Central Lipohypertrophy Research Articles

Lipohypertrophy and metabolic disorders in HIV patients on antiretroviral therapy: a systematic multidisciplinary clinical approach.

IntroductionMorphological and metabolic complications in HIV patients on antiretroviral therapy remain a challenge. While new cases of lipoatrophy (LA) disappear, irreducible central lipohypertrophy (LH) and metabolic complications require highly specialized management. We described a day hospital dedicated to lipodystrophy (LD) and metabolic disorders in HIV patients on treatment in Geneva, Switzerland, with a focus on LH.Materials and MethodsThe “Groupe Lipo & Metabolism” is a multidisciplinary consultation where patients undergo a standard evaluation including questionnaire, physical examination, dual-energy x-ray absorptiometry (DEXA) and L5-level CT scans, blood tests and consultations with various specialists. Based on prospectively maintained data, we describe clinical, biological and radiological characteristics of patients ≥18 years who attended the consultation between 2008 and 2013. We defined LH by CT scan, the gold standard method, as abdominal visceral adipose tissue (VAT) ≥130 cm2, value associated with increased risk of cardiovascular event.ResultsA total of 195 patients attended the consultation during study period. Reasons for referral included LH in 28.3%, LA in 25% and mixed syndrome in 15.5% of cases. Metabolic disorders accounted for 19% of referrals with or without LD features. Among patients with a CT scan performed (n=183), 46 (25%) had LH with a VAT ≥130 cm2. In this population, mean age was 49.1 years and 53.6% were male. HIV viral load was <50 cp/ml in 87% of patients. Mean body mass index was 24.6 kg/m2. Mean waist to hip ratio (WHR) was 0.98 for males and 0.89 for females. A total of 9.8%, 29.5% and 35% of patients had abnormal levels of total cholesterol (≥6.5 mmol/L), triglycerides (≥2.0 mmol/L) and HDL cholesterol (≤1.0 mmol/L), respectively. Mean fasting glycaemia was 5.7 mmol/L and HbA1c was >6% in 10.5% of patients. Vitamin-D level was <75 nmol/L in 70.7% of patients. Respectively 31.2% and 12.1% of patients had osteopenia and osteoporosis on the spine and 44.8% and 6.6% on the hip neck. Factors associated with a VAT≥130 cm2 included male gender (OR 3.7 [95% CI 1.7–8.2] p<0.001), triglycerides ≥2 mmol/L (OR 2.6 [95% CI 1.3–5.4] P<0.01) and increase in BMI category (OR 1.8 [95% CI 1.2–2.8] p<0.01).ConclusionsLipohypertrophy is a prevalent feature of fat redistribution among HIV patients on treatment. Risk factors for LH include male gender, dyslipidemia and overweight. Glucose impairment and bone disorders are also common. A multidisciplinary approach is important to identify and promptly address these disorders.AcknowledgmentsThe “Groupe Lipo & Metabolism” team.

The natural history of HIV-associated lipodystrophy in the changing scenario of HIV infection.

In long-term HIV-infected patients, peripheral lipoatrophy (LA) and central lipohypertrophy (LH) appear to be related to the same insults (virus and antiretroviral drugs), but are likely to be associated with different fat depot physiologies. The objective of this study was to describe the natural history of lipodystrophy assessed using dual energy X-ray absorptiometry (DEXA) and computed tomography (CT) in a large HIV out-patients metabolic clinic. An observational retrospective study was carried out including HIV-infected patients recruited at the Metabolic Clinic of Modena, Modena, Italy, who were assessed for lipodystrophy and had at least two anthropometric evaluations using DEXA for leg fat per cent mass and abdominal CT for visceral adipose tissue (VAT). Factors associated with leg fat per cent and VAT changes were analysed using multivariable generalized estimating equation (GEE) regression models. A total of 6789 DEXAs and 7566 CT scans were evaluated in the observation period. A total of 1840 patients were included; the mean age was 45.2 ± 7.2 (standard deviation) years, 621 (34%) were women, and the median HIV infection duration was 176 (interquartile range 121-232) years. According to the GEE multivariable regression analysis, leg fat per cent evaluated with DEXA appeared to increase over calendar years (ß = 0.92; P < 0.001); moreover, a progressive increase in VAT was observed in the cohort (ß = 5.69; P < 0.001). No association with antiretroviral drugs was found. In our study, neither LA nor LH appeared to be associated with antiretroviral drug exposure. We observed a progressive increase in LH in HIV-infected patients over calendar years. This anthropometric change, together with loss of appendicular lean mass, could describe a physiological aging process in HIV-infected patients.

Investigating the effects of metabolic dysregulation on hair follicles: a comparison of HIV-infected women with and without central lipohypertrophy

Normal lipid metabolism and functioning of the peroxisome proliferator-activated receptor gamma (PPAR-gamma) in the sebaceous gland is critical to maintaining a normal hair follicle. Human immunodeficiency virus (HIV) infection affects lipid metabolism; some have hypothesized a link between PPAR-gamma function and lipodystrophy in HIV infection. Our objective was to determine whether lipodystrophy is associated with altered hair characteristics in HIV-infected women from the Women's Interagency HIV Study. Hair characteristics and scalp inflammation were assessed by an interviewer-administered questionnaire. Central lipohypertrophy and peripheral lipoatrophy were defined by self-report of moderate to severe fat gain in central body sites and fat loss in peripheral body sites, respectively confirmed by clinical examination. Additional covariates considered in the analyses included demographics, behavioral characteristics, medical history, and HIV-related factors. There were 1037 women with data on all study variables; 76 women reported central lipohypertrophy, while only four women reported lipoatrophy. Women with central lipohypertrophy were more likely to be older, had a self-reported history of injection drug use, statin medication use, diabetes, elevated cholesterol, and have self-reported less hair and shorter eyelashes. After adjustment for age, central lipohypertrophy was associated with shorter eyelashes (OR 2.3; 95% CI 1.4-3.8). Central lipohypertrophy was not associated with change in scalp hair texture or scalp inflammation in this cohort. Rather, we found an association between central lipohypertrophy and shorter eyelash length. This finding may be explained by an influence of prostaglandin E2 mediators on eyelash follicles.

Lipodystrophy and reversal of facial lipoatrophy in perinatally HIV-infected children and adolescents after discontinuation of stavudine

Lipodystrophy (LD) was evaluated in 205 children receiving antiretroviral therapy by a single investigator: 51 (24.9%) had LD; 46 peripheral lipoatrophy, three central lipohypertrophy and two combined type. All cases of peripheral and combined LD also had facial lipoatrophy. Serial photographs were provided by the families to confirm the severity of facial lipoatrophy. Forty-six (95.8%) children with peripheral or combined LD, and 75 (48.7%) without LD were exposed to stavudine (d4T) for a median duration of 45.9 versus 26.4 months (P = 0.005). In multivariate analysis, exposure to d4T for more than three months was the only factor associated with peripheral or combined LD (P < 0.001). Noticeable improvement of facial lipoatrophy was found in 11/48 (22.9%) children after a mean duration of 45.6 months following d4T discontinuation, mostly occurring during early adolescence.

Lipodystrophy, Insulin Resistance, and Adiponectin Concentration in HIV-Infected Children and Adolescents

Alterations of fat distribution and insulin resistance are associated with increased risk of metabolic derangements and cardiovascular disease. HIV-infected adult patients on antiretroviral treatment often show lipodystrophy, insulin resistance and hypoadiponectinemia, but data in children are controversial. We investigated serum adiponectin concentration in a cohort of HIV-infected youths, and we assessed the relationships with lipodystrophy and insulin resistance. We studied 36 HIV-infected patients (aged 5.0 - 19.4 years), and 171 healthy subjects (aged 4.9 - 17.9 years) for adiponectin measurements. All patients underwent body composition assessment by dual-energy x-ray absorptiometry, and an oral glucose tolerance test to determine the fasting insulin concentration, the insulin area under the curve (AUC), and the HOMA index. Adiponectin serum concentration was measured by an immunoenzymatic assay. Sixteen patients had central fat accumulation, 6 had peripheral lipoatrophy, 5 had a mixed phenotype, and the remaining 9 were non-lipodystrophic. Fasting insulin, insulin AUC, and HOMA index were significantly higher in patients with central fat adiposity and mixed phenotype than in the other two groups. The patients of the former two groups had adiponectin concentration much lower than healthy controls, and patients with peripheral lipoatrophy or normal phenotype had normal concentration. Low adiponectin concentration is associated to central fat and mixed lipohypertrophy, and to signs of insulin resistance in HIV-infected youths. Strict monitoring of metabolic and cardiovascular evolution should be performed in these patients.

Ethnicity and Gender Differences in Lipodystrophy of HIV-Positive Individuals Taking Antiretroviral Therapy in Ontario, Canada

Purpose: This study assessed ethnicity and gender differences in prevalence, type, and severity of antiretroviral-associated lipodystrophy in HIV-positive individuals in Ontario. Methods: This was a cross-sectional analysis of the Ontario Cohort Study (OCS), a prospective study of HIV-positive patients in Ontario. Lipodystrophy was defined as at least 1 major or 2 minor self-reported changes of peripheral lipoatrophy and/or central lipohypertrophy. Prevalence, type, and severity were compared by ethnicity (Black, White, or Other) and gender. Univariate and multivariate logistic regression analyses identified predictors of lipodystrophy. Results: Data were available for 778 participants (659 men, 119 women). There were 517 Whites, 121 Blacks, and 140 patients of Other ethnicities. In univariate analyses, Whites reported more peripheral lipoatrophy (P = .004) and abdominal lipohypertrophy (P = .04); these ethnic differences were observed in males (P = .05 and P = .03, respectively) but not females. Males reported more peripheral lipoatrophy (P = .01), whereas females had more central lipohypertrophy (P < .0001) and mixed fat redistribution (P < .0001). Multivariable regression analyses revealed Black women to be most vulnerable to lipodystrophy (P = .02), particularly lipohypertrophy (P < .0001). Conclusions: Ethnicity and gender are important factors influencing lipodystrophy. Combining lipoatrophy and lipohypertrophy into a single entity is not appropriate. Black women were most vulnerable to lipohypertrophy, which has important implications for antiretroviral therapy roll-out in Africa.

Lipodystrophy and metabolic complications of highly active antiretroviral therapy

To assess the metabolic drug toxicities of first-line, World Health Organization (WHO)-recommended generic highly active antiretroviral therapy (HAART) regimens, to estimate the prevalence of body fat redistribution and to identify associated risk factors. Cross-sectional observational study. During 3 month period, 52 HIV infected children (25 on HAART; 27 not on HAART) were assessed. Their sociodemographic, clinical, and immunological data was recorded. Children were examined or the signs of fat redistribution (peripheral lipoatrophy and central lipohypertrophy). Liver function tests, fasting blood sugar, lipid profile, serum amylase, serum lactate, blood pH and bicarbonate levels were done in all patients. Twenty-two patients were on stavudine and three on zidovudine based HAART. None of the patients ever received any protease inhibitor. There were no cases of clinical or immunological failure. Children on HAART had significantly lower weight for age and body mass index but the mean height for age was similar between study groups. Only two cases of peripheral lipoatrophy were observed. Hypercholesterolemia was observed in four children on HAART but none without therapy. Hypertriglyceridemia was observed in three children on HAART and seven without therapy. Four cases of asymptomatic mild hyperlactatemia were observed. No case of any hyperglycemia or liver impairment was observed. Metabolic abnormalities and lipodystrophy are emerging complications of HAART in Indian children and needs very close follow up. Future studies with larger sample size and longitudinal model are recommended.

Lipodystrophy and metabolic changes in HIV-infected children on non-nucleoside reverse transcriptase inhibitor-based antiretroviral therapy

Highly active antiretroviral therapy (HAART) has recently been implemented in Thailand. Its long-term effects have not been clearly evaluated. The objective of this study was to estimate the prevalence of lipodystrophy (LD) and other metabolic changes in HIV-infected children receiving HAART. Ninety children who began HAART (either nevirapine or efavirenz, together with lamivudine and stavudine) were prospectively followed. LD was assessed by waist-to-hip ratio and LD checklist. Hypercholesterolaemia was defined as total cholesterol > 200 mg/dl and low-density lipoprotein cholesterol > 130 mg/dl. Low levels of high-density lipoprotein cholesterol (HDL-c), hypertriglyceridaemia and hyperglycaemia were defined as HDL-c < 40 mg/dl, triglyceride > 200 mg/dl and plasma glucose > 110 mg/dl, respectively. The mean age at entry was 7.6 (SD 2.9) years. Fifty-three children received nevirapine- and 37 received efavirenz-based HAART. The prevalence of LD was 9%, 47% and 65% at 48, 96 and 144 weeks after HAART initiation, respectively. Patterns of LD at week 144 were central lipohypertrophy (46%), peripheral lipoatrophy (20%), and combined type (34%). A higher prevalence of LD was found among females (61% versus 39%; P = 0.04) and those with more advanced disease (CDC category B or C) at baseline (73% versus 51%; P = 0.04). There was no difference in prevalence of LD between the two regimens. At 144 weeks, fasting hypertriglyceridaemia was detected in 12%, hypercholesterolaemia in 11%, and increased plasma glucose in 4% of children. Low HDL-cholesterolaemia decreased from 94% at baseline to 12% at week 144 (P < 0.01). More than half of the children developed LD at 144 weeks after HAART. Dyslipidaemia occurred in 11-12% of children.

Therapy Insight: body-shape changes and metabolic complications associated with HIV and highly active antiretroviral therapy

Increasingly effective therapies for HIV infection are now available. These treatments, referred to collectively as highly active antiretroviral therapy, comprise various combinations of anti-HIV drugs from different drug classes. Recently, a range of metabolic complications have emerged as important toxicities in treated patients. Complications present as abnormalities of body-fat mass distribution in association with an often significant dyslipidemia and glucose homeostasis dysregulation. The body-shape changes, manifesting as peripheral lipoatrophy or central lipohypertrophy, can have a negative impact on quality of life and consequently on adherence to treatment. The combination of central lipohypertrophy, dyslipidemia and insulin resistance is associated with accelerated rates of atherosclerosis and other potentially significant long-term effects. The pathogenesis of these effects is complex and is still being actively investigated. Possible contributing factors relate to host characteristics, HIV viral parameters and specific effects of anti-HIV drugs on adipose-tissue biology and on intermediary metabolism. Management of these complications involves manipulation of the anti-HIV drugs using an understanding of their particular effects on lipid and glucose metabolism, in association with standard therapeutic interventions. Individualized approaches, taking into consideration quality-of-life issues, and assessment of potential cardiovascular risks, are now an important component of effective care of HIV-infected patients.

Body Fat Changes and Lipodystrophy in HIV-infected Children

Body Fat Changes and Lipodystrophy in HIV-infected Children

Fat Distribution in Women With HIV Infection

Both peripheral fat loss and central fat gain have been reported in women with HIV infection. We determined the fat changes that are specific to HIV infection in women. HIV-infected and control women from the study of Fat Redistribution and Metabolic Change in HIV Infection (FRAM) were compared. Lipoatrophy or lipohypertrophy was defined as concordance between participant report of fat change and clinical examination. Whole-body magnetic resonance imaging measured regional adipose tissue volumes. The relationship among different adipose tissue depots was assessed. Factors associated with individual depots were analyzed using multivariate linear regression. HIV-infected women reported more fat loss than controls in all peripheral and most central depots. Peripheral lipoatrophy was more frequent in HIV-infected women than controls (28% vs. 4%, P < 0.001), whereas central lipohypertrophy was similar (62% vs. 63%). Among HIV-infected women, those with central lipohypertrophy were less likely to have peripheral lipoatrophy (odds ratio, 0.39; 95% confidence interval, 0.20 to 0.75, P = 0.006) than those without central lipohypertrophy. On magnetic resonance imaging, HIV-infected women with clinical peripheral lipoatrophy had less subcutaneous adipose tissue (SAT) in peripheral and central sites and less visceral adipose tissue (VAT) than HIV-infected women without peripheral lipoatrophy. Compared with controls, HIV-infected women had less SAT in the legs, regardless of the presence or absence of lipoatrophy. However, those without lipoatrophy had more VAT and upper trunk SAT than controls. Use of the antiretroviral drug stavudine was associated with less leg SAT but was not associated with VAT. The use of highly active antiretroviral therapy, however, was associated with more VAT. Peripheral lipoatrophy occurs commonly in HIV-infected women but is not associated with reciprocally increased VAT or trunk fat.

Obstacles to Needle Exchange Participation in Rhode Island

Objective: Both peripheral fat loss and central fat gain have been reported in women with HIV infection. We determined the fat changes that are specific to HIV infection in women. Methods: HIV-infected and control women from the study of Fat Redistribution and Metabolic Change in HIV Infection (FRAM) were compared. Lipoatrophy or lipohypertrophy was defined as concordance between participant report of fat change and clinical examination. Whole-body magnetic resonance imaging measured regional adipose tissue volumes. The relationship among different adipose tissue depots was assessed. Factors associated with individual depots were analyzed using multivariate linear regression. Results: HIV-infected women reported more fat loss than controls in all peripheral and most central depots. Peripheral lipoatrophy was more frequent in HIV-infected women than controls (28% vs. 4%, P < 0.001), whereas central lipohypertrophy was similar (62% vs. 63%). Among HIV-infected women, those with central lipohypertrophy were less likely to have peripheral lipoatrophy (odds ratio, 0.39; 95% confidence interval, 0.20 to 0.75, P = 0.006) than those without central lipohypertrophy. On magnetic resonance imaging, HIV-infected women with clinical peripheral lipoatrophy had less subcutaneous adipose tissue (SAT) in peripheral and central sites and less visceral adipose tissue (VAT) than HIV-infected women without peripheral lipoatrophy. Compared with controls, HIV-infected women had less SAT in the legs, regardless of the presence or absence of lipoatrophy. However, those without lipoatrophy had more VAT and upper trunk SAT than controls. Use of the antiretroviral drug stavudine was associated with less leg SAT but was not associated with VAT. The use of highly active antiretroviral therapy, however, was associated with more VAT. Conclusions: Peripheral lipoatrophy occurs commonly in HIV-infected women but is not associated with reciprocally increased VAT or trunk fat.

Fat Distribution in Men With HIV Infection

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.

Cardiovascular disease in HIV-positive patients

Cardiovascular disease in HIV-positive patients

Antiretroviral therapy, fat redistribution and hyperlipidaemia in HIV-infected children in Europe.

To estimate prevalence of body fat redistribution and dyslipidaemia in HIV-infected children and to assess associated risk factors, ultimately to inform the definition of lipodystrophy in children. Cross-sectional observational study. During a 2-3 month period, 477 HIV-infected children aged >or= 3 years (median 9.78; range, 3-18) in 30 paediatric HIV clinics were assessed at their first visit. Sociodemographic, clinical and immunological data were recorded and the presence or absence of clinical signs of fat redistribution (peripheral lipoatrophy and central lipohypertrophy) determined according to an agreed protocol. Laboratory indicators of lipid/glucose metabolism were recorded for all children in 18 centres. Prevalence was 26.0% [95% confidence interval (CI), 22.1-30.2] for any fat redistribution, 8.81% (95% CI, 6.42-11.7) for central lipohypertrophy, 7.55% (95% CI, 5.34-10.3) for peripheral lipoatrophy and 9.64% (95% CI, 7.15-12.7) for the combined subtype (more than one sign of each). Independent predictors of fat redistribution included Centers for Disease Control and Prevention class C disease, female gender, ever used versus never use of protease inhibitors and of stavudine. Increasing time since initiation of antiretroviral therapy was associated with increased severity of fat redistribution. In the metabolic assessment subgroup, 27% (95% CI, 21.6-32.7) of children had hypercholesterolaemia and 21% (95% CI, 16.4-26.6) hypertriglyceridaemia; however, significantly more children had fat redistribution in this subgroup than overall (31%). Approximately a quarter of children and adolescents could be taken to have signs of lipodystrophy, with clinical presentation and risk factors similar to those described in adults.

What is HIV-associated lipodystrophy? Defining fat distribution changes in HIV infection.

The prevalence of lipodystrophy in HIV infection reported in the early literature has varied widely due in part to the different methods used in assessing and defining lipodystrophy in studies. There remains a lack of clarity regarding whether the peripheral lipoatrophy and central lipohypertrophy initially described in HIV infection are a result of separate mechanisms or a single mechanism. We review the current methods used to assess and define lipodystrophy in HIV infection; the prevalence and incidence of lipodystrophy reported in the recent HIV literature; and future directions in elucidating the morphologic changes associated with HIV infection. Different methods of assessing and defining lipodystrophy continue to lead to varying prevalence and incidence rates in recent large cross-sectional and prospective studies. Recent studies that include a predominantly HIV-uninfected comparison group and utilize bi-directional surveys to describe fat loss and fat gain in both peripheral and central body sites suggest that there is an HIV-associated lipoatrophy that affects both peripheral and central sites. In one study that used objective measures to quantify fat such as magnetic resonance imaging, HIV-associated subcutaneous lipoatrophy appeared to predominate when compared with a healthy control group. Peripheral and central lipoatrophy affecting subcutaneous fat is emerging as the dominant morphologic change associated with HIV infection when compared with those without known HIV infection. Studies of lipodystrophy in HIV infection should focus on lipoatrophy using direct measures of fat when possible.

Incidence of lipoatrophy and lipohypertrophy in the women's interagency HIV study.

To estimate the incidence of lipoatrophy and lipohypertrophy among HIV-infected and HIV-uninfected women from the Women's Interagency HIV Study. Eight hundred fifteen women with semiannual data on self-report of bidirectional change in body fat, anthropometric measurements, weight, and bioelectric impedance analysis were included in a 30-month incidence analysis. Lipoatrophy and lipohypertrophy in both peripheral (arms, legs, and buttocks) and central (waist, chest, and upper back) sites were defined by self-report of either a decrease or an increase in a body fat region over the previous 6 months that was confirmed by a corresponding change in anthropometric measurement. Weight and total body fat increased in HIV-uninfected women but remained stable in HIV-infected women over 30 months. Among HIV-infected women, the incidence of peripheral (relative hazard, 2.1; 95% confidence interval [CI], 1.4-3.3) and central (relative hazard, 1.9; 95% CI, 1.2-2.8) lipoatrophy was about double that among HIV-uninfected women, after adjustment for age and race. The incidence of peripheral lipohypertrophy appeared lower among HIV-infected women than among HIV-uninfected women (relative hazard, 0.8; 95% CI, 0.6-1.1), while the incidence of central lipohypertrophy did not differ by HIV status. Of HIV-infected women with 2 of 4 lipodystrophy outcomes, most (81%) had combined peripheral and central lipoatrophy or combined peripheral and central lipohypertrophy. Only 14% of these women had both peripheral lipoatrophy and central lipohypertrophy. These prospective data suggest that lipoatrophy, affecting both peripheral and central sites, predominates in HIV-infected women. The simultaneous occurrence of peripheral lipoatrophy and central lipohypertrophy was uncommon.

HIV lipodystrophy: prevalence, severity and correlates of risk in Australia.

To establish the prevalence, severity and factors associated with the HIV lipodystrophy syndrome. Cross-sectional study of lipodystrophy conducted in high HIV caseload primary care sites and HIV outpatient clinics. A subset of patients was examined using dual energy X-ray absorptiometry (DEXA) and single cut abdominal computerized tomography (CT) at the L4 vertebral level to quantify regional and total body fat. Factors associated with lipodystrophy, lipoatrophy and lipohypertrophy were assessed using multiple logistic regression based on assignment of cases and non-cases. One thousand, three hundred and forty-eight patients (95% male) were surveyed, 20% had AIDS, the mean CD4 lymphocyte count was 486 cells/microL, and 55% had <500 HIV-1 RNA copies/mL. Most participants (87%) had previously received or were currently receiving combination antiretroviral therapy, 73% with at least one protease inhibitor (PI) and 14% a non-PI-containing regimen. Lipodystrophy prevalence was 53% and of these, 55% reported both peripheral lipoatrophy and central lipohypertrophy, 31% experienced peripheral lipoatrophy only and 14% had central lipohypertrophy only. The prevalence of any body habitus change was 62% in PI-experienced patients, 33% in PI-naive patients and 21% in antiretroviral-naive patients. Lipodystrophy severity was less in antiretroviral-naive patients and most severe in PI-experienced patients. Increasing severity of lipodystrophy was both positively and significantly correlated with elevated liver enzymes, decreased testosterone levels, decreased skin-fold thickness, lower levels of total and peripheral fat (DEXA) and higher levels of visceral fat (CT). Lipodystrophy was also significantly associated with increasing age, symptomatic HIV disease, effective viral suppression, and increasing duration of therapy with both nucleoside reverse transcriptase inhibitors and PIs. The prevalence and severity of lipodystrophy reflects both length and type of treatment with antiretroviral therapy and is associated with decreased testosterone, increases in liver enzymes and greater suppression of HIV RNA. The reports of lipodystrophy in a small percentage of antiretroviral-naive patients suggests that factors other than antiretroviral therapy may be involved in the aetiology of this syndrome or that some conditions, such as wasting or age-associated obesity, may mimic lipoatrophy and lipohypertrophy, respectively.