HIV Lipodystrophy Research Articles

Soft tissue augmentation with PMMA-microspheres for the treatment of HIV-associated buttock lipodystrophy

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.

Immunohistochemical analysis of the expression of TNF-alpha, TGF-beta, and caspase-3 in subcutaneous tissue of patients with HIV Lipodystrophy Syndrome

IntroductionHIV Lipodystrophy Syndrome (HIVLS) is a multifactorial clinical expression that presents alterations in the metabolism and distribution pattern of body fat via immunological changes capable of disrupting homeostasis. This study aimed to analyze the degree of inflammatory, anti-inflammatory, and apoptosis activity in the subcutaneous tissue of patients, based on the expression of Tumor Necrosis Factor-α (TNF-α), Transforming Growth Factor-β (TGF-β), and caspase-3, respectively, and correlate them with clinical data and with each other. MethodsThis is a cross-analytical study. The biopsy of subcutaneous cellular tissue was performed on the right thigh of 19 patients with HIVLS who were attended to at a university hospital, and four people without HIV and lipodystrophy, for comparison. The type of lipodystrophy and the estimation of body fat were obtained during the consultation or obtained from medical charts. The cytokine expression was observed in the adipose tissue through the streptavidin-biotin peroxidase method, and analyzed by optical microscopy. ResultsDespite the mixed clinical form having been prevalent in both genders, men were more lipoatrophic and women were more lipohypertrophic. Men showed higher expression of TNF-α and caspase-3 than women. Patients with lipodystrophy had higher expression of TNF-α and caspase-3 and lower TGF-β, compared to the control group. The percentage of body fat was negatively correlated with the expression of TNF-α and caspase-3. Longer durations of infection and use of antiretroviral therapy (ARVT) were positively associated with the levels of TNF-α. The expression of caspase-3 and TGF-β was associated with higher levels of TNF-α. ConclusionRegardless of the clinical form, HIVLS is characterized by a chronic inflammatory process associated with the male gender, the percentage of body fat, and lipoatrophy manifestations. There is increased apoptotic activity in more inflamed tissues and there is correlation between TNF-α and TGF-β, which suggests a possible negative feedback mechanism between the inflammatory and anti-inflammatory activity.

RXRγ gene variants are associated with HIV lipodystrophy

HIV lipodystrophy (HIVLD), associated with combination antiretroviral therapy (cART), leads to metabolic and cardiovascular diseases. Nuclear receptors play a central role in lipid homoeostasis and drug disposition; their genetic variants may predispose an individual to the development of HIVLD. DNA samples obtained from cART-treated HIV-positive patients with (HIVLD+; 124) and without (HIVLD-; 56) HIVLD were genotyped for 77 single nucleotide polymorphisms in nine nuclear receptor genes. Statistical analysis was carried out using Haploview software and by logistic regression. Three single nucleotide polymorphisms in RXRγ (rs2134095, rs113471, rs2194899) and its haplotypes (HIVLD+, 54%; HIVLD-, 40.6%; P=0.02) showed significant association with HIVLD. Multivariate analysis identified time since diagnosis (P=0.001) and carriage of the RXRγ haplotype (P=0.02) to be independently associated with HIVLD. Genetic variation in RXRγ, a common binding partner of nuclear receptors that modulate lipid homoeostasis and drug disposition, may contribute to the development of HIVLD in cART-treated HIV patients. These results need replication in other cohorts.

In Vitro and In Vivo Effects of IGF-I on Adiposity in HIV-associated Metabolic Disease: A Pilot Study

We tested the effects of recombinant insulin-like growth factor-I (IGF-I) in an adipocyte model of HIV lipodystrophy and in an open label study on body composition and metabolism in patients with HIV lipodystrophy. The effects of IGF-I on ritonavir-induced adipocyte cell death were studied in vitro. We assessed lipid accumulation, IGF signaling, apoptosis, and gene expression. We conducted a 24-week open label trial of recombinant IGF-I in ten adults with HIV associated lipoatrophy. Laboratory assessments included glucose, insulin, lipids, and IGF-I. At weeks 0 and 24, body composition studies were performed including skinfold measurement, dual-energy x-ray absorptiometry, and computed tomography of the abdomen and thigh. In vitro, ritonavir increased delipidation and apoptosis of adipocytes, whereas co-treatment with IGF-I attenuated the effect. In the clinical study, subcutaneous adipose tissue did not increase in patients after treatment with IGF-I; however, there was a decrease in the proportion of abdominal fat (39.8 ± 7% vs. 34.6 ± 7%, p = 0.007). IGF-I levels increased with treatment (143 ± 28 μg/L at week 0 vs. 453 ± 212 μg/L at week 24, p = 0.002), whereas IGFBP-3 levels declined (3.554 ± 1.146 mg/L vs. 3.235 ± 1.151 mg/L, p = 0.02). Insulin at week 12 decreased significantly (90.1 ± 39.8 pmol/L vs. 33.2 ± 19.6 pmol/L, p = 0.002). There was a nonsignificant decrease in visceral adipose tissue (155.2 ± 68 cm² at week 0 vs. 140.6 ± 70 cm² at week 24, p = 0.08). Use of recombinant IGF-I may lower fasting insulin and abdominal fat in patients with lipoatrophy associated with HIV infection. Further evaluation of this agent for treatment of HIV-associated lipodystrophy may be warranted.

Rellenos de polialquilamida en lipodistrofia facial asociada al virus de la inmunodeficiencia humana: complicaciones oftalmológicas

Case reportA 54 year old male, who consulted for acute inflammatory palpebral edema. The patient has HIV infection (on antiretroviral treatment) and an associated facial lipodystrophy that was filled with polyalkylimide in both frontotemporal regions one year before. MRI revealed subcutaneous abscesses in the filled areas, which led to preseptal cellulitis. Complete remission was achieved with antibiotic therapy and monitoring. DiscussionPolyalkylimide is a hydrogel that is recently used as facial filler without FDA approval. Although it was believed to be safe and useful for treating HIV lipodystrophy, it is not exempt from adverse effects (infection, abscesses, granulomas) that can compromise the eye area.

Pathophysiology of GHRH-growth hormone-IGF1 axis in HIV/AIDS

Aberrations in GHRH-GH -IGF-I axis are common in the complex of HIV, HAART and AIDS. There are 2 distinct mechanisms at play in HIV and AIDS. One is primarly associated with development of lipodystrophy and results in complications such as chronic inflammation, insulin resistance, lipid and metabolic abnormalities. HIV lipodystrophy is found especially in those on highly active anti-retroviral therapy (HAART). The various processes involved in lipodystrophy result in the suppression of pituitary GH production. The mechanism of low GH levels relates to increased somatostatin tone, decreased Ghrelin, increased free fatty acids (FFA) and insulin resistance. On the other hand in AIDS wasting syndrome; elevated GH and low IGF-1 levels are seen suggesting GH resistance. The GHRH analog-Tesamorelin is the only treatment option, which is FDA approved for use in reduction of excess abdominal fat in patients with HIV-associated lipodystrophy. Although long-term clinical trials and experience is needed to further study the benefits and risks of Tesamorelin.

Increased Fdg Uptake in Association with Reduced Extremity Fat in HIV Patients

HIV lipodystrophy - characterized by peripheral lipoatrophy, with or without central fat accumulation - confers increased metabolic risk. However, the functional activity of HIV lipodystrophic tissue in relation to metabolic risk has yet to be fully explored in vivo through the use of non-invasive imaging techniques. This study assesses the relationship between FDG uptake in various fat depots and metabolic/immune parameters among subjects with HIV lipodystrophy. Lipodystrophic men on antiretroviral therapy underwent whole-body (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET)/computed tomography scans and detailed metabolic/immune phenotyping. FDG uptake in the subcutaneous adipose tissue (SAT) of the extremities (mean standardized uptake value [SUV] of the arm and leg SAT) was found to correlate with the degree of peripheral lipoatrophy (r=0.7; P=0.01). Extremity SAT FDG uptake was positively associated with homeostasis model assessment of insulin resistance (HOMA-IR; r=0.6; P=0.02) and fasting hyperinsulinaemia (r=0.7; P=0.01), while fat percentage of extremities was not. Furthermore, extremity SAT FDG uptake was significantly associated with CD4(+) T-cell count (r=0.6; P=0.05). In multivariate modelling for HOMA-IR, extremity SAT FDG uptake remained significant after controlling for body mass index and tumour necrosis factor-α (R(2) for model =0.71, P=0.02; SUV in the extremity SAT β-estimate 12.3, P=0.009). In HIV lipodystrophic patients, extremity SAT FDG uptake is increased in association with reduced extremity fat and may contribute to insulin resistance. Non-invasive assessments of in situ inflammation using FDG-PET may usefully complement histological and gene expression analyses of metabolic dysregulation in peripheral fat among HIV-positive patients.

A new scientific era in biomedicine – regenerative surgery based on lipotransplant. New therapeutic horizons for HIV-positive patients

Very often the psychological repercussions of lipodystrophy in HIV infected patients are important to a level that can reach reluctance to antiretroviral therapy or lead to depression and anxiety. In some patients' opinion, it is easier to live with HIV than with lipodystrophy. The facial appearance is perceived by the patient and the society as a stigma of this particular condition, with all negative consequences. We know that HIV-related lipodystrophy (first described in '97 and '98) is expressed by peripheral atrophy of the face, limbs and buttocks, simultaneous with central fat accumulation (visceral), as well as in the breasts, neck and dorsocervical area (the so-called “buffalo hump”). These features coexist with subcutaneous lipomas and metabolic disturbances such as insulin resistance, hypercholesterolemia and hypertriglyceridemia. Although the distribution of the adipose tissue is unbalanced (visceral increase and peripheral decrease) with overall fat loss, the mean body mass is preserved. The pathogenesis of HIV lipodystrophy remains unclear. Consistent studies (cohort and in vitro) of adipocytes, skeletal muscle and hepatocytes point toward a complex of factors involving antiretroviral theories, environmental and host-related aspects. The most effective treatment for facial lipodystrophy in HIV positive patients is still to be found; numerous treatment attempts have been made, based on changes in antiretroviral therapy, addition of other drugs (such as growth hormones, insulin, steroids), lipid-lowering drugs, diets or exercising, but these attempts have often proved disappointing. Even the nonresorbable or (slowly) resorbable fillers came with their high rate of complications. In this light, the newly born regenerative plastic surgery seems to be a very promising therapeutic solution. It is important to mention the brilliant scientific and practical contribution of pioneers in this field: S. Coleman, J.M. Serra-Renom, J. Fontdevila, M. Eisenmann-Klein, G. Rigotti, N. Pallua, P. Rubin, W. Futrell, R. Khouri, R. Mazzola, K. Yoshimura. Although facial fat grafting for HIV infected patients began in the late ’90s, the techniques (and instruments) have only recently become more refined, more precise, with a higher degree of predictability. And very importantly – there is more (although still not enough) science behind this approach, leading to a better understanding of the composition and behavior of the various cellular populations and other components generically called “adipose tissue”, which will soon probably be named “adipose organ”. The new researches and applications on adipose tissue revealed a whole fascinating universe of new therapies and scientific paths. “Adipocytes”, “preadipocytes”, “ADSC’s” (adipose-derived stromal cells), “niche”, scaffold, cell-cell interaction, blood circulating factors, paracrine factors, cell-matrix interaction, neurotransmitters, are key terms and, in the same time, key elements involved in regenerative surgery using fat transplant, leading to healing processes in facial HIV lipoatrophy. This novel type of closed surgery requires harvesting of the fat from the excessive deposits, which is then slowly centrifuged and transplanted with very fine instruments. The transplanted fat is stimulated with Fractional CO2 LASER (λ10600 nm) and with diode LASER (λ860 nm) as promising additional therapy due to LLLT (low level laser therapy). The LASER has at least two effects, acting to improve the quality of the skin (which is often very damaged) and optimize the take of the adipose graft. Due to the systemic effect of LLLT (and the derived photoproducts described by Mester and Oshiro), it is possible to record normalizations of remote tissue (cellular) disturbances. To improve skin condition and fat graft survival, one other additional simultaneous therapy can be performed – PRP (platelet-rich plasma), which contains growth factors. The science has still to deepen the good, often remarkable clinical results. The therapies based on self cellular regeneration with autologous products (adipose tissue transplant and stem cells, PRP) acting in synergy with light (LASER) energy and the science behind them, appear as an interesting, vast “station” for treating various conditions including HIV lipoatrophy, until the next scientific challenge, such as gene engineering therapy, becomes available.

Dual energy X-ray absorptimetry: Fundamentals, methodology, and clinical applications

Dual-energy X-ray absorptiometry (DXA; DEXA) is the technique of choice to diagnose osteoporosis and to monitor the response to treatment. It is also useful for measuring body composition. In recent years, new applications have been developed, including vertebral morphometry through the study of the lateral spine, prosthesis integration in orthopedics, and lipodystrophy in HIV+ patients, although its use in these cases is not well established. DXA densitometry is accurate and precise. It is essential to optimize each step of the diagnostic process, taking care to ensure the best acquisition, image analysis, and interpretation of the results. Thus, to obtain the greatest utility from DXA, radiologists need to know the technique, its indications, and its pitfalls. This article reviews the fundamentals, modalities, methods, and clinical applications of DXA.

Recovery From Lipodystrophy in HIV–infected Children After Substitution of Stavudine With Zidovudine in a Non-nucleoside Reverse Transcriptase Inhibitor–based Antiretroviral Therapy

Substitution of stavudine with zidovudine may lead to recovery from lipodystrophy (LD) in HIV-infected children. We prospectively followed HIV-infected children enrolled in an earlier LD study conducted between 2002 and 2004 at Chiang Mai University Hospital in northern Thailand. In 2006, stavudine was substituted with zidovudine. All children were evaluated by a clinical LD checklist modified from that of the European Pediatric LD study group together with waist/hip measurement at baseline and 24, 48, 72, and 96 weeks after substitution. The waist-to-hip ratios were converted to age- and sex-adjusted z scores based on normal ranges in healthy Thai children. Forty-five lipodystrophic children with 36 episodes of lipohypertrophy and 22 episodes of lipoatrophy were enrolled. By weeks 48 and 96 after substitution, 40% and 47% of lipohypertrophy resolved, whereas 59% and 73% of lipoatrophy resolved, respectively. The rate of resolution of lipoatrophy was higher than that of lipohypertrophy at 48 weeks after substitution and thereafter. Ninety-six weeks after changing to zidovudine therapy, 8 children still had LD (1 with both lipoatrophy and lipohypertrophy, 7 with lipohypertrophy). No clinically significant hematologic adverse event was observed. Substitution of stavudine with zidovudine resulted in decreased severity or resolution of LD among HIV-infected children and adolescents.

Absorciometría con rayos X de doble energía. Fundamentos, metodología y aplicaciones clínicas

Dual-energy X-ray absorptiometry (DXA; DEXA) is the technique of choice to diagnose osteoporosis and to monitor the response to treatment. It is also useful for measuring body composition. In recent years, new applications have been developed, including vertebral morphometry through the study of the lateral spine, prosthesis integration in orthopedics, and lipodystrophy in HIV+ patients, although its use in these cases is not well established. DXA densitometry is accurate and precise. It is essential to optimize each step of the diagnostic process, taking care to ensure the best acquisition, image analysis, and interpretation of the results. Thus, to obtain the greatest utility from DXA, radiologists need to know the technique, its indications, and its pitfalls. This article reviews the fundamentals, modalities, methods, and clinical applications of DXA.

Deiodinase 2 Expression Is Increased in Dorsocervical Fat of Patients with HIV-Associated Lipohypertrophy Syndrome

The pathogenesis and function of dorsocervical sc adipose tissue (DSAT) accumulation in HIV-infected patients is not known. Previous investigations using either UCP-1 expression or positron emission tomography have been inconclusive as to whether this depot represents brown adipose tissue (BAT). We investigated DSAT gene expression, including DIO2, a deiodinase that contributes to increased thermogenesis in brown fat, and simultaneously determined [¹⁸F]fluorodeoxyglucose ([¹⁸F]FDG) uptake in lipodystrophic HIV and healthy control subjects. Thirteen HIV-infected and three non-HIV-infected men were recruited. HIV-infected subjects had evidence of significant lipodystrophy, including fat atrophy of the face, arms, and legs, and/or fat accumulation of the neck and abdomen. Subjects were cooled, followed by [¹⁸F]FDG positron emission tomography/computed tomography, fat biopsy of DSAT, and measurement of resting energy expenditure (REE). HIV-infected subjects were characterized as lipohypertrophic and lipoatrophic and compared. Mean standardized uptake value of [¹⁸F]FDG and UCP-1 expression were not significantly different in DSAT among the groups. However, lipohypertrophic subjects demonstrated increased expression of DIO2 in DSAT compared with lipoatrophic subjects (P = 0.03). Among HIV-infected patients, DIO2 expression was strongly related to REE (r = 0.78, P = 0.002) and was a predictor of REE in multivariate modeling controlling for age, TSH, and lean body mass (r² = 0.79, P = 0.008). One control subject demonstrated typical BAT in the supraclavicular area. Adipose tissue accumulating in the dorsocervical area in HIV lipodystrophy does not appear to be classical BAT. However, DIO2 expression is increased in DSAT among patients with HIV lipodystrophy, particularly those with increased visceral adiposity, and is positively associated with energy expenditure.

Biochemical Manifestation of HIV Lipodystrophy Syndrome

Highly active anti-retroviral therapy (HAART), including protease inhibitors (PI) have led to dramatic improvements in the quality and quantity of life in patients with acquired immunodeficiency syndrome (AIDS). However, a significant number of AIDS patients on HAART develop characteristic changes in body fat redistribution referred to as lipodystrophy syndrome (LDS). Features of LDS include hypertrophy in the neck fat pad (buffalo hump), increased fat in the abdominal region (protease paunch), gynecomastia and loss of fat in the mid-face and extremities. The aim of this paper is to review the current knowledge regarding this syndrome. This article reviews the published investigations on biochemical manifestation of HIV lipodystrophy syndrome. It is estimated that approximately 64% of patients treated with PI will experience this syndrome. Biochemically, these patients have increased triglycerides (Trig), total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C) and extremely low high-density lipoprotein-cholesterol (HDL-C). It is hoped that awareness of this syndrome would aid in early diagnosis and better patient management, possibly leading to a lower incidence of cardiovascular complications among these patients.

HIV Lipodystrophy more Prevalent in Women than Men in Tamil Nadu, India

Background: As antiretroviral therapy (ART) becomes more available to the HIV infected population in rural areas in India, it is important to determine the prevalence of its long term complications. Therefore, it was proposed to find out the prevalence of lipodystrophy in patients receiving ART and compare the gender dif ferences. Material and methods: In this cross sectional study, consenting HIV-infected patients on ART visiting Namakkal District Head Quarters Hospital, Tamil Nadu, India, were recruited. They were on generic first-line fixed dose combinations of ART. Sociodemographics, anthropometric measurements, ART regimens and duration of treatment were recorded. Patients’ self-perception of lipodystrophy was obtained using standardized questionnaires and clinically confirmed by the physician. An overnight fasting blood was drawn to determine serum lipids levels. Statistical analysis included Chi-square test, student t-test and Mann Whitney U test. Results: There were 145 HIV-infected subjects (46.9% males, 53.1% females) receiving ART for a mean 29.4 months. Mean age of the males were 38.18 ± 8.85 and for the females, it was 33.34 ± 6.20. The mean body mass index (BMI) for the males was 21.95 ± 3.94 kg/m 2 while for the females it was 21.14 ± 3.54 kg/m 2 . The overall prevalence of lipodystrophy was 60.69%; 22.72% with lipohypertrophy, 51.14% with lipoatrophy, and 22.72% with mixed pattern. Women had a higher prevalence of lipodystrophy than men (p=0.004). Lipoatrophy was higher in females (p=0.015) and mixed pattern (p=0.015). There was a higher prevalence of facial atrophy, fat loss in arms, fat loss in legs and fat loss in buttocks among women compared to men. Women with lipodystrophy had higher BMI, CD4 counts, VLDL cholesterol and triglycerides. Conclusion: Women had significantly higher rates of generalized lipodystrophy and particularly lipoatrophy when compared with men taking first-line antiretroviral regimen. Compared with women without lipodystrophy, those with lipodystrophy had lipid abnormalities.

Antiretroviral drugs alter adipocyte metabolism: a possible role for polyunsaturated fatty acids in mitigating HIV lipodystrophy

Antiretroviral drugs alter adipocyte metabolism: a possible role for polyunsaturated fatty acids in mitigating HIV lipodystrophy

Psychological morbidity and facial volume in HIV lipodystrophy: Quantification of treatment outcome

HIV lipoatrophy is a stigmatizing condition associated with significant psychological morbidity. The aim of this study was to evaluate change in facial volume and psychological morbidity following treatment with autologous fat, Sculptra and Bio-alcamid. HIV LD patients were treated based on a clinical assessment in a prospective, observational study. 3-D images were obtained pre-operatively then at 2, 6 and 12 months post-operatively using the DI3D system. Volume changes were measured using DI3D software. The DAS-24 and HADS were used to assess psychological morbidity at similar time intervals. Forty-eight patients with HIV LD were treated: 16 patients had Bio-alcamid, 20 patients received Sculptra and 12 patients underwent fat transfer. The mean injected volume of Bio-alcamid was 25.5 cc which was comparable to the measured volume change at follow-up. The mean injected volume of fat was 20.1 cc, which did not differ from the measured volumes at 2 months. There was a mean reduction in measured volume change to11.2 cc at 6 months and 10 cc at 12 months. For Sculptra, the mean volume change compared to baseline was 8.7 cc at 2 months, increasing to 12.6 cc at 6 months and 12.3 cc at 12 months. ANOVA tests demonstrated no difference in psychological outcomes between groups. There was a significant improvement in DAS-24 scores compared to baseline for all 3 groups. No correlation between change in facial volume and psychological measures was demonstrated. Change in 3-D measured facial volume for all 3 groups was seen. Treatment was associated with improved body image perception.

Progressive right lower extremity enlargement

The patient and clinicians were concerned about the right lower extremity when in fact MRI showed the diseased extremity to be the left. The MR images (Figs. 1 and 2) show loss of subcutaneous fat throughout the left lower extremity with relative sparing of the muscle mass and medial thigh subcutaneous fat, accounting for the asymmetric size of the lower extremities and the misleading clinical appearance of an abnormally enlarged right lower extremity. The MRI distribution of subcutaneous fat loss of the left extremity was felt to be consistent with the diagnosis of lipodystrophy and in this patient attributed to adult onset dermatomyositis, which has been previously associated with lipodystrophy [1–3]. In addition, increased T2 signal on the STIR sequence within the subcutaneous tissues, particularly overlying the lateral left leg are indicative of active disease. Lipodystrophies are a group of disorders characterized by the loss of adipose tissue from various parts of the body, and have been categorized as being congenital or acquired and further subcategorized as generalized, partial, or localized [4]. The generalized varieties include congenital generalized lipodystrophy (Berardinelli–Seip syndrome) and acquired generalized lipodystrophy. Berardinelli–Seip syndrome is a rare autosomal recessive disorder in which there is a complete absence of adipose tissue at birth, while acquired generalized lipodystrophy manifests in late childhood and adolescence. Partial lipodystrophies include familial partial lipodystrophy (Dunnigan variety), which presents at onset of puberty, and acquired forms, which have been linked to HIV, drug use, and various autoimmune diseases. Localized forms of lipodystrophy are most often related to trauma, drug use, and autoimmune causes [4]. Patients affected by lipodystrophy are predisposed to insulin resistance. The central cause of morbidity and mortality in patients with lipodystrophy are diabetes mellitus and its long-term complications, including recurrent pancreatitis related to hypertriglyceridemia, chronic liver disease related to hepatic steatosis, and atherosclerotic disease [5]. Acquired lipodystrophies are the most common subtype, with HIV lipodystrophy accounting for over 100,000 cases of lipodystrophy in the United States alone [5]. The typical pattern of HIV lipodystrophy is loss of subcutaneous fat in the face and extremities, with compensatory circumferential adipose deposition in the submental (double chin), dorsocervical spine (buffalo hump), chest, and intra-abdominal regions [6]. This is in contradistinction to acquired partial lipodystrophy (Barraquer–Simons syndrome) and acquired generalized partial lipodystrophy. Acquired partial lipodystrophy is very rare (250 cases in the English literature), and characterized by subcutaneous adipose loss involving the face, neck, arms, chest, and abdomen, with compensatory circumferential adipose deposition in the thighs and lower legs [5]. Acquired generalized lipodystrophy (80 reported cases in the English literature) is characterized by circumThe case question and presentation can be found at doi:10.1007/ s00256-011-1271-7.

Brown Fat Activity Is not Apparent in Subjects With HIV Lipodystrophy and Increased Resting Energy Expenditure

The HIV lipodystrophy (LD) syndrome is associated with increased resting energy expenditure (REE), but the basis of this hypermetabolism has not been determined. The objective of this pilot study was to determine if brown fat is activated in subjects with HIV LD and increased REE. In this descriptive study of four subjects with HIV LD and marked hypermetabolism, REE was measured by indirect calorimetry and brown fat activity was determined by (18)F-fluorodeoxyglucose (FDG) positron-emission tomography (PET) combined with anatomic computed tomography (CT). Brown fat activity was not apparent in any subject with HIV LD and resting hypermetabolism. Therefore, brown fat activation is unlikely to be the principal cause of the increased REE associated with the HIV LD syndrome. Evidence of adaptive thermogenesis has been demonstrated in this syndrome, but this study suggests that tissues other than brown adipose tissue (BAT) are responsible. Further understanding of the chronic hypermetabolism associated with HIV LD could provide new insights into the regulation of energy balance.

Therapy for HIV

Initial therapies for HIV infection comprised nucleoside analogues, but as single or dual agents, they failed to prevent disease progression. When a new class of drug was introduced, the protease inhibitors, an effective triple therapy became possible-namely, highly active antiretroviral therapy, or HAART. HAART reduced viral replication almost completely and enabled immune system recovery. The probability of classical infections and tumors attributed to HIV were dramatically reduced, and life expectancy correspondingly increased. The initial disadvantages of HAART included the need for strict adherence to prevent drug resistance, the cost that initially precluded their widespread use in the developing world, and the short- and long-term side effects. One of the most disabling long-term complications was HIV lipodystrophy, which in extreme cases lead to severe peripheral fat wasting and central fat gain. In recent years, many of these disadvantages have been addressed: Once-daily drug combinations improve adherence; global access to HAART has been markedly improved; and new drugs enable patients to avoid many of the initial side effects. Future research will determine at what CD4 count HAART should be initiated, and new approaches such as immunotherapeutic HIV vaccines are being tested with the aim to delay or obviate the need for antiretroviral drugs.

Adipogenic gene variants in patients with HIV-associated lipodystrophy

Although highly active antiretroviral therapy (HAART) has been hugely beneficial in the treatment of HIV, HIV lipodystrophy (HIVLD) associated with HAART is a serious adverse effect, with long-term consequences including metabolic disturbances and an increased risk of atherosclerotic disease. Although HIVLD is clearly related to the drug regimen, individual susceptibility also plays a role. We hypothesized that variation in genes regulating adipogenesis, and in those implicated in inherited forms of lipodystrophy, may predispose to the development of HIVLD. DNA samples were obtained from 180 HAART-treatedHIV+ patients: 124 with HIVLD (HIVLD+) and 56 without HIVLD (HIVLD-). Diagnosis of HIVLD was carried out by clinician's confirmation of patient self-report. High-throughput genotyping using Sequenom was used to screen 62 single nucleotide polymorphisms (SNPs) in eight genes involved in adipogenesis and inherited forms of lipodystrophy. Statistical analysis was performed using Haploview. Multivariate analysis (logistic regression) was used to identify independent predictors of HIVLD development in HAART-treated patients. SNPs in two adipogenesis regulators, LPIN1 and CEBPα, showed a significant association with HIVLD whereas a SNP in ZMPSTE24, a zinc metalloproteinase involved in prelamin A processing, showed a trend toward significance. Multivariate analysis identified time since HIV diagnosis (P=0.001) and carriage of more than one associated allele (P=0.008) to be the most significant independent predictors for the development of HIVLD. Genetic variation in key regulators of adipogenesis could interfere with fat storage and metabolism contributing to the development of HIVLD in HAART-treated HIV patients. These results need replication in other cohorts.