64.1 Introduction

Lipodystrophy (LD), referring to morphologic changes and metabolic alterations, affecting HIV-1-infected patients, was first described in 1998 [1–5]. The main clinical features are peripheral fat loss or lipoatrophy of the face, limbs, and buttocks and central fat accumulation within the abdomen, breast, and the dorsocervical spine both of which may be present in the same individual [6, 7].

Facial lipoatrophy, in particular, includes loss of the buccal fat and temporal fat pads and leads to facial skeletonization with concave cheeks, prominent nasolabial folds, periorbital hollowing, and visible facial musculature [8–10]. This volume deficit alters the contour of the face from youthful, healthy, convex curves to aged, pathologic, concave contours [11–14]. The net aesthetic result is of an accelerated aging process of the face appearance.

It is intuitive that facial lipoatrophy is the most stigmatizing feature of HIV-related LD, as face cannot be

G. Guaraldi ( )

Department of Medicine and Medicine Specialities, Infectious Diseases Clinic, University of Modena and Reggio Emilia School of Medicine,

Via del Pozzo 71, 41100, Modena, Italy e-mail: giovanni.guaraldi@unimore.it

P.L. Bonucci

Chirurgia plastica, Salus Hospital, Reggio Emilia, Italy and Hesperia Hospital Modena, Modena, Italy e-mail: pierluigibonucci@virgilio.it

D. De Fazio

Chirurgia plastica, Salus Hospital, Reggio Emilia, Italy and casa di cura: S. Pio X, Milano, Italy e-mail: dododefazio@libero.it

masked by clothes and usually it is perceived as the manifestation of our health. Many studies have demonstrated that LD causes negative psychosocial impact and an impairment of quality of life because of erosion of self-image and self-esteem, demoralization and depression, problems in social and sexual relations, and threats to locus of control. Often LD forces HIV disclosure [15].

Surgical treatments for facial lipoatrophy include autologous fat transplant (AFT) from a subcutaneous abdominal graft or injections of biodegradable or nonbiodegradable fillers into the lipoatrophic areas of the face.

64.2 Comparative Studies

It is surprising how very few studies have assessed safety, efficacy, and durability of these interventions and only two partially randomized studies have compared different surgical approaches [16, 17].

The first partially randomized study was conducted at the Metabolic Clinic of the University of Modena and Reggio Emilia, where an extensive surgery experience for HIV-related facial lipoatrophy has been gathered from 2001. Eligible individuals with enough residual subcutaneous fat were offered to receive AFT; the others were blindly assigned to two different surgical teams who administered a set of PLA or PAAG injections every 4 weeks. The primary endpoint was the measurement of Bichat’s fat pad region determined by the result of dermal plus subcutaneous thickness. Secondary endpoints included body image evaluation (ABCD questionnaire), facial aesthetic satisfaction (Visual Analogue Scale), and aesthetic pre and

postpicture comparisons by independent reviewers. All variables were measured at baseline and week 24.

Twenty-four individuals received AFT and 35 were selectively randomized to PLA [18] or PAAG [15] infiltrations. PLA and PAAG groups received a mean of five to six injections, respectively (p = ns). The mean change in fat thickness was respectively 3.3 ± 4.1; 3.5 ± 4.0; 2.1 ± 3.0 mm (p = .687). The mean change in ABCD score result was poorer in the AFT arm but there were no other differences in other measured parameters. Four serious adverse events were documented in the AFT arm represented by facial fat graft hypertrophy, which occurred at the beginning of the authors’ clinical experience when areas of fat hypertrophy (mainly buffalo hump) were used for graft site. These subjects developed facial fat hypertrophy at the same time of recurrence of fat hypertrophy in the harvest site. Patients described themselves as “hamster” because of the swollen cheeks, and this clinical picture has been published as “Hamster syndrome” [16]. This phenomenon is no more observed since the use of fat hypertrophy for harvest site is avoided. All three interventional techniques were highly effective in improving the aesthetic satisfaction of the patients. Figure 64.1 represents three cases from this series in which an equal satisfactory aesthetic result was obtained. Physical examination does not allow the identification of which surgical procedure was performed in each case.

The second study by Negredo et al., evaluated the clinical efficacy of facial infiltrations with autologous

fat, polylactic acid, and polyacrylamide gel using clinical inspection and facial photographs as well as patient satisfaction, emotional status, and quality of life. Evaluations were made at 48-week follow-up. Analysis included 138 patients: 8, 25, and 105 in the fat, polylactic acid, and polyacrylamide gel groups, respectively. At baseline, almost 50% of the patients (67/138) presented grades 3 and 4 lipoatrophy, but at week 48 only 7.5% (7/93) remained in these advanced grades (no patients from the polyacrylamide group). A new round of infiltrations at week 48 was necessary in 35% (33/93) of patients (88%, 84%, and 8% in the fat, polylactic, and polyacrylamide groups, respectively). No serious adverse events were detected with any of the substances. Patient satisfaction and quality of life improved significantly in all three groups. Infiltrations with autologous fat, polylactic acid, or polyacrylamide gel have appeared to be an effective and safe alternative to repair facial lipoatrophy, at least up to 48 weeks, significantly improving patient quality of life. Similar results were observed for all degrees of severity and between genders. Polyacrylamide gel provided the lon- gest-lasting benefits.

Establishing endpoints is challenging for comparative studies of facial fillers that work by different mechanisms. Assessment by photographs may not lead to reproducible results and is operator-dependent, and the continuation of specific antiretroviral therapies may also influence outcomes. Fortunately, some attempts at comparison have been made, and funding for additional comparative data is being sought.

a

Fig. 64.3 (a) Preoperative. (b) After injection of 12 ml of PAAG (polyacrylamide gel) injected into each cheek

b

b

Some studies have utilized pictures comparisons and ultrasound assessment of cheek thickness as aesthetic outcomes. As previously said, it is necessary to consider PRO such as the assessment of BI, aesthetic perception, depression, and QoL. Long-term psychometric outcomes of plastic surgery for treatment of facial lipoatrophy have been described by Orlando et al. [19] in an observational, prospective, nonrandomized study of 299 participants (70.8% male). Fifty-four (18.1%) have undergone lipofilling (Fig. 64.1), 24 (8%) after an initial lipofilling have needed polylactic acid injections to correct cheek asymmetry, 91 (30.4%) have received only polylactic acid infiltrations (Fig. 64.2),

130 (43.5%) only polyacrylamide infiltrations (Fig. 64.3). At 48 weeks after end of surgery participants have shown an improvement of face satisfaction (by a Visual Analogue Scale from 2.9 ± 2.1 to 6.2 ± 2.1 (p < .0001), of body image satisfaction (ABCD question 7 from 3.8 ± 1 to 3.1 ± 1 p < .0001 and ABCD question 8 from 70.7 ± 16.7 to 77.2 ± 17.2 p < .0001), as well as improvement of objective outcome as the augmentation of both cheeks thickness (right cheek from 4.3 ± 1.9 to 9.5 ± 3 mm p < .0001, left cheek from 4.4 ± 2 to 9.6 ± 3.1 mm, p < .0001). Notwithstanding surgery has been limited to the face; all patients have reported body image improvement even though the ABCD

questionnaire had no specific questions or items referring to facial lipoatrophy. Apparently facial surgery has resulted in an improvement of whole body aesthetic satisfaction and psycho-social life (social and sexual life, health perception, habits, affections, relationships). This positive effect was evident in the overall sample and in the polylactic acid and polyacrylamide groups, while it has reached no statistical significance in the lipofilling group. One of the most striking impacts of surgery was on depression as assessed by the Beck depression inventory (BDI) [20]. This is a self-administered 21 item scale measuring supposed manifestations of depression. It includes factors reflecting negative attitudes towards self, performance impairment and somatic disturbances, as well as a general factor of depression [18]. The BDI takes approximately 10 min to complete. The higher the score, the greater the state of depression. Total possible score ranges from 0 to 63. Mild depression was defined as a value between 9 and 17, a moderate depression between 18 and 29, and a severe depression for values greater than 30. At follow-up, the change in BDI revealed a significant improvement in the depression score for the overall cohort from 11.4 ± 8.3 (corresponding to mild depression) to 9.4 ± 7.8 (almost absence of depression), p = 0.001. Nevertheless, analyzing the score by single surgery group the change was significant in the polylactic acid and polyacrylamide groups only (lipofilling score changed from 10 ± 8.3 to 10.4 ± 8.7, p = ns; lipofilling + polylactic acid score changed from 15.6 + 10.5 to 12.7 + 12.1, p = ns; polylactic acid score changed from 10.7 ± 7.4 to 8 ± 6.5, p = 0.001; polyacrylamide score changed from 11.8 ± 8.5 to 9.6 ± 8.1, p = 0.014).

Table 64.1 summarizes the studies that have assessed safety, efficacy, and durability of different surgical interventions for treatment of facial lipoatropy.

64.3How to Choose Different Surgical Procedures to Treat HIV-Related Facial Lipoatrophy

The most important prerequisite to the choice is the expertise of the health care worker; thus plastic reconstructive surgeons should always be the preferred ones, and are needed to perform autologous fat transplant. Given the excellent aesthetic result of lipofilling and both biodegradable and nonbiodegradable fillers the choice of the best surgical procedure is not a matter of aesthetic issues. Generally speaking biodegradable fillers should be the first choice in younger people in order to allow a better adaptation of the filler with the physiological aging process, unless grade 4 facial lipoatrophy where high volume injection is needed. This result, indeed, can be obtained mainly with autologous fat transplant, when feasible, or with nonbiodegradable fillers. In case of patients often suffering from sinusitis or dental granuloma or undergoing odonto-stomato- logic procedure, nonbiodegradable fillers should be avoided because of the risk of local infection or granuloma that may potentially occur years after the filling procedure as long-term complications. Short-term complications, mainly represented by local edema, infection, and bleeding are few when filler are injected with small-gauge needle, and always self-limiting, but

Negredo, AIDS

Patient Care

STDS, 2006 [17]