Dermatology Online Journal
Treatment of HIV-associated facial lipoatrophy with Radiance FN™ (Radiesse™)
- Author(s): Comite, Stephen L, MD
- Liu, Judy F
- Balasubramanian, Suprina
- Christian, Marisa A
- et al.
Treatment of HIV-associated facial lipoatrophy with Radiance FN™ (Radiesse™)
From the Mount Sinai Department of Dermatology1, New York, NY. email@example.com
Stephen L. Comite MD1, Judy F Liu, Suprina Balasubramanian, and Marisa A Christian
Dermatology Online Journal 10 (2): 2
HIV treatments frequently include the administration of Highly Active Antiretroviral Therapy (HAART) to combat the disease; although no conclusive evidence exists, it has been suggested that the HAART regimen may lead to facial lipoatrophy, exemplified by fat loss from facial areas, most notably the cheeks. Lipoatrophy can cause severe psychosocial consequences because it can be an identifying marker of HIV infection. Calcium hydroxylapatite (Radiance FN™, recently renamed Radiesse™) has been postulated to be a long-lasting, biocompatible filler that does not ossify, migratem or calcify. We present three patients with HIV-associated lipoatrophy who were treated with Radiance FN™. Touch-up treatments were performed 1 month later for two patients. The percentage of improvement following the initial treatment ranged from 75 to 90 percent. Although there has been some loss of improvement over time, there has been significant persistence for up to 9 months. No complications have occurred, and patients were highly satisfied with treatment results. Our experience with Radiance FN™ has shown it to be a potentially valuable tool for treating facial lipoatrophy.
Since the introduction of or Highly Active Antiretroviral Therapy (HAART) in 1996, the decrease in mortality rates of HIV patients  has been accompanied by an increase in morphological and metabolic changes known as lipodystrophy syndrome. Lipodystrophy has been characterized by loss of fat, or lipoatrophy, in the face or limbs, as well as fat accumulation, or lipohypertrophy, in the posterior neck, breasts, and trunk . It was first described as a syndrome in 1998 linked to protease inhibitors, but since then studies have found that both protease inhibitors and nucleoside analog retroviral therapy are associated with lipodystrophy [3, 4]. Different theories have arisen regarding the pathophysiology of lipodystrophy syndrome, and little has been proven of its causes. However, the psychosocial effects on patients are certain. The gradual fat redistribution and resulting disfigurement has become a stigmatizing feature of HIV, and often causes emotional distress for the affected patient . This resulting anguish can serve as a factor for delaying as well as discontinuing antiretroviral therapy . These decisions in turn lead to dire consequences for the patient in their HIV treatment, as well as little relief for the lipodystrophy they hope to reverse .
Although lipodystrophy may affect several areas of the body, the face most obviously and publicly exhibits the wasting effects of HIV, and poses the greatest risk of stigma . Treatment of lipoatrophy of the face, therefore, may provide the greatest psychological relief for the patient. Although there is no known cure for lipodystrophy , some patients have turned to pharmacologic approaches such as glitazones [9, 10, 11, 12, 13, 14, 15, 16], switching their HAART regimens [17, 18, 19, 20, 21], structured interruption of HAART  or GHRH, a growth hormone secretogogue . Other patients have resorted to surgical procedures and injections for softening the gaunt facial features characteristic of the disease process. Methods of facial contour restoration have included dermal-fat grafts and fat injections [23, 24, 25], submalar silicone implants , liquid injectable silicone , polylactic acid or PLA injections (Newfill™, Sculptra™) [28, 29, 30, 31], collagen, hyaluronic acid fillers (Restylane™) , and calcium hydroxylapatite (Radiance FN™, recently renamed "Radiesse™").
One of the newest soft-tissue fillers is Radiance FN™. This biocompatible implant filler consists of calcium hydroxylapatite (CaHa) microspheres, 35 mm in diameter, suspended in an aqueous gel carrier consisting of water, glycerin, and sodium carboxymethylcellulose. Once injected, the CaHa particles theoretically form a scaffold for the developing soft tissue that gradually replaces the disintegrating gel carrier. Fibroblasts grow directly on the surface of the CaHa particles at the injection site and anchor the microspheres in place, resulting in injection site tissue of consistency similar to that of the surrounding tissue. As a result, the material does not react, extrude, or migrate [33, 34, 35].
Because it is the major mineral component of bone, CaHa should not provoke an immune-system reaction [36, 37]. In addition, because calcium and phosphate are metabolized in the body, resorption of the minerals should not cause systemic toxicity . When placed into soft tissue separate from periosteum, CaHa does not cause heterotopic bone formation [33, 34, 38].
Radiance has been approved by the FDA as a soft-tissue marker for radiological procedures, for oral-maxillofacial defects, and for voca-cord insufficiency and is being used for urinary incontinence [36, 37, 39]. Although Radiance FN™ has been approved in Europe as a soft tissue filler, it has not been approved for cosmetic facial use in the USA by the FDA, but can be legally used off-label. In two studies, Radiance FN™ was used as a cosmetic filler in various facial areas, and results were shown to be immediate with minimal side effects and high patient satisfaction [40, 41]. Radiance FN™ in various forms has been used for over 15 years in orthopedic and reconstructive surgery and in dentistry . Radiance can be useful in treating bone deficiencies whether a result of congenital deformities or post-traumatic conditions [42, 43]. Radiance FN™ has a good safety profile [42, 44]. Studies have shown its excellent biocompatibility. Its longevity has been shown in some cases to persist over 5 years . In addition, there has been no evidence of calcification, ossification or migration, qualifying it as a potentially valuable soft tissue filler [36, 40].
We report on our experience using Radiance FN™ in the treatment of three patients with facial lipoatrophy. Improvement rates of 75-90 percent were achieved on the basis of physician observations and photos and persisted up to 9 months.
Radiance FN™ information was given to and reviewed with each patient. The patients were informed that the use of Radiance FN™ for treatment of lipoatrophy would be considered off-label. All patients were extensively counseled, and a consent form for each was reviewed and signed. Patients were also advised that touchups of Radiance FN™ were generally necessary 2-4 weeks after the initial treatment and that the longevity of Radiance FN™ was not yet known.
Patients were warned that Radiance FN™ might appear on dental X-rays. Radiance FN™ is radio-opaque; however, it should not interfere with radiological procedures because Radiance FN™ has a lower density than bone. We advised our patients that if they need X-rays that it is recommended to notify doctors or dentists if they are unfamiliar with the radio-opacity of this treatment. In addition, Radiance FN™ should not be injected into areas of active infection.
For each of the three patients, injection areas were prepped with alcohol. Subsequently, less than 2 cc of 1 percent lidocaine with epinephrine was used inferiorly and laterally to the injection sites to anesthetize the margins of the lipoatrophic area so as not to distort the site to be treated. To describe the level of a patient's lipoatrophy, we used the grading system proposed by James, Carruthers, and Carruthers . In addition to the 1 percent lidocaine, Valium 10 mg was used as an anxiolytic by patient 1, who was accompanied home by an escort after the treatment. We have not found nerve blocks to be necessary for treatment of lipoatrophy.
A Radiance FN™ syringe with a 27-gauge, 1-inch needle was inserted at a 15-30-degree angle at approximately the dermal to subcutaneous junction or slightly below. A fanning and cross-hatching technique allowed the threading of Radiance FN™ on withdrawal. If localized areas needed additional Radiance FN™, an RJ Max flow 30-gauge 0.4 inch needle was used, again with injection upon withdrawal. Once Radiance FN™ was injected, the patient's cheek was massaged, if necessary, to ensure even distribution of the filler. With experience, minimal massage was necessary. After treatment, minimal to moderate erythema at the injection sites lasted from several hours up to a few days, but was not clinically significant. If desired, cover-up makeup can be used to camouflage the area treated. If an area became erythematous after a few minutes of treatment, we did not treat the area further during that session, with the exception of massaging if indicated.
Radiance FN™ feels soft and minimally palpable after treatment and is generally not palpable by the 2-week followup. During treatment, most patients experienced throbbing pain, which peaks and then resolves spontaneously after a few minutes. Analgesics have not been necessary after treatment. We prefer treating conservatively at the initial visit as do previous investigators, [40, 41] and do not recommend overcorrection. A less extensive touch-up treatment is often indicated at a 2-4 week follow-up visit. All patients recovered fully and no complications occurred. Each patient was followed every few weeks. Photos were taken before and after each treatment as well as at each follow-up visit to assess improvement. Assessments of the patients' improvement were performed by the senior author after clinical evaluation and after comparison with the pretreatment photos and were approximated but correlated reasonably well with patient self-assessments.
Patient 1, a 49-year-old African-American male, who has a history of HIV since 1987, developed lipodystrophy in approximately 2000. His HAART regimen during time of Radiance FN™ treatment consisted of Amprenavir, Ritonavir, Tenofovir DF, and Abacavir. He exhibited extensive facial lipoatrophy, grade 3 according to the Carruthers scale.  He was treated with 1.7 cc's of Radiance FN™ in the right cheek, 1.5 cc's in the left cheek, and 0.25 cc's in the nasolabial folds bilaterally, for a total of 3.8 cc's of Radiance FN™ overall. The percentage of improvement was observed to be 85-90 percent. A touch-up procedure was performed 1 month later and included 0.2 cc's in the right cheek, and 0.4 cc's in the left cheek, for a total of 0.6 cc's of Radiance FN™. A week following the second treatment, patient 1 reported the improvement of his lipoatrophy to be 90 percent. No subsequent treatment with Radiance FN™ has been needed to the treated areas as of 6 months since the last procedure, and the patient's improvement has been maintained at 85-90 percent.
Patient 2, a 55-year-old Caucasian male, was diagnosed with HIV in 1989. His HAART regimen has included AZT, Epivir, Zerit, Viracept, Sustiva, Norvir, Fortovase, Viramune, and Combivir. After the onset of lipodystrophy in 2000, the patient had attempted correction with two treatments of collagen (Zyplast), which were successful but short-lived. By the time of his Radiance FN™ treatment, 3months later, the correction with collagen had completely disappeared. During his Radiance FN™ treatment, Patient 2 was taking Viramune and Combivir. Patient 2's extent of lipoatrophy at baseline was the most severe of our patients treated, grade 4 on the Carruthers scale. Patient 2's initial treatment with Radiance FN™ was 2.85 cc in total, with 1.25 injected into the right cheek, and 1.6 cc injected into the left cheek. He estimated his improvement to be 85 percent after his initial treatment. At follow-up treatment 1 month later, he required injection of 0.3 cc of Radiance FN™ in the left cheek, and 0.2 cc in the right cheek, totaling 0.5 cc. At 7 months after the initial treatment and 5 months after the touch-up procedure, the improvement was estimated by the physician to be about 55 percent.
|Figure 1||Figure 2|
|Patient 3 pretreatment, facial lipoatrophy, full face and right side.|
|Figure 3||Figure 4|
|Immediately after treatment with Radiance FN (Radiesse) for facial lipoatrophy, full face and right side.|
|Figure 5||Figure 6|
|Patient #3 2 months after treatment with Radiance FN (Radiesse) for facial lipoatrophy, full face and right side.|
|Figure 7||Figure 8|
|Patient #3 9 months after treatment with Radiance FN (Radiesse) for facial lipoatrophy, full face and right side.|
Patient 3 is a 44-year-old Caucasian male who was diagnosed with HIV in 1996 and first showed signs of lipoatrophy in 2000. The patient's HAART medications included Virend and Combivir during the treatment of his lipodystrophy with Radiance FN™. The extent of patient 3's lipoatrophy at baseline was Carruthers grade 3 (Figs. 1 and 2). His sole treatment consisted of 2 cc of Radiance FN™, with about 1 cc injected into each cheek (Figs. 3 and 4). The initial level of improvement was estimated to be 80 percent, and no follow-up treatment was necessary. Patient 3's degree of improvement was approximated at 75 percent, as evaluated by the physician 2 months after the initial treatment (Figs. 5 and 6). At 9 months after treatment, although increased lipoatrophy was noted in the right cheek, the estimated improvement was approximately 70 percent overall (Figs. 7 and 8).
Prior to the use of protease inhibitors (PI) and nucleoside reverse transcriptase inhibitors (NRTI) in HAART as standard care of HIV, the wasting syndrome that was associated with HIV dissipated lean body cell mass, while maintaining the patient's adipose tissue . The wasting syndrome of the HAART era is associated with adipose tissue loss while leaving body cell mass unaffected, and has become known as lipoatrophy. Lipoatrophy targets the face, arms, and legs, and is one aspect of the fat distribution abnormalities of lipodystrophy syndrome .
Although lipodystrophy is not the harbinger of morbidity that the wasting syndrome of HIV was before the advent of HAART, lipodystrophy is now one of the most distressing attributes of HIV that patients must endure. Aside from the strongly associated medical conditions that include type-2 diabetes mellitus, insulin resistance, dyslipidemia, lactic acidemia, hypertriglyceridemia and reduced high-density lipoprotein cholesterol levels [47, 48], lipodystrophy has had major psychosocial effects on patients, causing depression, self-consciousness, and loss of self-esteem. Emotional distress, diminished social life, and reduced libido have brought about quality-of-life issues as patients become anxious over the distortion of their features and fear the manifestations of lipodystrophy as indicators of their HIV status . As a result, lipodystrophy has been one of the factors for either delaying the start of or failing to adhere to HAART, which has been implicated as the cause of lipodystrophy . However, delaying the introduction of HAART can further complicate treatment, as patients have higher baseline HIV viral load and lower CD4 cell count. The cessation of HAART does not reverse the ravages of lipodystrophy  and poses the more serious risks of increase in drug-resistant strains of HIV, opportunistic infections, and increased viral load .
Although the etiology of lipodystrophy is unknown, its causes have been strongly linked to protease inhibitors and nucleoside reverse transcriptase inhibitors. Protease inhibitor therapy has been associated mainly with insulin resistance and hypercholesterolemia while nucleoside analogue therapy has been linked to lactic acidemia associated with mitochondrial toxicity, the two treatment types, however, may interact synergistically . Protease inhibitors target the catalytic region of HIV-1 protease, which is homologous with regions of two human proteins that regulate lipid metabolism: cytoplasmic retinoic-acid binding protein type 1 (CRABP-1) and low-density lipoprotein-receptor-related protein (LRP). Thus, it has been hypothesized that PIs interfere with these proteins and impair the regulation of peripheral adipocyte differentiation and apoptosis as well as triglyceride clearance, resulting in hyperlipidemia, insulin resistance, and type-2 diabetes [3, 51].
Initially, PIs alone were implicated for lipoatrophy, but studies have shown that lipoatrophy occurs also in patients that received NRTI alone [4,52]. NRTI has been implicated as another factor for lipoatrophy through mitochondrial toxicity, as nucleoside analogues inhibit to a varying extent the enzyme responsible for mtDNA replication, DNA polymerase _. As a result, nucleoside analogues have been found to inhibit adipogenesis while promoting lipolysis .
Although ongoing studies are still being performed to determine the physiopathology of lipodystrophy, treatments for lipoatrophy are limited. Pharmacological solutions have included glitazones, switching HAART regimens, and structured HAART interruption.
Glitazones, also known as thiazolidinediones, are a class of oral antidiabetic drugs that enhance insulin sensitivity in target tissues. Glitazones have been known to alter fat distribution in non-HIV lipodystrophy, prompting studies on its effects on HIV-induced lipodystrophy [14, 53, 54]. Studies have provided mixed results as to the ability of glitazones to affect lipoatrophy, and the studies that have shown reversal of lipoatrophy report only subtle improvement [9 10, 12, 13, 14, 15, 16, 55].
Because PIs have been found to be a major factor in inducing lipodystrophy, switch studies have been conducted to evaluate the effects of altering patient HAART regimens and switching from PIs to Abacavir, Combivir, Nevirapine, or Efavirenz. Some studies have shown slight improvements in lipoatrophy as well as improved adherence to HAART regimen and improved quality of life [17, 21, 56, 57, 58]. However, other studies have either come to no conclusions or have shown no improvements in body fat mass by switching from protease inhibitors to other HAART drugs [21, 57, 59, 60].
Another alternative patients have taken to decrease the toxicities associated with HAART has been the structured interruption of drug treatment. Although some symptoms of toxicity were improved, such as decrease in total cholesterol, LDL cholesterol, and triglycerides, lipodystrophy symptoms were not shown to reverse. There has been no evidence of significant changes in anthropometric measurements as a result of structured interruption of HAART .
A growth hormone secretogogue, GHRH, has recently been used in a double-blinded, placebo controlled study for the treatment of lipodystrophy . Although this medication showed promised in treating peripheral lipodystrophy, there was apparently no improvement in facial lipoatrophy.
Despite progress in studies of pharmacological treatments of lipoatrophy, perceived improvement by patients and doctors has not been as great as that shown for cosmetic procedures and surgery. Several cosmetic and surgical techniques have been attempted, including fat-graft transfers, fat injections, submalar silicone implants, silicone injections, collagen injections, poly-L-lactic acid or PLA (New-Fill™, Sculptra™) injections, and Restylane™ injections. Fat-graft transfer and fat injections involve Coleman's technique in the harvesting of the patient's fat. In fat-graft transfer, the harvested fat is placed onto the malar pockets. Overcorrection is required, since an estimated 50 percent of volume was anticipated to be lost after the operation. In one study, results persisted for 1-2 years of followup . In another report, fat grafts persisted after 6 months .
Fat injections involve centrifuging the fat and reinjecting it into the lipoatrophic areas. Hospitalization for 2 days is necessary, and patients are given antibiotics to avoid infection. The advantage of these procedures is that autologous fat will not react adversely . However, lipoaugmentation is not always a viable treatment because severely lipoatrophic patients do not have sufficient fat to harvest. The surgical procedures require greater recovery time and risk of infection for the patient, and greater risk of HIV exposure on the part of the physician. In addition, the transferred fat may be lost through further lipoatrophic processes.
Another group  has used submalar silicone implants alone and in conjunction with both collagen and autologous fat tissue supplementation. Three patients were presented that had submalar augmentation with silicone implants. The procedure was performed under local anesthesia. Two patients required further augmentation in the nasolabial folds with collagen or autologous fat, and 2 weeks after the operation, one patient required repositioning of one of the implants secondary to reported malposition. At 15 months after the operation, the patient experienced progressed lipoatrophy and required additional collagen and fat autologous tissue augmentation. Patients were followed for a mean of 15 months.
Liquid injectable silicone (LIS) has been reported to have good results, but only one case has been published . In this procedure, 1000-centistoke silicone fluid was injected into the lipoatrophic areas. Liquid injectable silicone was administered monthly for eight visits. Like Radiance FN™, LIS is an off-label indication for soft-tissue augmentation. Silicone provides relatively permanent correction; however, the success of LIS is highly dependent on physician technique, because overcorrection and mistakes can be difficult to ameliorate . In addition, the permanence of LIS may be a disadvantage should a viable treatment for lipodystrophy become available in the future. LIS requires only topical anesthesia. However, as a foreign substance, it is more likely to be rejected and has been reported to migrate, though the impurities in previous nonmedical grade forms of silicone may be to blame. In addition, silicone has been reported to form silicone granulomas [61-67]. The microdroplet technique used in the distribution of LIS requires more treatments than other fillers, and a longer span of time to show significant improvement.
Aside from collagen, for which there are no published studies in its treatment of HIV-associated lipoatrophy, other synthetic fillers have been used for the treatment of lipoatrophy, one of which is poly-L-lactic acid (PLA), a biocompatible and immunologically inert synthetic polymer (Sculptra in the USA, Newfill in Europe). The material apparently works through a locally induced reaction, after which there is a progressive increase in collagen deposition as the bioactive material is degraded and resorbed. Poly-L-lactic acid has been safely used in orthopedic and maxillofacial procedures since the mid-1990s and was approved in Europe in 1999 for the cosmetic correction of scars and wrinkles [16, 27, 28]. As we were in the process of finalizing this paper, PLA (Sculptra™) was approved in the USA for the treatment of HIV related lipoatrophy. One advantage of PLA is that it is biodegradable. Also, no allergy testing is necessary. Sculptra™ needs to be reconstituted from powder using water and possibly lidocaine. Disadvantages of PLA treatment of lipoatrophy include the necessity for multiple sessions of injections. Generally, the procedure requires several sets of injections, generally from two to six sessions spaced at least 2 weeks apart. The injections have so far shown to trigger enough collagen production to last for 12-18 months, so longevity is very good [28, 29]. PLA treatment has been reported to frequently cause nodules, although apparently they are generally not clinically significant. There is one report of a Newfill granuloma on biopsy, but it is unclear whether this granuloma is related to an injection of an unknown filler in the same place 7 years prior. Further studies are necessary to examine the long-term and lasting effects of PLA, but it has been used extensively and safely in Europe for years for both HIV-related lipoatrophy and non-HIV related rhytides, scarring and atrophy.
One filler that recently became FDA approved for the treatment of rhytides is Restylane, and has been used previously by two authors in the treatment of HIV-associated lipoatrophy [30,68]. Restylane consists of a clear, biodegradable nonanimal stabilized hyaluronic acid gel (NASHA); hyaluronic acid is a naturally occurring polysaccharide present in skin, subcutaneous, and connective tissues that does not require preliminary skin testing in its pure form . Another hyaluronic acid product made from rooster combs, hylaform, is also FDA approved. Although there have been few cases of adverse events, studies have reported transient redness, red spots, and swelling at the injection site [70,71]. Cutaneous hypersensitivity to hyaluronic acid gel, long-term abscess-like complications , contact dermatitis , granulomatous lip reaction  and arterial embolization  have also been reported. Restylane is biodegradable and its longevity is likely equal to or greater than Zyplast.  Restylane has also been used extensively in Europe and other countries for many years.
Radiance FN™, with its biocompatibility, long-lasting potential, and lack of migration, ossification, or need for special instrumentation, can be considered as an alternative option for the treatment of HIV-associated lipoatrophy. No allergy testing is necessary. No overcorrection, or surgical procedure is required as in lipoaugmentation, and only a brief recovery period is required. Radiance FN™ is long-lasting but not permanent, potentially providing long-term relief of lipoatrophy while allowing for flexibility in treatment. The only complications reported were nodules, which have been reported by authors to occur solely in lip- and tear-trough regions, locations not generally relevant to HIV lipoatrophy [40,41,78]. These nodules were correctable either with injection of cortisone or with incision and removal of the nodules .
We advised our patients that Radiance FN™ might interfere with standard dental radiological films. One patient studied, however, had a computerized tomography (CT) scan performed 7 months after lip augmentation with Radiance FN™ to assess calcium deposition and possible implant migration . Although the image showed calcific density throughout the expected course of the upper and lower lip, no adenopathy was observed nor was there evidence of remote calcium deposition. Dental x-rays in the same patient showed no interference in standard radiography.
One prominent physician objects to the use of Radiance FN™ because its use in the lips can cause nodules and because permanent fillers may cause problems years later . Radiance FN™ as well as PLA (Sculptra, Newfill) may perhaps be characterized, however, as intermediate fillers, as both evidently resorb with time. Further studies are necessary to evaluate the longevity of Radiance FN™ as well as long-term adverse reactions.
In our three clinical cases, patient satisfaction was achieved in from one to two treatments, and patient assessment of initial improvement ranged from 75-90 percent. In our experience, injection of Radiance FN™ can sometimes be more painful than injection of collagen or Restylane, and for this reason, patient 1 used an anxiolytic and needed an escort home. The administration of an anxiolytic has allowed the Radiance FN™ treatment to proceed with minimal discomfort and excellent patient compliance. Anxiolytic medications were not necessary for minor touch-up procedure. No complications have occurred in our patients, except for mild erythema at the injection sites for a few hours to a few days after treatment, resolving spontaneously. Radiance FN™ did not have the same duration in patient 2, the patient with the most severe lipoatrophy, as compared with the other patients. This may be because of the lack of existing tissue framework, which may be necessary to produce increased longevity for Radiance FN™. Results can be confounded by progression of lipoatrophy and possibly by adjustment of HIV medication regimen. The approximate 70 percent persistence overall in one patient after 9 months of treatment is encouraging. All three patients on subsequent followup have attested to the improvement in self-image and confidence after their Radiance FN™ treatments. They have received compliments on the appearance of their general health and have been pleased with the results.
Although questions remain regarding the pathophysiology of lipodystrophy, and a cure is yet to be found, there are still avenues lipoatrophy patients can take to relieve their condition. Currently, studies on drug-treatment options such as glitazones, switch therapy, and interruption of HAART drugs have not shown conclusive evidence or impressive results of improving lipoatrophy. Surgical procedures and fillers such as autologous fat, collagen, and especially PLA (Sculptra, Newfill), silicone, hyaluronic acid (Restylane, Hylaform), and calcium hydroxylapatite (Radiance FN™ or Radiesse™) are capable of dramatic improvement in normalizing facial contours.
Our experience with Radiance FN™ offers evidence of its excellent viability as an aesthetic soft-tissue filler and treatment for HIV-associated lipoatrophy. For patients suffering from the psychosocial repercussions of lipoatrophy, Radiance FN™ is another option to consider for relief from a potentially stigmatizing condition, and a safer alternative to discontinuing HAART. Additional studies should be conducted to further investigate the use of Radiance FN™ in the treatment of lipoatrophy.
References1. Palella FJ, Jr., Delaney KM, Moorman AC, et al. Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. HIV Outpatient Study Investigators. N Engl J Med 1998;338(13):853. PubMed
2. Carr A, Samaras K, Thorisdottir A, et al. Diagnosis, prediction, and natural course of HIV-1 protease-inhibitor-associated lipodystrophy, hyperlipidaemia, and diabetes mellitus: a cohort study. Lancet 1999;353(9170):2093. PubMed
3. Carr A, Samaras K, Burton S, et al. A syndrome of peripheral lipodystrophy, hyperlipidaemia and insulin resistance in patients receiving HIV protease inhibitors. Aids 1998;12(7):F51. PubMed
4. Saint-Marc T, Partisani M, Poizot-Martin I, et al. A syndrome of peripheral fat wasting (lipodystrophy) in patients receiving long-term nucleoside analogue therapy. Aids 1999;13(13):1659. PubMed
5. Mauss S. [HIV-associated lipodystrophy syndrome. Stress for the psyche and heart]. MMW Fortschr Med 2002;144 Suppl 1:20. PubMed
6. Duran S, Saves M, Spire B, et al. Failure to maintain long-term adherence to highly active antiretroviral therapy: the role of lipodystrophy. Aids 2001;15(18):2441. PubMed
7. Hatano H, Miller KD, Yoder CP, et al. Metabolic and anthropometric consequences of interruption of highly active antiretroviral therapy. Aids 2000;14(13):1935. PubMed
8. Garg A. Acquired and inherited lipodystrophies. N Engl J Med 2004;350(12):1220. PubMed
9. Yki-Jarvinen H, Sutinen J, Silveira A, et al. Regulation of plasma PAI-1 concentrations in HAART-associated lipodystrophy during rosiglitazone therapy. Arterioscler Thromb Vasc Biol 2003;23(4):688. PubMed
10. Sutinen J, Hakkinen AM, Westerbacka J, et al. Rosiglitazone in the treatment of HAART-associated lipodystrophy--a randomized double-blind placebo-controlled study. Antivir Ther 2003;8(3):199. PubMed
11. Sutinen J, Kannisto K, Korsheninnikova E, et al. Effects of rosiglitazone on gene expression in subcutaneous adipose tissue in highly active antiretroviral therapy-associated lipodystrophy. Am J Physiol Endocrinol Metab 2004. PubMed
12. Walli R, Michl GM, Muhlbayer D, et al. Effects of troglitazone on insulin sensitivity in HIV-infected patients with protease inhibitor-associated diabetes mellitus. Res Exp Med (Berl) 2000;199(5):253. PubMed
13. Calmy A, Hirschel B, Hans D, et al. Glitazones in lipodystrophy syndrome induced by highly active antiretroviral therapy. Aids 2003;17(5):770. PubMed
14. Gelato MC, Mynarcik DC, Quick JL, et al. Improved insulin sensitivity and body fat distribution in HIV-infected patients treated with rosiglitazone: a pilot study. J Acquir Immune Defic Syndr 2002;31(2):163. PubMed
15. Carr A, Workman C, Carey D, et al. No effect of rosiglitazone for treatment of HIV-1 lipoatrophy: randomised, double-blind, placebo-controlled trial. Lancet 2004;363(9407):429. PubMed
16. Hadigan C, Yawetz S, Thomas A, et al. Metabolic effects of rosiglitazone in HIV lipodystrophy: a randomized, controlled trial. Ann Intern Med 2004;140(10):786. PubMed
17. Leen CL. Perspectives on HAART: switch maintenance therapy. Int J STD AIDS 2003;14(9):577. PubMed
18. Ruiz L, Negredo E, Domingo P, et al. Antiretroviral treatment simplification with nevirapine in protease inhibitor-experienced patients with hiv-associated lipodystrophy: 1-year prospective follow-up of a multicenter, randomized, controlled study. J Acquir Immune Defic Syndr 2001;27(3):229. PubMed
19. Murphy RL, Smith WJ. Switch studies: a review. HIV Med 2002;3(2):146.
20. Lafeuillade A, Clumeck N, Mallolas J, et al. Comparison of metabolic abnormalities and clinical lipodystrophy 48 weeks after switching from HAART to Trizivir versus continued HAART: the Trizal study. HIV Clin Trials 2003;4(1):37. PubMed
21. John M, McKinnon EJ, James IR, et al. Randomized, controlled, 48-week study of switching stavudine and/or protease inhibitors to combivir/abacavir to prevent or reverse lipoatrophy in HIV-infected patients. J Acquir Immune Defic Syndr 2003;33(1):29. PubMed
22. Koutkia P, Canavan B, Breu J, et al. Growth Hormone- Releasing Hormone in HIV-Infected Men with Lipodystrophy. JAMA 2004;292:210-218.
23. Levan P, Nguyen TH, Lallemand F, et al. Correction of facial lipoatrophy in HIV-infected patients on highly active antiretroviral therapy by injection of autologous fatty tissue. Aids 2002;16(14):1985. PubMed
24. Caye N, Le Fourn B, Pannier M. [Surgical treatment of facial lipoatrophy]. Ann Chir Plast Esthet 2003;48(1):2. PubMed
25. Strauch B, Baum T, Robbins N. Treatment of human immunodeficiency virus-associated lipodystrophy with dermafat graft transfer to the malar area. Plast Reconstr Surg 2004;113(1):363. PubMed
26. Talmor M, Hoffman LA, LaTrenta GS. Facial atrophy in HIV-related fat redistribution syndrome: anatomic evaluation and surgical reconstruction. Ann Plast Surg 2002;49(1):11. PubMed
27. Orentreich D, Leone AS. A case of HIV-associated facial lipoatrophy treated with 1000-cs liquid injectable silicone. Dermatol Surg 2004;30(4 Pt 1):548. PubMed
28. Valantin MA, Aubron-Olivier C, Ghosn J, et al. Polylactic acid implants (New-Fill)(R) to correct facial lipoatrophy in HIV-infected patients: results of the open-label study VEGA. Aids 2003;17(17):2471. PubMed
29. 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 2004;5(2):82. PubMed
30. Cheonis N. New-Fill to treat facial wasting. Beta 2002;15(2):10. PubMed
31. Onesti MG, Renzi LF, Paoletti F. Use of Polylactic acid in face lipodystrophy in HIV positive patients undergoing treatment with antiretroviral drugs (HAART). Acta Chir Plast. 2004;46(1):12-5
32. Walther RA. [Facial lipodystrophy in patients with HIV infections troublesome to treat]. Lakartidningen 2002;99(39):3826. PubMed
33. Drobeck HP, Rothstein SS, Gumaer KI, et al. Histologic observation of soft tissue responses to implanted, multifaceted particles and discs of hydroxylapatite. J Oral Maxillofac Surg 1984;42(3):143. PubMed
34. Misiek DJ, Kent JN, Carr RF. Soft tissue responses to hydroxylapatite particles of different shapes. J Oral Maxillofac Surg 1984;42(3):150. PubMed
35. Shimizu SI. Subcutaneous tissue responses in rats to injection of fine particles of synthetic hydroxyapatite ceramic. Biomed Res. 1988; 9: 95-111
36. Mayer R, Lightfoot M, Jung I. Preliminary evaluation of calcium hydroxylapatite as a transurethral bulking agent for stress urinary incontinence. Urology 2001;57(3):434. PubMed
37. Stein J, Eliachar I, Myles J, et al. Histopathologic study of alternative substances for vocal fold medialization. Ann Otol Rhinol Laryngol 2000;109(2):221. PubMed
38. Pettis GY, Kaban LB, Glowacki J. Tissue response to composite ceramic hydroxyapatite/demineralized bone implants. J Oral Maxillofac Surg 1990;48(10):1068. PubMed
39. Radiance Package Insert. Franksville, WI: http://www.bioforminc.com/US/physiciantRegulatory-Status.htm.; 2004 2004.
40. Sklar JA, White SM. Radiance FN™: a new soft tissue filler. Dermatol Surg 2004;30(5):764. PubMed
41. Tzikas TL. Evaluation of the Radiance FN™ Soft Tissue Filler for Facial Soft Tissue Augmentation. Arch Facial Plast Surg 2004;6(4):234. PubMed
42. Hobar PC, Pantaloni M, Byrd HS. Porous hydroxyapatite granules for alloplastic enhancement of the facial region. Clin Plast Surg 2000;27(4):557. PubMed
43. Costantino PD, Friedman CD, Jones K, et al. Hydroxyapatite cement. II. Basic chemistry and histologic properties. Arch Otolaryngol Head Neck Surg 1991;117(4):379. PubMed
44. Havlik RJ. Hydroxyapatite. Plast Reconstr Surg 2002;110(4):1176. PubMed
45. James J, Carruthers A, Carruthers J. HIV-associated facial lipoatrophy. Dermatol Surg 2002;28(11):979. PubMed
46. Grunfeld C, Tien P. Difficulties in understanding the metabolic complications of acquired immune deficiency syndrome. Clin Infect Dis 2003;37 Suppl 2:S43. PubMed
47. Barbaro G. HIV-associated lipodystrophy: pathogenesis and clinical features. Adv Cardiol 2003;40:97. PubMed
48. Carr A. HIV lipodystrophy: risk factors, pathogenesis, diagnosis and management. Aids 2003;17 Suppl 1:S141. PubMed
49. Power R, Tate HL, McGill SM, et al. A qualitative study of the psychosocial implications of lipodystrophy syndrome on HIV positive individuals. Sex Transm Infect 2003;79(2):137. PubMed
50. Miller V, Sabin C, Hertogs K, et al. Virological and immunological effects of treatment interruptions in HIV-1 infected patients with treatment failure. Aids 2000;14(18):2857. PubMed
51. Carr A, Samaras K, Chisholm DJ, et al. Pathogenesis of HIV-1-protease inhibitor-associated peripheral lipodystrophy, hyperlipidaemia, and insulin resistance. Lancet 1998;351(9119):1881. PubMed
52. Mallal SA, John M, Moore CB, et al. Contribution of nucleoside analogue reverse transcriptase inhibitors to subcutaneous fat wasting in patients with HIV infection. Aids 2000;14(10):1309. PubMed
53. Miyazaki Y, Glass L, Triplitt C, et al. Effect of rosiglitazone on glucose and non-esterified fatty acid metabolism in Type II diabetic patients. Diabetologia 2001;44(12):2210. PubMed
54. Mayerson AB, Hundal RS, Dufour S, et al. The effects of rosiglitazone on insulin sensitivity, lipolysis, and hepatic and skeletal muscle triglyceride content in patients with type 2 diabetes. Diabetes 2002;51(3):797. PubMed
55. Sutinen J, Kannisto K, Korsheninnikova E, et al. Effects of rosiglitazone on gene expression in subcutaneous adipose tissue in highly active antiretroviral therapy-associated lipodystrophy. Am J Physiol Endocrinol Metab 2004;286(6):E941. PubMed
56. Martinez E, Conget I, Lozano L, et al. Reversion of metabolic abnormalities after switching from HIV-1 protease inhibitors to nevirapine. Aids 1999;13(7):805. PubMed
57. Moyle GJ, Baldwin C, Langroudi B, et al. A 48-week, randomized, open-label comparison of three abacavir-based substitution approaches in the management of dyslipidemia and peripheral lipoatrophy. J Acquir Immune Defic Syndr 2003;33(1):22. PubMed
58. McComsey GA, Ward DJ, Hessenthaler SM, et al. Improvement in lipoatrophy associated with highly active antiretroviral therapy in human immunodeficiency virus-infected patients switched from stavudine to abacavir or zidovudine: the results of the TARHEEL study. Clin Infect Dis 2004;38(2):263. PubMed
59. Martinez E, Arnaiz JA, Podzamczer D, et al. Substitution of nevirapine, efavirenz, or abacavir for protease inhibitors in patients with human immunodeficiency virus infection. N Engl J Med 2003;349(11):1036. PubMed
60. Carr A, Hudson J, Chuah J, et al. HIV protease inhibitor substitution in patients with lipodystrophy: a randomized, controlled, open-label, multicentre study. Aids 2001;15(14):1811. PubMed
61. Faure M. [Complications from silicone implants and other so-called inert materials]. Ann Dermatol Venereol 1995;122(6-7):455. PubMed
62. Pimentel L, Barnadas M, Vidal D, et al. Simultaneous presentation of silicone and silica granuloma: a case report. Dermatology 2002;205(2):162. PubMed
63. Milojevic B. Complications after silicone injection therapy in aesthetic plastic surgery. Aesthetic Plast Surg 1982;6(4):203. PubMed
64. Wilkie TF. Late development of granuloma after liquid silicone injections. Plast Reconstr Surg 1977;60(2):179. PubMed
65. Rapaport MJ, Vinnik C, Zarem H. Injectable silicone: cause of facial nodules, cellulitis, ulceration, and migration. Aesthetic Plast Surg 1996;20(3):267. PubMed
66. Amemiya T, Dake Y. Granuloma after augmentation of the eyelids with liquid silicone: an electron microscopic study. Ophthal Plast Reconstr Surg 1994;10(1):51. PubMed
67. Ficarra G, Mosqueda-Taylor A, Carlos R. Silicone granuloma of the facial tissues: a report of seven cases. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2002;94(1):65. PubMed
68. Ritt MJ, Hillebrand-Haverkort ME, ten Veen JH. Local treatment of facial lipodystrophy in patients receiving HIV protease inhibitor therapy. Acta Chir Plast 2001;43(2):54. PubMed
69. Friedman PM, Mafong EA, Kauvar AN, et al. Safety data of injectable nonanimal stabilized hyaluronic acid gel for soft tissue augmentation. Dermatol Surg 2002;28(6):491. PubMed
70. Olenius M. The first clinical study using a new biodegradable implant for the treatment of lips, wrinkles, and folds. Aesthetic Plast Surg 1998;22(2):97. PubMed
71. Duranti F, Salti G, Bovani B, et al. Injectable hyaluronic acid gel for soft tissue augmentation. A clinical and histological study. Dermatol Surg 1998;24(12):1317. PubMed
72. Lupton JR, Alster TS. Cutaneous hypersensitivity reaction to injectable hyaluronic acid gel. Dermatol Surg 2000;26(2):135. PubMed
73. Shafir R, Amir A, Gur E. Long-term complications of facial injections with Restylane (injectable hyaluronic acid). Plast Reconstr Surg 2000;106(5):1215. PubMed
74. Raulin C, Greve B, Hartschuh W, Soegding K. Exudative granulomatous reaction to hyaluronic acid (Hylaform). Contact Dermatitis. 2000 Sep;43(3):178-9. PubMed
75. Fernandez-Acenero MJ, Zamora E, Borbujo J. Granulomatous foreign body reaction against hyaluronic acid: report of a case after lip augmentation. Dermatol Surg. 2003 Dec;29(12):1225-6. PubMed
76. Schanz S, Schippert W, Ulmer A, Rassner G, Fierlbeck G. Arterial embolization caused by injection of hyaluronic acid (Restylane Br J Dermatol. 2002 May;146(5):928-9 PubMed
77. Narins RS, Brandt F, Leyden J, Lorenc ZP, Rubin M, Smith S. A Randomized, Double-Blind, Multicenter Comparison of the Efficacy and Tolerability of Restylane Versus Zyplast for the Correction of Nasolabial Folds. Dermatol Surg. 2003 Jun;29(6):588-95. PubMed
78. Tzikas TL. Radiance patient satisfaction. Dermatology Times 2003 July;62.
79. Klein A. Commentary. Dermatological Surgery 2004;30(5):768. PubMed
© 2004 Dermatology Online Journal