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716

L. Nelson and K.J. Stewart

63.18 Discussion

The degree of resorption of autologous fat grafts remains a topic of debate and is mainly based on subjective observation of surgically treated areas over time. Indeed, studies are difficult to compare due to the wide variability in technique, experience of the surgeon and means of evaluating outcome. Compared to other non-permanent fillers, the longevity of autologous fat is not as easily predictable. For patients with HIV lipodsytrophy, the unpredictable nature of the technique is even more apparent due to the underlying systemic lipodystrophic process. Quantification of surgical outcome in HIV-infected patients undergoing autologous fat transfer for facial lipoatrophy is lacking, and studies are limited by small numbers, subjective assessment and lack of long-term data.

In one study, 38 patients received autologous fat injections using the Coleman technique for HIV facial lipoatrophy [31]. The cosmetic result was evaluated at 6 months, after which 12 patients required a new injection of fat to improve symmetry and resorption. At 1 year, the cosmetic result was rated as good to excellent by the patient, the clinic nurse and the surgeon. Less resorption was reported in cases where the fat was not centrifuged and the authors suggest that this may be due to decreased trauma to the fat. In another study, the outcome of the Coleman technique was evaluated in 33 HIV-infected patients by clinical examination, biochemical data, patient satisfaction and standardised photographs at baseline and 1 year following lipostructure [70]. Improvement was found in 12 patients by 3 independent evaluators at 12 months and 93% of patients were satisfied with the results. The authors also report that quantity of fat injected and low serum triglyceride level before surgery were significantly associated with improvement of facial lipoatrophy.

Similar outcome measures were evaluated in two further studies to demonstrate the efficacy of lipostructure in HIV-infected patients using the Coleman technique for facial lipoatrophy. Levan et al. reported 93% patient satisfaction and ‘acceptable’, ‘good’ or ‘very good’ results in 13 out of 14 patients evaluated by a 5-member jury 6 months following the procedure [71]. Caye et al. evaluated 29 HIV-infected patients treated using the Coleman technique and reports durability of fat grafts at 6 months based on serial photography [72]. The results were deemed good in 72.4%, acceptable in 13.8% and poor in 13.8%. Davison et al. have utilised lipoaspirate in patients undergoing suction-assisted

liposuction for buffalo hump deformities to correct associated facial wasting [73]. In these cases, the fat grafts were not centrifuged to avoid aerosolisation of the virus. The authors report graft take of approximately 40–50% based on subjective assessment, and postulate that fat harvested from dystrophic sites possesses different biochemical properties from nonhypertrophic fat and may lead to more sustained results in these patients.

However, Talmor et al. feel that the quality of fat rendered from dystrophic sites makes it unsuitable for transfer due to its extremely fibrous nature [8]. Also, the potential for fat graft hypertrophy when utilised from dystrophic sites should be considered. Since HIV lipodystrophy is a systemic, metabolic disease, the effect of transferring dystrophic fat can be unpredictable. In one study of 41 patients who received autologous fat injections for HIV-associated lipoatrophy, 4 patients developed disfiguring facial lipohypertrophy at the injection site [74]. The fat source was the dorsocervical fat pad in three of these patients. The pathogenic mechanism for this is unknown. The authors hypothesise that the mechanism may be related to adipocyte receptors and mitochondrial toxicity: receptor expression could be transferred from the harvest site and remain sensitive to lipohypertrophy determinants. Another hypothesis is that lipohypertrophy of the cheeks may be the result of expansion of brown fat that is transferred with the intervention. Histological examination of hypertrophied fat graft to the nasogenian area was carried out following surgical resection in one patient. Fibroadipose tissue and dystrophic adipocytes of various sizes were demonstrated. The authors postulate that a non-adaptive response could be partly related to dysfunction of adipocyte receptor expression and a mutated DNA toxicity-related mechanism.

The perceived success of autologous fat transfer depends on whether one considers long-term resorption disappointing or potentially superior to the anticipated longevity of other non-permanent fillers. Multiple treatments with autologous fat transfer may be required in patients with severe facial lipoatrophy to achieve volume augmentation (Fig. 63.8). Paucity of subcutaneous donor fat is another limitation of the technique in patients with generalised lipoatrophy and synthetic injectable fillers may be an alternative treatment option. The use of various facial fillers has been reported in the treatment of HIV facial lipoatrophy. Eviatar et al. have evaluated the safety and efficacy of calcium hydroxyapatite (Radiesse®) in 100 patients

63 Autologous Fat Transfer for HIV-Associated Facial Lipodystrophy

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Fig. 63.8 Multiple treatments with autologous fat transfer may be required in patients with severe facial lipoatrophy to achieve volume augmentation. (a) Pre-operative. (b) Postoperative 4 months following first fat transfer. (c) Ten months following second fat transfer

a

b

c

with HIV-associated facial lipoatrophy [75]. Eightyfive percent of patients received touch-up injections at 1 month following initial treatment. The study demonstrated that all patients had improved aesthetic outcomes at 6 months as scored on a facial global aesthetic improvement rating scale. The use of hyaluronic acid has been evaluated for soft-tissue augmentation of HIV-associated facial lipodystrophy in five patients [76]. Each patient received approximately 5–6 ml in total of hyaluronic acid in the malar

area via intradermal injection. The technique was found to provide a good cosmetic result for at least 6 months, with high patient satisfaction and no adverse events. Another study of seven patients with HIVassociated facial lipodystrophy treated with hyaluronic acid revealed high patient satisfaction with regard to cosmetic improvement, and no side effects of treatment [77].

The VEGA study evaluated the safety and efficacy of Poly-L-lactic acid injections (New-fill) in 50 patients

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with HIV-associated lipoatrophy by means of an openlabel, single-arm, pilot study [78]. The authors report a significant increase in dermal thickness from baseline, as assessed by facial ultrasound, for a duration of 96 weeks post treatment. There were no serious adverse events although in 44% of patients, palpable but nonvisible subcutaneous nodules developed. Similar results were found by Moyle et al. who report a mean increase in dermal thickness of 4–5 mm within 12 weeks of treatment with effects persisting at least 18 weeks beyond the last injection [79].

There have been reports on the use of liquid injectable silicone in patients with HIV-associated facial lipoatrophy including a case report of 1 patient [80] and larger study of 77 patients [81]. Facial contours were restored and significant patient satisfaction was achieved with no adverse events noted. Both papers conclude that silicone oil is a safe and effective treatment for HIV-associated facial lipoatrophy. However, longer-term safety and efficacy in HIV patients remains unproven.

Several studies have reported stability, tolerance and safety of Bio-Alcamid® with permanent, satisfactory improvement in appearance for patients with lipodystrophy [82–84]. In one study, 90% of the 73 patients required a second injection of Bio-Alcamid® (4 weeks after the first injection) to improve implant appearance [84]. The aesthetic results were deemed excellent by both physicians and patients at follow-up of 3 years. However, the long-term results of Bio-Alcamid® are uncertain and complications such as infection, capsular contraction and migration have been reported, necessitating removal of the product [85].

Thus, the less predicable long-term volume augmentation achievable with autologous fat must be balanced against the risks of allergic responses and other complications relating to synthetic injectable fillers. The simplicity and safety of autologous fat transfer also makes it an attractive option compared to other surgical options for HIV facial lipoatrophy including the use of dermis-fat grafts, flaps and implants.

Peer advocated the use of free fat grafts with overlying dermis for patients with soft-tissue defects in 1956. The results of dermis-fat graft transfer to the malar area in patients with HIV-associated lipodystrophy have been variable. Strauch et al. evaluated this technique in five patients (four female and one male) with HIV-associated facial lipodystrophy [86]. Dermisfat grafts were transferred from the abdominal wall to

malar pockets through a trans-oral approach. Patients were overcorrected to twice the expected final volume and they reached final volume (50% of initial augmentation) in 3–5 months. The aesthetic results were maintained during the follow-up period of 14–30 months. However, others reporting on the use of a dermis-fat graft to treat HIV-associated lipodystrophy have been sceptical about the technique as a consequence of patient dissatisfaction and surgical complications [87]. The donor site scars may also be unacceptable. Breast tissue from gynaecomastia resection has also been reported in HIV patients and has minimal donor site scar although the small risk of potential carcinomatous change is a drawback.

With the advent of microvascular surgery and free flap transfer, numerous flaps have been used to treat patients with lipodystrophy including a double paddle dermis-fat forearm free flap [88], adipofascial free radial forearm flap [89] and a temporalis muscle rotation flap [90]. However, potential disadvantages with free tissue transfer include multiple procedures, lengthy operation, flap failure, hematoma and donor site defects [89, 91].

The use of submalar silicone implants has been evaluated in patients with HIV-associated lipodystrophy. In one study, three patients with facial lipoatrophy underwent reconstruction with submalar silicone implants via an intra-oral approach [8]. No infection or extrusion was encountered, although one patient required implant repositioning on one side. At 15 months follow-up, both patients and surgeons were satisfied with the results. However, the decreased immunity inherent to the HIV-positive surgical patient and the risk of peri-implant infection represents a significant concern. Indeed, reports of infection and erosion of the implant through the anterior maxilla have been published [92, 93].

63.19 Conclusions

The treatment of HIV-associated lipodystrophy remains a challenging problem for physicians. The wide choice of treatment options and problems inherent to HIVinfected individuals can make management decisions difficult. In general, autologous fat transfer is an effective treatment due to the biocompatibility, safety and satisfactory aesthetic results of this technique. However,

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paucity of donor and unpredictable resorption rates are the main drawbacks in the treatment of patients with HIV-associated lipodystrophy, and the use of synthetic fillers or alternative surgical techniques may be considered. Further studies using objective measures are required to quantify the long-term outcome of autologous fat grafting, particularly in patients with HIVassociated lipodystrophy, who may respond differently from non-lipodystrophic patients.

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