudine, alternative drug regimens should be considered.

Once lipoatrophy has appeared, it seems that no systemic therapy will reverse the fat loss to an appreciable extent. The most effective treatment is soft tissue augmentation.

Surgical Alloplastic, Autologous, or Synthetic Implants

Autologous fat transfer for HIV facial lipoatrophy has been attempted.1 However, because subcutaneous lipoatrophy also occurs in the abdominal and buttock area, most patients lack adequate donor fat reserves.

Furthermore, transferred fat often continues to dwindle, and corrections often fade over 6-12 months.

Surgical grafting of autologous dermis with attached subcutaneous fat has also been attempted (dermafat grafts). Surgical implantation of cadaveric dermal grafts (such as regenerative tissue matrix, AlloDerm®, LifeCell) provides short-term augmentation, with most grafts becoming reabsorbed within 2 years. Recently, the use of custom-designed silastic implants was described.2 Drawbacks include a rigid feel beneath the skin, and exposure of implant edges should lipoatrophy progress. All of these surgical options are associated with surgical downtime, and high cost, which limit their attractiveness.

Injectable Temporary Fillers

Collagen (bovine or human) or hyaluronic acid may be used to augment the subcutis, but the volumes required to correct HIV lipoatrophy are usually cost prohibitive. The most reasonable temporary filler for HIV facial lipoatrophy may be the newly approved poly-L-lactic acid (Sculptra®, Dermik). Poly-L-lactic acid is a synthetic absorbable material that stimulates a fibroproliferative response upon injection in the subcutis. Often five or more treatments, spaced at 2-week intervals, are required to treat HIV facial lipoatrophy. Optimal corrections may persist for 1-2 years, at which point reinjection is necessary. The biggest drawback, as with other temporary fillers, is the high cost. Treatments (2 vials per treatment) generally will cost the patient $1500 USD or more per treatment session.

Obtaining insurance reimbursement is often difficult or impossible, and patients often find
the treatments financially out of reach. Dermik has recently instituted a patient assistance program whereby patients making under $40,000 yearly may qualify for free product, but the patient is still responsible for the physician fee, which is often $500 or more per injection session. It should also be noted that in European studies, up to 44% of patients developed palpable but non-visible subcutaneous micronodules, which tended to spontaneously resolve.3 Persistent granulomatous dermal papules have been observed, and may be caused by inadvertent intradermal injection.1

Injectable Permanent Fillers

Among patients with HIV facial lipoatrophy, there has been great demand for permanent injectable fillers. At this point, the only injectable permanent filler legally available in the United States is liquid injectable silicone. Although not specifically approved for soft tissue augmentation, Silikon™ 1000 is FDA-approved for intraocular injection for tamponade of retinal detachment, and may be used legally on an off-label basis for subdermal volume restoration. Recently, Silikon™ 1000 was described as a safe and effective method for treatment of HIV facial lipoatrophy, although long term safety and efficacy have yet to be established.4

There is controversy surrounding the use of liquid injectable silicone. Critics believe that liquid injectable silicone is inherently unpredictable, with an unacceptably high incidence of complications such as nodule formation or inflammatory reactions appearing sometimes many years after injection.4 BB Advocates, however, rely on a wealth of anecdotal data4 to support the claim that liquid injectable silicone is safe and predictable as a soft tissue filler, and that complications are very rare as long as the following three rules are obeyed:

1. Use pure injectable grade silicone which is US FDA approved for injection into the human body. It is noteworthy that prior to the mid 1990s, no such injectable grade silicone existed for routine use. An analysis of liquid injectable silicone oils often used for tissue augmentation in the 1960s, 1970s, and 1980s revealed an excess of impurities, which may account for instances of inflammatory reactions related to silicone injections during that time.
2. Adhere to strict serial puncture microdroplet technique, with injections only into the subdermal plane or deeper. Intradermal injections are to be avoided, as dermal swelling, erythema and ridging may result. Silikon™ 1000 should be injected through a 30G Max-Flo® needle (Richard James Development) with approximately 0.01cc injected with each needle insertion, at approximately 2- 5mm intervals. Over a period of several weeks, a limited foreign-body response causes each microdroplet to be enveloped by a collagenous capsule. This promotes further tissue augmentation and allows each microdroplet to be anchored in place, obviating the risk of migration.
3. Inject limited volumes at monthly intervals. Injection of large volumes all at once increases the risk for migration along tissue planes, as a bolus of silicone oil will not immediately anchor itself to the surrounding tissue. The protocol for HIV lipoatrophy calls for no more than 2ccs to be injected at monthly intervals. Approximately three treatments will be required for each stage on the Carruthers’ lipoatrophy severity scale.4 Therefore, a stage 1 patient will require an average of three treatments, a stage 2 patient an average of six treatments, and a stage 3 patient an average of nine treatments. This is merely a guideline, but is useful in counseling patients during the consultation process. Patients should also be counseled that the correction proceeds very gradually, but that eventual optimal correction is expected in vast majority of patients.

Injection Pearls for Liquid Injectable Silicone

After a consultation where risks, benefits, indications and options of liquid injectable silicone are reviewed, appropriate informed consent and high quality photos should be obtained. The patient should refrain from taking aspirin, NSAIDS, and vitamin E for 7-10 days prior to treatment.

The patient’s face is cleansed with povidone iodine or an antibacterial cleanser. Topical anesthetic cream (benzocaine 20%, lidocaine 6%, tetracaine 4%) is applied under plastic occlusion to the areas to be treated for at least 30 minutes. The topical anesthetic is
then removed with gauze. Using a new fine tip Sharpie black pen, areas to be injected are carefully outlined. This is perhaps the most important, and potentially the most difficult, aspect of treatment planning.

Areas of depression at rest often tend to become elevated when the patient smiles, depending on tissue redundancy. Therefore, the author finds it most useful mark the patient first in a smiling position. While the patient smiles, the areas of greatest depression are carefully outlined with the pen in the malar, pre-masseteric, pre-auricular, and temporal areas. Then, with no smile, areas of deepest depression are carefully marked. It is important to assess where areas of depression at rest may be potentially overcorrected in such a way that excessive elevation occurs while smiling. In those areas, appropriate caution and conservative volumes should be employed to avoid overcorrection.

Once marking is complete, injections may begin. Silikon™ 1000 should be injected strictly into the subdermal plane or deeper. The most common mistake among novice injectors is injecting intradermally, which is likely to produce a suboptimal result and complications including dermal edema and erythema. Injections should be performed at 2-5mm intervals throughout the entire marked area. Volumes should be limited to 2cc total per treatment session. A second pass may be taken in the deepest areas, about 5mm deeper than the first pass. Generally, there is mild, even swelling after the procedure which the patient frequently enjoys, and which resolves within 3-7 days.

Many patients like the slow, gradual correction, as the transformation is not drastic and therefore not obvious to those with whom they interact more frequently.

Performed correctly, injection of liquid injectable silicone offers an extremely cost effective, very natural feeling, and durable correction of HIV facial lipoatrophy. Currently, about 1000 patients have been treated at four centers using this protocol, with no severe adverse events over 4 years.4 However, patients should be counseled that this is still considered an investigational treatment, and that longer term data are necessary to more completely understand the longterm disposition of this permanent filler in the HIV patient.

References

1. Jones D. HIV Facial lipoatrophy: causes and treatment options. Dermatol Surg, in press.
2. Binder WJ, Bloom DC. The use of custom-designed midfacial and submalar implants in the treatment of facial wasting syndrome. Arch Facial Plastic Surg 6(6):394-7 (2004 Nov).
3. Valantin MA, Aubron-Oliver 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).
4. Jones DH, Carruthers A, Orentreich D, et al. Highly purified 1000-cSt silicone oil for treatment of human immunodeficiency virus-associated facial lipoatrophy. Dermatol Surg 30(10):1279-86 (2004 Oct).