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Gluteal Augmentation in Patients with Lipodystrophy Due to the Use of Antiretroviral Therapy
Abstract
With the introduction of effective antiretroviral therapy for the treatment of human immunodeficiency virus infection in 1996, there has been a surge of patients with body contour abnormalities that present with central fat accumulation and peripheral fat loss. Fortunately, there are many surgical approaches to help patients with these deformities. Loss of volume and projection, hip narrowing, widening of the intergluteal cleft, persistent dermatitis and ulcers characterize the gluteal deformities seen in these patients. A classification of gluteal lipoatrophy is presented in this chapter in order to adequately manage these patients. Silicone implants, autologous fat grafting and polymethyl methacrylate injections are among the most common procedures performed for these patients. There are several benefits for treating HIV-associated lipodystrophy beyond pure aesthetics. Changes in body morphology can be associated with psychological stress that can affect patients’ self-esteem and adherence to the medications. Therefore, plastic surgery procedures are highly indicated for patients presenting lipodystrophy caused by antiretroviral therapy.
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Introduction
The shape and size of the buttocks are essential to the notion of bodily beauty. This has resulted in a growing interest in gluteoplasty among both women and men. The aim of the present study was to present the author’s experience with gluteoplasty using the intramuscular XYZ method.
Method
Between 2010 and 2015, 29 patients aged 22 to 64 years (average, 43 years) underwent gluteoplasty; of these 26 were women (89.66%) and 3 were men (10.34%). Round or oval implants were used, with volumes of 240 to 420 ml (average, 330 ml), depending on the individual case.
Results
Good results were obtained in terms of volume increase and harmony of the gluteal region, with a high degree of patient satisfaction.
Conclusions
The intramuscular XYZ method was safe, both for primary and secondary surgery, to treat cases of asymmetry and/or visible implants. Predetermining the XYZ reference points makes this procedure safe and reproducible.
Keywords:
Reconstructive surgical procedures; Buttocks; Silicone elastomers; Prosthesis and implants
Introduction
Since the introduction of highly active antiretroviral therapy for the treatment of human immunodeficiency virus (HIV), disease mortality has been dramatically reduced worldwide. One related side effect from the use of these drugs is gluteal lipodystrophy. The aim of this study is to assess the quality-of-life impact of correcting this deformity in HIV patients.
Methods
A historical cohort study was conducted between January 2010 and December 2014 with 23 patients, assessing the quality of their lives using the Nottingham Health Profile. A statistical analysis was performed using the McNemar test for related samples.
Results
There was a significant difference between preoperative and postoperative response in 19 of the 38 questions.
Conclusion
We may say that gluteal reconstruction plays a role in improving quality of life for HIV patients who have been affected by antiretroviral related gluteal lipodystrophy.
Keywords:
Buttocks; HIV-associated lipodystrophy syndrome; Quality of life
Progression of lipodystrophy syndrome is a big challenge in HIV treatment. Nowadays, fat loss at the lower part of buttocks has become another problem as patients have started to complain that it is painful to be seated for a long time and/or on hard surfaces. We developed a method for buttock lipoatrophy treatment with PMMA-microspheres, as silicone prostheses and autologous fat transplant were not completely efficient. The treatment consisted of net-crossed injections, in the subcutaneous layer, of a 30% PMMA-microspheres solution on the atrophic areas of the buttock. One hundred and fifty-four patients were included. The amount of PMMA-microspheres used to treat buttock lipoatrophy depended on the degree of atrophy and size of the area to be treated. Patients were satisfied with this treatment and reported to be more comfortable to be seated for longer period of time. We demonstrated that soft tissue augmentation with PMMA-microspheres is safe and efficient for the treatment of buttock lipoatrophy associated with HIV lipodystrophy.
Long-term use of both zidovudine (AZT) and stavudine (d4T) is associated with lipoatrophy, but it occurs possibly through different mechanisms.
Surgical biopsy specimens of subcutaneous adipose tissue were obtained from 18 human immunodeficiency virus type 1 (HIV-1)-infected lipoatrophic patients (the LA+ group) who were treated with either zidovudine (the AZT+LA+ group; n = 10) or stavudine (the d4T+LA+ group; n = 8) and from 10 nonlipoatrophic HIV-1-infected patients (the LA- group) who received antiretroviral therapy. Mitochondrial DNA (mtDNA) copy numbers, gene expression, and immunohistochemistry data were analyzed.
mtDNA copy numbers were significantly reduced in the LA+ group, compared with the LA- group, and in the d4T+LA+ group, compared with the AZT+LA+ group. The ratio of mtDNA-encoded cytochrome COX3 to nuclear DNA-encoded COX4 expression was significantly lower in the LA+ group than in the LA- group. Compared with the LA- group, the LA+ group had significantly lower expression of genes involved in adipogenesis (SREBP1c and CEBPB), lipid (fatty acid synthase), and glucose (GLUT4) metabolism. Expression of genes involved in mitochondrial biogenesis (PGC1B), apoptosis (FAS), inflammation (IL1B), oxidative stress (PCNA and SOD1), and lamin B was significantly higher in the LA+ group than in the LA- group. The d4T+LA+ group had significantly lower expression of genes involved in mitochondrial biogenesis (POLG1), energy metabolism (the COX3/COX4 ratio), adipogenesis (SREBP1c and CEBPA), perilipin, and hexokinase than did the AZT+LA+ group. There were 7-fold more macrophages in adipose tissue specimens obtained from patients in the LA+ group, compared with the LA- group.
Lipoatrophy is characterized by mtDNA depletion, inflammation, and signs of apoptosis. Changes were more profound in the d4T+LA+ group than in the AZT+LA+ group.
Inhibitors of HIV-1 protease produce a rapid decrease in plasma HIV-1 RNA, with concomitant immune reconstitution. However, severe metabolic side effects together with a previously unseen form of lipodystrophy have been associated with long-term use of protease-inhibitor therapy. The pathogenic mechanisms underlying HIV-1 protease inhibitor-associated lipodystrophy are still largely unknown.
Fourteen HIV-infected patients with HIV-1 protease inhibitor-associated lipodystrophy had a biopsy of subcutaneous fat performed in the antero-lateral aspect of the right leg. The samples were submitted for standard pathologic study together with a careful search for adipocyte apoptosis. Apoptosis was assessed by the terminal deoxynucleotidyl transferase dUTP-digoxigenin nick end labelling (TUNEL) method, using the ApopTag kit (Oncor, Gaithersburg, Maryland, USA). The procedure was performed between three and five times for each sample. Appropriate positive and negative controls were used. Controls which were subcutaneous fat biopsies from patients with untreated melanoma were also examined for the presence of apoptosis.
Fourteen HIV-infected patients with a mean exposure to HIV-1 protease inhibitors of 12.6 +/- 3.7 months (range: 6-21 months), developed the characteristic features of HIV-1 protease inhibitor-associated lipodystrophy. All but one patient had an abnormal waist:hip ratio, and they all exhibited an abnormal serum lipid profile. Pathologically, subcutaneous fat atrophy was a constant feature, along with focal lipogranuloma formation and vascular proliferation. One of the eleven assessable biopsy samples was negative for the presence of apoptosis, six showed focally positive apoptotic cells, and the remaining four biopsies demonstrated moderate positivity. Apoptotic changes were also detected in endothelial cells. Apoptotic changes were more pronounced in patients with higher increases in CD4 and CD8 counts, and in those with a greater decay in plasma viral load.
Subcutaneous adipocyte apoptosis occurs in lipoatrophic areas of patients with HIV-1 protease inhibitor-associated lipodystrophy.
Peripheral lipoatrophy may complicate antiretroviral therapy of human immunodeficiency virus (HIV) infection, often related to duration and type of nucleoside analog therapy, and may have a mitochondrial pathogenesis. No proven therapy exists for lipoatrophy, but abacavir is a nucleoside analog that may be less toxic to mitochondria.
To determine if substitution of stavudine or zidovudine with abacavir improves HIV lipoatrophy without affecting control of HIV replication.
Randomized, open-label 24-week study.
Seventeen hospital HIV outpatient clinics and primary care centers in Australia and England, with randomization from June 2000 through January 2001.
A total of 111 adults (109 men) with moderate or severe lipoatrophy who were receiving stavudine (n = 85) or zidovudine (n = 26) and had stable plasma HIV RNA levels below 400 copies/mL and no prior abacavir therapy.
Patients were randomly assigned to switch from stavudine or zidovudine to abacavir, 300 mg twice per day, while continuing all other antiretroviral therapy (n = 54) or to continue all antiretroviral therapy (n = 57).
The primary end point was limb fat mass, measured by dual-energy x-ray absorptiometry; key secondary end points were plasma HIV RNA levels, adverse events, physician-assessed (via subjective measures) lipodystrophy severity, total and central fat mass, and fasting metabolic (lipid, glycemic, and lactate) levels.
There was a significant increase in limb fat in the abacavir group relative to the stavudine/zidovudine group (0.39 vs 0.08 kg; mean difference, 0.31; 95% confidence interval [CI], 0.06-0.57 kg), as well as significant relative increases in subcutaneous thigh (P =.01), arm (P<.001), and abdominal (P =.001) fat areas on computed tomography. Switching had no significant effect on secondary end points, including plasma HIV RNA (for unadjusted comparison between groups at week 24, odds ratio, 1.38; 95% CI, 0.48-3.96). Change in limb fat mass at week 24 did not correlate with change in subjectively determined perceived lipoatrophy severity (r = -0.06; P =.53 by Spearman correlation). Hypersensitivity to abacavir was seen in 5 patients (10%).
In this sample of lipoatrophic HIV-infected adults, switching from stavudine or zidovudine to abacavir for 24 weeks led to significant, albeit modest, objectively measured increases in limb fat. Clinical lipoatrophy, as assessed subjectively, did not resolve, however, and at the rate of increase observed may take years to resolve with use of this strategy. Longer-term follow-up is needed.
Alterations in serum lipid values have been widely reported among persons infected with human immunodeficiency virus (HIV) type 1 treated with highly active antiretroviral therapy (HAART), but no data have yet been reported on changes from preseroconversion lipid values.
To describe changes in serum cholesterol levels associated with HIV infection and antiretroviral medication exposure, and 1-time assessment of triglyceride levels post-HAART initiation.
The Multicenter AIDS Cohort Study, a prospective study in which homosexual and bisexual men were enrolled and from which 50 of 517 HIV seroconverters were drawn for the analysis herein, who later initiated HAART, involving measurements of stored serum samples obtained between 1984 and 2002.
Changes in levels of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) at 6 time points during an average of 12 years; 1-time assessment of triglyceride levels from the third post-HAART clinic visit.
Among the 50 men, notable declines in mean serum TC (-30 mg/dL [-0.78 mmol/L]), HDL-C (-12 mg/dL [-0.31 mmol/L]), and LDL-C values (-22 mg/dL [-0.57 mmol/L]) were observed after HIV infection. Following HAART initiation, there were large increases in mean TC and LDL-C values (50 and 21 mg/dL [1.30 and 0.54 mmol/L], respectively); however, the mean changes from the preseroconversion values were 20 mg/dL (0.52 mmol/L) (95% confidence interval [CI], -1 to 41) and -1 mg/dL (-0.03 mmol/L) (95% CI, -25 to 22), respectively. Mean HDL-C remained below baseline levels throughout follow-up. The median value (interquartile range) of triglycerides was 225 mg/dL (2.54 mmol/L) (147-331 mg/dL).
Before treatment, HIV infection results in substantial decreases in serum TC, HDL-C, and LDL-C levels. Subsequent HAART initiation is associated with increases in TC and LDL-C but little change in HDL-C. Increases in TC and LDL-C observed after about 3 years of HAART possibly represent a return to preinfection serum lipid levels after accounting for expected age-related changes.
The antiretroviral therapy for patients with human immunodeficiency virus (HIV) causes lipodystrophy, or a change in the distribution of body. Treatment for the facial changes is well addressed and covered in the recent literature, but female patients also report changes in their buttocks and lower limbs. There is no treatment for the lower limb deformity, but plastic surgeons can do something for the buttock. The authors propose a classification for the deformities of these patients and a new solution to improve the contour of this area and to reduce the social impact of deformity on women with HIV. This consists of placing two silicone implants, in the buttock and on the hip, to give a rounder appearance. The authors think that hip implants may be indicated also for gender reassignment surgery and for women with masculine features.
Autologous fat grafting is widely used in breast surgery to refine and optimize aesthetic outcomes. Despite its widespread use, obtaining predictable, reliable, and consistent outcomes remains a significant challenge and is influenced by the technique used for procurement, processing, and placement of the fat. At present, there is no published consensus on the optimal technique. The purpose of this article is to review current techniques at each stage of fat grafting and provide tips on best practices based on the published literature as well as our extensive clinical experience.
HIV lipodystrophy is a heterogeneous syndrome, which has yet to be objectively defined, comprising peripheral lipoatrophy, central fat accumulation and lipomata, along with hyperlipidaemia, insulin resistance and lactic acidaemia. Both nucleoside analogues and protease inhibitors are involved, but there are also host factors that probably place some patients at greater risk. The pathogenesis is increasingly understood, with evidence of interference of several regulatory proteins such as sterol regulatory enhancer binding protein-1, the proteasome, mitochondrial DNA polymerase gamma and GLUT-4. Along with the issues of cosmesis and stigmatization, a principal clinical concern that arises with lipodystrophy is a possible increased risk of accelerated atherosclerosis. A variety of therapeutic interventions, designed to limit these risks, are under evaluation, but none is conclusively shown to be of value.
Life-expectancy increased in patients infected with HIV/AIDS with the advent of highly active antiretroviral therapy (ART). Facial lipoatrophy is a common complication in these patients, eventually leading to stigma, segregation and a negative impact in quality of life (QOL). We measured the impact of the treatment of facial lipoatrophy with polymethyl methacrylate (PMMA) in the QOL of patients with HIV/AIDS by using four questionnaires that address QOL. Forty consecutive patients on ART referred for facial lipoatrophy treatment were enrolled in this study. The first 20 were allocated to the intervention group and were treated with tissue augmentation with PMMA. The other 20 were allocated to the control group, which received treatment only after six months. At baseline, four questionnaires were applied to all patients in both groups and again after six months. The variation in scores within the control group for all domains of all four instruments was significantly better when compared with that within the control group. We detected improvement in the QOL of patients with HIV/AIDS and facial lipoatrophy when they were treated with PMMA.
Adipose tissue alterations (ATA), which are common among persons treated with highly active antiretroviral therapy (HAART), can have substantial psychologic repercussions, with a subsequent negative impact on the patient's quality of life and on HAART adherence. However, the cross-sectional nature of the studies precludes establishing the direction and causality of the relationship. The authors evaluated the longitudinal relationship between ATA and adherence to HAART. The analysis included all participants in the AdICoNA and the LipolCoNA substudies of the Italian Cohort Naive Antiretrovirals (ICoNA). Adherence was assessed using a 16-item self-administered questionnaire, which also included a question on self-perceived fat accumulation experienced during the past 4 weeks. ATA was diagnosed by physicians at enrollment and evaluated every 6 months thereafter. There were 207 patients, with a median age of 35 years; 73% were men; and 34% acquired HIV through injection drug use. At baseline, nonadherence was reported by 63% of participants, and ATA was self-perceived by 15% and clinically diagnosed in 25%. Using Cox regression analysis, patients with good adherence at baseline were more likely to develop ATA (RH = 2.58; 95% CI, 1.09-6.11) and developed it sooner. Self-perceived ATA at baseline was independently related to subsequent nonadherence (OR, 4.67; 95% CI, 1.01-22.4), but clinically diagnosed ATA was not (OR, 0.77; 95% CI, 0.37-1.61). Patients' adherence to HAART is a dynamic process that interacts with ATA. Better adherence is associated with a higher risk of subsequent occurrence of ATA, while patient-perceived onset of morphologic alterations can reduce adherence to antiretroviral therapy.
Gluteal implants offer a good way not only to correct hypoplasias, but also to remodel and give rounded shape to buttocks, achieving beauty and sensuality. However, until recently, only a few surgeons have used this procedure. An intramuscular introduction of the implants may be a good means of reaching this goal, but because the undermining is performed without direct view, difficulties may occur in obtaining a symmetric and safe plane, and this can lead to unpleasant results. This report presents an intramuscular method based on geometry, in which three points (X, Y, and Z) and a line (G) in the pelvis define the plane in which the dissection must be performed, allowing more precise and safe undermining. From 1986 to 2003, 746 patients underwent surgery using this technique, achieving good results. This technique has proved to be a safe and reproducible way of performing augmentation gluteoplasty.
Both peripheral fat loss and central fat gain have been reported in HIV infection. Which changes are specific to HIV were determined by comparison with control subjects and the associations among different adipose tissue depots were determined.
Cross-sectional analysis of HIV-positive and control men from the study of Fat Redistribution and Metabolic Change in HIV Infection. Lipoatrophy or lipohypertrophy was defined as concordance between participant report of change and examination. Regional adipose tissue volume was measured by magnetic resonance imaging (MRI).
HIV-positive men reported more fat loss than controls in all peripheral and most central depots. Peripheral lipoatrophy was more frequent in HIV-positive men than in controls (38.3% vs. 4.6%, P < 0.001), whereas central lipohypertrophy was less frequent (40.2% vs. 55.9%, P = 0.001). Among HIV-positive men, the presence of central lipohypertrophy was not positively associated with peripheral lipoatrophy (odds ratio = 0.71, CI: 0.47 to 1.06, P = 0.10). On MRI, HIV-positive men with clinical peripheral lipoatrophy had less subcutaneous adipose tissue (SAT) in peripheral and central sites and less visceral adipose tissue (VAT) than HIV-positive men without peripheral lipoatrophy. HIV-positive men both with and without lipoatrophy had less SAT than controls, with legs and lower trunk more affected than upper trunk. Use of the antiretroviral drugs stavudine or indinavir was associated with less leg SAT but did not appear to be associated with more VAT; nevirapine use was associated with less VAT.
Both peripheral and central subcutaneous lipoatrophy was found in HIV infection. Lipoatrophy in HIV-positive men is not associated with reciprocally increased VAT.
To investigate the psychosocial impact of lipodystrophy on the lifestyles of HIV positive patients on highly active antiretroviral therapy (HAART).
In-depth interviews were conducted with 14 HIV positive patients on HAART at an outpatient sexually transmitted infections (STI) and HIV clinic in central London. Qualitative data from interview transcripts were analysed using grounded theory to elicit key categories and subcategories.
Three main themes relating to lipodystrophy emerged: effect on the individual; impact on the social world of the individual; responses of the individual. Lipodystrophy had physical and psychological effects, ranging from bodily discomfort to low self esteem and depression. Owing to its physical manifestations it was viewed as a visible marker of HIV disease. At the level of social functioning, lipodystrophy led to problems with personal and family relationships, although having a partner was protective. Individuals reported narrowing their social world, in some cases to degrees of social isolation. Individual responses included changes in diet, increased exercise regimes, steroid use and plastic surgery (mainly collagen injections to the face). For those who had experienced serious illness related to HIV, there was a more sanguine acceptance of lipodystrophy as an unfortunate consequence of longevity and drug therapy
Health professionals need to address the psychosocial implications of lipodystrophy, including the ways in which it may affect different groups and their adherence to therapy. Formative evaluations are needed to assess the potential for targeted interventions.
Long-term antiretroviral therapy, while dramatically reducing HIV-related morbidity and mortality, is associated with metabolic and morphological changes. Peripheral fat loss, lipoatrophy, appears most associated with prolonged therapy with thymidine nucleoside analogues.
A randomized, open-label, comparative study of switching from a thymidine nucleoside analogue to either tenofovir disoproxil fumarate (DF) or abacavir in 105 individuals on successful antiretroviral therapy with clinically evident moderate to severe lipoatrophy.
Individuals were randomized to tenofovir DF (52) or abacavir (53). The switch was well tolerated and the majority of patients completed 48 weeks of study. One individual in the tenofovir DF group and three in the abacavir group discontinued due to drug-related adverse events. Both groups similarly maintained virological control. Limb fat mass increased similarly in both groups: mean increases by week 48 of 329 and 483 g in tenofovir DF and abacavir groups, respectively [mean 95% confidence interval for difference, -154.3 (range -492.8 to 184.3)]. This change from baseline was statistically significant in both groups (tenofovir DF, P = 0.01; abacavir, P = 0.0001). Mean total cholesterol, low density lipoprotein cholesterol and triglycerides improved modestly with switching to tenofovir DF but were unchanged with abacavir. The changes in these parameters were significantly greater in the tenofovir DF arm relative to abacavir.
Switching from a thymidine nucleoside analogue to either tenofovir DF or abacavir leads to significant improvement in limb fat mass over 48 weeks. Tenofovir DF may have modest advantages over abacavir for changes in lipids. Peripheral lipoatrophy, when clinically apparent, resolves slowly following treatment switching.
HIV-infected patients receiving antiretroviral therapy often develop changes in body fat distribution; the dominant change is reduction in sc adipose tissue (SAT). Because adipose tissue makes important hormones involved in whole-body energy metabolism, including leptin and adiponectin, we examined plasma concentrations and their relationship to regional adiposity measured by magnetic resonance imaging in 1143 HIV-infected persons (803 men and 340 women) and 286 controls (151 men and 135 women) in a cross-sectional analysis of the FRAM study.
Total and regional adiposity correlated positively with leptin levels in HIV-infected subjects and controls (P < 0.0001). In controls, total and regional adiposity correlated negatively with adiponectin. In HIV-infected subjects, adiponectin was not significantly correlated with total adiposity, but the normal negative correlation with visceral adipose tissue and upper trunk SAT was maintained. However, leg SAT was positively associated with adiponectin in HIV-infected subjects. Within the lower decile of leg SAT for controls, HIV-infected subjects had paradoxically lower adiponectin concentrations compared with controls (men: HIV 4.1 microg/ml vs. control 7.5 microg/ml, P = 0.009; women: HIV 7.8 microg/ml vs. control 11.6 microg/ml, P = 0.037). Even after controlling for leg SAT, exposure to stavudine was associated with lower adiponectin, predominantly in those with lipoatrophy.
The normal relationships between adiponectin levels and total and leg adiposity are lost in HIV-infected subjects, possibly due to changes in adipocyte function associated with HIV lipodystrophy, whereas the inverse association of adiponectin and visceral adipose tissue is maintained. In contrast, the relationship between adiposity and leptin levels appears similar to controls and unaffected by HIV lipodystrophy.
Impact of HIV infection and HAART on lipids in men
- S A Riddler
- E Smit
- S R Cole
- SA Riddler