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PubMed2002

Risk factors for the HIV-associated lipodystrophy syndrome in a closed cohort of patients after 3 years of antiretroviral treatment.

OBJECTIVE: To identify prevalence and risk factors associated with the HIV-associated lipodystrophy syndrome (HIVLD) after 3 years of antiretroviral therapy, to investigate the diagnostic value of anthropometric measures and to assess the impact of HIVLD on quality of life. DESIGN AND METHODS: A prospective, cross-sectional, multicentre, observational, cohort study was performed in 27 German teaching hospitals, nonacademic hospitals and private practices. A total of 221 HIV-positive patients commencing antiretroviral therapy between July and September 1996 were studied. The main outcome measure was lipodystrophy, defined as otherwise unexplained truncal fat accumulation and/or fat loss in face or extremities. The analysis consisted of multiple logistic regression models, receiver operating characteristics (ROC) curves for anthropometric measures and visual analogue scales for quality of life. RESULTS: The prevalence of HIVLD after 3 years was 34%. The following variables were independently associated with HIV-LS: stavudine use > 12 months [odds ratio (OR) 2.1, 95% confidence interval (CI) 1.1-3.9], CD4 count nadir < 200 cells/microL (OR 2.2, CI 1.1-4.6), hypertriglyceridaemia (OR 2.3, CI 1.3-4.2) and nonnucleoside reverse transcriptase inhibitor (NNRTI) intake > 12 months (OR 0.2, CI 0.04-0.87). No cut-off point was found for anthropometric indices with a sensitivity and specificity of > or = 0.8. The mean visual analogue ratings for impaired quality of life, on a scale of 0-10, were: 5.2 (self-esteem), 2.9 (social contacts), 4.2 (sexuality) and 3.5 (daily activities). CONCLUSIONS: These findings suggest a multifactorial aetiology for HIVLD. Stavudine use and a CD4 count below 200 cells/microL may be associated with an increased risk for the development of HIVLD. In contrast, NNRTI treatment may be associated with a reduced risk. Anthropometric indices were found to be insufficient as a diagnostic tool. Quality of life was severely affected by HIVLD.

Adult↗
PubMed2001

L-Carnitine in the treatment of HIV-associated lipodystrophy syndrome.

The objective of this pilot study was to assess the effect of L-carnitine on the course of the HIV-associated lipodystrophy syndrome. Twelve patients presenting with combined atrophic and hypertrophic changes of body fat were treated with L-carnitine 1000 mg bid for 3 months. No marked improvement of the body changes was observed. However a reduction in serum cholesterol levels, but not triglycerides, was noted. These preliminary data do not support the use of L-carnitine for the rapid reversal of advanced fat tissue alterations due to HIV-associated lipodystrophy.

Body Weight↗
PubMed2001

HIV lipodystrophy: review of the syndrome and report of a case treated with liposuction.

BACKGROUND: A syndrome characterized by loss of fat on the face and limbs, localized fatty deposits on the trunk, and metabolic disturbances is becoming increasingly recognized in the human immunodeficiency virus (HIV) patient population. OBJECTIVE: To increase awareness of this syndrome among dermatologists and dermatologic surgeons and to review its various treatment options, including liposuction. METHODS: We present a patient with HIV lipodystrophy syndrome who underwent tumescent liposuction. We also describe our experience with liposuction in the management of this condition and review the treatment options that have been proposed in the literature. RESULTS: In the medical management of HIV lipodystrophy, various agents have been utilized but most have yielded disappointing results. Preliminary evidence on the use of tumescent liposuction in these patients suggests that significant improvement in the cosmetic disfigurement can be achieved. CONCLUSION: This syndrome is common among HIV-infected patients and remains difficult to treat. Although medical therapy may be preferable in most patients, liposuction represents a viable option in selected individuals.

Adult↗
PubMed2006

[Lipodystrophies related to antiretroviral treatment of HIV infection].

HIV infection requires the continuous administration of antiretroviral molecules. Individual molecules belonging to the two main classes, protease inhibitors (PIs) and nucleoside analogues inhibitors of the viral reverse transcriptase (NRTIs) have been shown to be involved in deleterious side effects collectively called the lipodystrophy syndrome. This syndrome associates altered body fat repartition (peripheral lipoatrophy and visceral fat hypertrophy) and metabolic alterations (dyslipidemia, insulin resistance and diabetes). The pathophysiology of these alterations is complex but different studies argue for adipose tissue being a target of some PIs and NRTIs acting through different mechanisms. NRTIs are able to induce mitochondrial dysfonction and to modify adipocyte phenotype and adipose tissue pattern of secretion of cytokines (TNFalpha, IL-6) and other adipokines (adiponectin, leptin) probably through the production of reactive oxygen species. Some PIs also act on adipocyte, alter its differentiation and insulin sensitivity and also the pattern of secretion of adipokines by adipose tissue. These hypotheses could explain the loss of adipose tissue, while the mechanisms of visceral fat hypertrophy remain speculative. Since some adipokines and the free fatty acids released by adipocytes play a major role in the control of liver and muscles insulin sensitivity, these alterations are probably involved in the metabolic alterations seen in the patients. In addition, lipodystrophic adipose tissue could be involved in the increased lesions of atherogenesis and steatohepatitis presented by these patients. The treatment of lipodystrophy remains difficult and, at present, privileges the switch of the more deleterious drugs towards new molecules less aggressive for adipose tissue.

Adipocytes↗
PubMed2003

Compensation by the muscle limits the metabolic consequences of lipodystrophy in PPAR gamma hypomorphic mice.

Peroxisome proliferator-activated receptor gamma (PPAR gamma) is a nuclear receptor, which controls adipocyte differentiation. We targeted with homologous recombination the PPAR gamma 2-specific exon B, resulting in a white adipose tissue knockdown of PPAR gamma. Although homozygous (PPAR gamma hyp/hyp) mice are born with similar weight as the WT mice, the PPAR gamma hyp/hyp animals become growth retarded and develop severe lipodystrophy and hyperlipidemia. Almost half of these PPAR gamma hyp/hyp mice die before adulthood, whereas the surviving PPAR gamma hyp/hyp animals overcome the growth retardation, yet remain lipodystrophic. In contrast to most lipodystrophic models, the adult PPAR gamma hyp/hyp mice only have mild glucose intolerance and do not have a fatty liver. These metabolic consequences of the lipodystrophy are relatively benign because of the induction of a compensatory gene expression program in the muscle that enables efficient oxidation of excess lipids. The PPAR gamma hyp/hyp mice unequivocally demonstrate that PPAR gamma is the master regulator of adipogenesis in vivo and establish that lipid and glucose homeostasis can be relatively well maintained in the absence of white adipose tissue.

Adipose Tissue↗
PubMed2000

HIV protease inhibitor-related lipodystrophy syndrome.

Human immunodeficiency virus (HIV) protease inhibitor (PI) therapy is frequently associated with a syndrome increasingly referred to as lipodystrophy syndrome, which is characterized by peripheral lipoatrophy, fat accumulation within the abdomen, in the breasts of women, and over the cervical vertebrae ("buffalo hump"), hyperlipidemia, and insulin resistance. In the largest study to date, peripheral lipoatrophy (an estimated 0.35-kg fat loss per month overall from the face, limbs, and upper trunk) was observed in association with all licensed PIs after a median 10 months of PI therapy. Diabetes mellitus type II appears to be a related, but less common, adverse effect. The lipodystrophy syndrome may be a result of the inhibition of 2 proteins involved in lipid metabolism that have significant homology to the catalytic site of HIV protease-namely, cytoplasmic retinoic acid binding protein type 1 and low density lipoprotein-receptor-related protein.

Catalytic Domain↗
PubMed2002

Exogenous cushing syndrome mimicking human immunodeficiency virus lipodystrophy.

A 45-year-old man infected with human immunodeficiency virus (HIV) developed abnormal fat accumulations that initially were believed to be caused by HIV lipodystrophy. Further clinical evaluation revealed, however, that the patient had developed exogenous Cushing syndrome, which presumably was caused by the inhibition of CYP3A4's metabolism of inhaled fluticasone by the protease inhibitor ritonavir. Clinicians should be aware that clinical clues may indicate conditions other than lipodystrophy that may cause abnormal fat accumulation and that fluticasone should be cautiously administered to patients who are receiving ritonavir.

Androstadienes↗
PubMed2002

Lipodystrophy syndrome and self-assessment of well-being and physical appearance in HIV-positive patients.

The lipodystrophy syndrome (LDS) is a growing problem in human immunodeficiency virus (HIV)-positive patients treated with highly active antiretroviral therapy (HAART). It is characterized by alterations of body composition and metabolic abnormalities. The goal of the study was to investigate attitudes toward health condition, well-being, and individual appearance in relation to LDS. Outpatients between July and October 2000 in an HIV-specialized unit at the University Hospital of Düsseldorf, Germany, underwent clinical evaluation and received a standardized written questionnaire. Of 389 patients eligible for analysis, 313 patients returned completed questionnaires (response rate, 80.5%). LDS was observed in 37.7%; the predominant manifestation was lipoatrophy of the face (32.9%). Individuals with and without LDS did not differ significantly in their attitude to the quality of their health condition and the amount of disturbance of their well-being by HIV infection. Participants with LDS felt recognizable as HIV-positive by physical appearance in 30.1%, compared to 18.3% in patients without LDS (p = 0.027). This difference became more pronounced after adjustment for gender, age, stage of disease, CD4 cell count, and duration of HAART (odds ratio, 2.04, 95%-confidence interval [CI] 1.09-3.84). In conclusion, LDS does not seem to disturb the general attitude toward health condition and well-being. However, patients presenting with lipodystrophy are about twice as likely to feel recognizable as HIV-positive by their physical appearance. LDS may thus be perceived as a characteristic mark of being HIV-positive by affected persons. A stigmatizing effect and social disadvantages may be the consequences.

Adult↗
PubMed2005

Lipodystrophy-associated symptoms and medication adherence in HIV/AIDS.

Lipodystrophy-associated manifestations remain a challenge for persons infected with HIV disease and their care providers. Symptomatic HIV disease and side effects of medications are implicated in antiretroviral medication nonadherence. This study examined the relationship between time since initial diagnosis with HIV, presence and type of lipodystrophic symptoms, and adherence to medication regimens in persons with HIV/AIDS. Using a cross-sectional, descriptive design, the sample was composed of 165 persons from three outpatient HIV settings in Boston, Massachusetts; Fresno, California; and Victoria, Texas. Participants completed a questionnaire comprised of sociodemographic questions, adherence scales, quality-of-life scales, and open-ended questions regarding presence and types of lipodystrophy-associated symptoms, and how these physical changes made them feel. Adherence was moderate with a mean score of 1.44 (standard deviation [SD] +/- 1.33) on the Morisky Medication Adherence Scale (MMAS). The MMAS is a Likert-type scale ranging from 0-4, with "0" indicating very adherent. This finding indicated that the participants took their medications moderately well despite self-reports of significant numbers of HIV disease and treatment-related body fat changes. Time since initial diagnosis was 8.86 +/- 5.55 years and was not related to adherence. Nor did the type of lipodystrophic symptoms affect adherence. Quality of life however, was significantly related to adherence suggesting an approach that might be taken to improve adherence.

Adult↗
PubMed1997

Dunnigan-Kobberling syndrome: an autosomal dominant form of partial lipodystrophy.

Dunnigan-Kobberling syndrome is a form of partial lipodystrophy characterized by sparing of the face. Despite descriptions of six families since 1974, details of total body adipose tissue distribution and studies of carbohydrate and fat metabolism are lacking. The mode of inheritance also remains unclear, with most authors favouring an X-linked dominant transmission lethal in the hemizygous male. We examined 23 members of a family, of whom at least eight had partial lipodystrophy. Auxological evaluation and cross-sectional imaging showed absence of subcutaneous fat, presence of adipose tissue inside the body cavities, and skeletal muscle hypertrophy. Biochemical evaluation identified insulin resistance but revealed inadequate suppression of non-esterified fatty acids. In this family, male-to-male transmission supports an autosomal dominant mode of inheritance for Dunnigan-Kobberling syndrome.

Acanthosis Nigricans↗
PubMed1994

Facial contour reconstruction in lipodystrophy using a double paddle dermis-fat radial forearm free flap.

Facial lipodystrophy is a relatively rare disease and very little has been reported concerning the reconstruction of this facial deformity compared with Romberg's disease. In this article we report a new surgical procedure using a double paddle radial forearm dermis--fat free flap. By using this unique flap, we could reconstruct soft tissue defects on both cheeks in a one-stage operation using one flap. In the previous conventional procedure, two flaps are required for the reconstruction of bilateral defects on the face. Therefore, we also made a comparison between our flap and the conventional flap with regard to their advantages and disadvantages. Although this is a limited experience, we think using this flap is a preferable method of treating facial lipodystrophy.

Adult↗
PubMed2005

Use of recombinant human growth hormone in HIV-associated lipodystrophy.

PURPOSE OF REVIEW: In the past few years there has been great interest in potential interventions for the body shape abnormalities in HIV-infected individuals that have been termed the HIV-associated lipodystrophy syndrome. This review examines the studies that have focused on the effects of recombinant human growth hormone as a treatment for the central fat accumulation that is part of this syndrome. RECENT FINDINGS: A recent placebo-controlled trial confirmed that growth hormone leads to a significant dose-dependent improvement in trunk or visceral fat. These improvements were accompanied by dose-dependent side-effects, including glucose intolerance/insulin resistance and tissue edema. With the improvements seen with growth hormone treatment, the patient's body image and sense of well-being also improved. Recent novel data suggest that the use of growth hormone-releasing hormone may possibly be an alternative to treating HIV lipodystrophy with recombinant human growth hormone, because it appears to have fewer adverse events and results in the same benefits in HIV-infected patients with central fat deposition. SUMMARY: Growth hormone has been shown to lead to a dose-dependent improvement in patients with HIV-associated visceral fat accumulation. Treatment with growth hormone has been complicated by predictable and dose-dependent side-effects. The optimal dose and duration of treatment with growth hormone is not known.

Drug Therapy, Combination↗
PubMed2001

Mitochondrial involvement in antiretroviral therapy-related lipodystrophy.

OBJECTIVES: The management of HIV infection has greatly improved during recent years essentially because of the appearance of new antiretroviral drugs. Highly active antiretroviral therapy (HAART) has achieved important reductions of viraemia and significant recoveries of CD4(+) cell counts in HIV-infected patients. Nonetheless, cases of HIV-infected individuals experiencing lipodystrophy (LD) are being increasingly reported. The purpose of this work was to analyse whether the presence of mitochondrial abnormalities is a frequent feature in LD, since we previously detected mitochondrial abnormalities in an HIV-patient. The second main objective was to study whether LD could be associated with a specific drug. DESIGN: Seven HIV patients presenting LD and five HIV non-LD controls participated in the study. LD patients met the following criteria: (1) LD was their only clinical abnormality, (2) LD was clinically relevant, (3) compliance with antiretroviral treatment was higher than 90% and (4) patients did not have personal or familial history suggestive of mitochondrial disease or neuromuscular disorder. METHODS: Histological stainings, histo-enzymatic reactions, enzymatic and respiratory activities of mitochondrial respiratory chain complexes, and mitochondrial DNA (mtDNA) depletion and rearrangements were examined on muscle mitochondria. RESULTS: Structural muscle abnormalities, mitochondrial respiratory chain dysfunction or mtDNA deletions were detected in all HIV lipodystrophic patients. CONCLUSIONS: The mitochondrial abnormalities found suggest that mitochondrial dysfunction could play a role in the development of antiretroviral therapy-related lipodystrophy.

Adult↗
PubMed2001

Elevated blood pressure in subjects with lipodystrophy.

OBJECTIVES: To assess the prevalence of elevated blood pressure in patients with lipodystrophy. DESIGN: Case-control study. PARTICIPANTS: Forty-two patients with abnormal body fat (100%) and serum lipids (86%) (HIV-positive cohort) were matched by age and sex to 42 HIV-positive controls without previously diagnosed lipodystrophy and to 13 HIV-negative controls. SETTING: Tertiary care, university-based, fully dedicated HIV clinic. MAIN OUTCOME MEASURES: Frequency and magnitude of elevated blood pressure during highly active antiretroviral therapy. RESULTS: There were 23 +/- 16 and 22 +/- 12 blood pressure measurements recorded per subject over 21 +/- 11 and 22 +/- 11 months for the HIV-positive cohort and HIV-positive controls, respectively. Three or more elevated readings occurred in 74% of the cohort and in 48% of the HIV-positive controls (P = 0.01) and accounted for 38 +/- 25% versus 22 +/- 26% (P = 0.01) of the total readings, respectively. The average of the three highest systolic readings (153 +/- 17 versus 144 +/- 15 mmHg; P = 0.01) and diastolic readings (92 +/- 10 versus 87 +/- 9 mmHg; P = 0.01) was greater for the cohort than for the HIV-positive controls. Family history of hypertension was more common in the cohort than in the controls but accounted for only 13% of the log odds ratio value for elevated blood pressure in the cohort. Systolic blood pressure was correlated with waist-to-hip ratios in the cohort (r = 0.45; P = 0.003) but not in the HIV controls (r = 0.06; P = 0.68) and tended to be related to fasting triglycerides (r = 0.34; P = 0.052) in subjects with HIV. CONCLUSIONS: Elevated blood pressure may be linked to the metabolic disorders occurring in patients with HIV, as in the dysmetabolic syndrome.

Adipose Tissue↗
PubMed2001

Highly active antiretroviral-treated HIV-infected children show fat distribution changes even in absence of lipodystrophy.

BACKGROUND: Combined use of dual-energy X-ray absorptiometry (DXA) and magnetic resonance imaging (MRI) allows a precise estimate of regional body composition and intra-abdominal adipose tissue (IAT). Data on body composition in HIV-infected children (HIV+) receiving highly active antiretroviral therapy (HAART) with (LD+) and without (LD-) lipodystrophy are lacking. METHODS: DXA scans were performed in 34 HIV+: six LD+, 28 LD- and 34 pair-matched (age, sex and body mass index) healthy controls (HC): six for LD+ (HC+) and 28 for LD- (HC-). MRI scans were performed in 16 HIV+: six LD+, 10 LD- and 16 pair-matched (age and sex) HC. Data were analysed by analysis of variance, post hoc Fisher test and Mann-Whitney test. RESULTS: LD+ and LD- were similar for: previous exposure to zidovudine/zidovudine + didanosine, months on HAART (stavudine + lamuvidine + one protease inhibitor), CD4+ cells, patients with HIV-RNA < 50 copies/ml. In HIV+ and HC, fat mass and distribution were significantly different, whereas lean mass was comparable. Thus, LD+ and LD- as compared to HC+ and HC- respectively showed: (1) reduced fat amount and percentage; (2) lower truncal fat mass; (3) markedly reduced limbs fat mass. Within the HIV+ group, (4) LD+ showed higher fat trunk/fat total (P = 0.04) and lower fat limbs/ fat total ratios (P = 0.009) than LD-; (5) LD+ showed larger IAT areas than LD- and HC (P < 0.0003). CONCLUSIONS: Increased central fat and peripheral lipoatrophy are distinctive features of all HAART-treated children. Changes in body fat composition are detectable by DXA even in the absence of signs of Lipodystrophy. Only LD+ show true central obesity.

Absorptiometry, Photon↗
PubMed2001

Failure to maintain long-term adherence to highly active antiretroviral therapy: the role of lipodystrophy.

In a sample of 277 patients included in the French APROCO cohort study who were initially adherent at follow-up visit 4 months after initiation of a protease inhibitor-containing regimen, 76.4% self-reported at least one lipodystrophy-related symptom and 30.0% failed to maintain adherence behaviour 20 months after enrolment. After multiple adjustment for other related factors, such as younger age, alcohol consumption and poor housing conditions, the number of self-reported lipodystrophy symptoms was independently associated with adherence failure.

Adult↗
PubMed2002

Skeletal muscle mitochondrial function and exercise capacity in HIV-infected patients with lipodystrophy and elevated p-lactate levels.

OBJECTIVE: To investigate the skeletal muscle mitochondrial function in HIV-infected patients with lipodystrophy or elevated p-lactate levels. DESIGN: Eight HIV patients treated with highly active antiretroviral therapy, with lipodystrophy or elevated p-lactate, and eight healthy controls were exposed to incremental exercise until exhaustion. METHODS: Blood samples and gas analysis were performed at rest, during exercise and in recovery. Oxygen consumption, workload and blood lactate were assessed. Before and immediately after exercise muscle biopsies were obtained, in which citrate synthase (CS), hydroxyacyl-coenzyme A dehydrogenase (HD), glycogen and nucleotides were measured. RESULTS: Maximal workload was significantly lower in patients compared with controls [171 Watt (88-206) versus 235 Watt (118-294) P = 0.05]. A trend towards lower maximal oxygen consumption (VO(2max)) was detected in patients [2136 ml/min (1221-2598) versus 2985 ml/min (1506-3959) P = 0.11]. Patients had significantly elevated levels of blood lactate at rest [1.55 mmol/l (1-2.5) versus 0.8 mmo/l (0.37-1.1) P < 0.01), but no significant difference in maximal blood-lactate values was found. The decline in blood lactate in the recovery period was similar between groups. There was no significant difference in CS, HD, glycogen or nucleotides. CONCLUSION: The significantly lower working capacity and the trend towards reduced VO(2max) in patients could be caused by mitochondrial dysfunction, but may also be caused by impaired physical fitness. The similar levels of nucleotides, CS, HD, and glycogen and the normal increase in blood lactate during exercise indicates a normal oxidative phosphorylation. No evidence of serious damage to skeletal muscle mitochondrial function was found.

3-Hydroxyacyl CoA Dehydrogenases↗
PubMed2002

Reversal of atherogenic lipoprotein profile in HIV-1 infected patients with lipodystrophy after replacing protease inhibitors by nevirapine.

BACKGROUND: The widespread use of protease inhibitors (PI) has been associated with abnormalities in the lipid profile of HIV-1-infected patients. Treatment simplification approaches in which PI are replaced by nevirapine (NVP) have been shown to improve PI-related toxicity. OBJECTIVE: To assess the impact on plasma lipids of replacing the PI by NVP in HIV-1 infected patients with lipodystrophy. METHODS: We studied 34 patients with lipodystrophy who had been the first to be enrolled in a prospective, randomized trial of continuing current treatment, or replacing PI with NVP. Sixteen patients replaced their PI with NVP and 18 continued their current PI-containing treatment. Total, low density lipoprotein (LDL), very low density lipoprotein (VLDL), intermediate density lipoprotein and high density lipoprotein (HDL) cholesterol and triglyceride levels, the size and particle number of LDL were determined at baseline and after 24 weeks, by nucleic magnetic resonance spectroscopy. FINDINGS: After 24 weeks of replacing the PI with NVP, we observed a reduction of total cholesterol (P = 0.028), LDL-cholesterol (P = 0.001), the number of circulating LDL particles (P = 0.003) and the VLDL-1 triglyceride level (P = 0.032). A concomitant significant increase was observed in both HDL-cholesterol level (P = 0.002) and HDL particle size (P < 0.001). No significant changes were observed in the group that continued taking the PI. CONCLUSIONS: The replacement of PI by NVP improved the lipid profile both by reducing the number and lipid content of atherogenic LDL particles, and increasing the protective HDL fraction. Although total triglyceride levels remained unchanged, a reduction in the VLDL-1 fraction contributes to the reduction of LDL particles. These changes are expected to reduce the risk of cardiovascular disease in HIV-1-infected patients on highly active antiretroviral therapy.

Adult↗