Lipodystrophy In HIV-infected Patients Research Articles

Correlation of APOE polymorphism, expression, and plasma levels with cardiac comorbidities among lipodystrophy in HIV-infected patients

Lipodystrophy in HIV-infected patients (LDHIV) includes morphological and metabolic abnormalities, including lipid and glucose metabolism. ApoE plays a role in the transport and clearance of lipoprotein. In the general population, ApoE 112 (rs429358) and 158 (rs7412) polymorphisms were linked to severe dyslipidemia. Therefore, we investigated ApoE polymorphism using PCR-RFLP in 200 HIV patients (100 with HIV-associated lipodystrophy (HIVLD), 100 without HIVLD), as well as 100 healthy controls. We also assessed ApoE expression using qRT-PCR and measured its level using ELISA. The APOE 4/4, 3/4, and 2/4 genotypes have been associated with a decreased risk of HIV-1 infection. (P = 0.0001, OR = 0.18; P = 0.006, OR = 0.87; P = 0.006, OR = 0.09) when compared between HIV-positive individuals and healthy controls. Conversely, APOE allele 2 was linked to a higher risk of acquiring HIV-1 (P = 0.03, OR = 3.02). APOE allele 2 was linked to a higher likelihood of HIVLD severity when compared between patients with and without HIVLD (P = 0.05, OR = 2.82). When comparing patients with HIVLD to healthy controls, the APOE 4/4 and 2/4 genotypes as well as allele 4 were linked with the reduced risk of LDHIV (P = 0.0006, OR = 0.21; P = 0.01, OR = 0.18; P = 0.0002, OR = 0.40). When compared to patients without HIVLD from healthy controls, the ApoE 4/4 genotype, 2 and 4 alleles, were linked to a reduced risk of developing HIVLD (P = 0.0009, OR = 0.14; P = 0.0001, OR = 0.17; P = 0.00001, OR = 0.39). When comparing impaired to normal cholesterol levels in patients without HIVLD, the ApoE 3/4 genotype was linked with the increased risk of impaired cholesterol levels (P = 0.02, OR = 3.37). When comparing impaired and normal glucose levels in patients without HIVLD, the ApoE 4/4 genotype was associated to an elevated risk of impaired glucose levels (P = 0.03, OR = 8.27). In multivariate analysis, independent impaired cholesterol, LDL, and glucose levels were associated with a higher risk of lipodystrophy severity (P = 0.04, OR = 2.33; P = 0.001, OR = 4.05; P = 0.05, OR = 2.63). ApoE expression was up-regulated in LDHIV with a fold change value of 4.02 compared to those without HIVLD. ApoE protein level was found to be higher in patients of the HIVLD group (3.01 mg/dL) compared to those without HIVLD group (2.83 mg/dL). In conclusion, individuals with ApoE allele 2 were at higher risk for HIV-1 acquisition and severity of HIVLD, whereas those with ApoE allele 4 were at reduced HIVLD severity and development risk. It’s possible that ApoE’s increased level and its overexpression are related to the ApoE allele 2 in HIVLD patients. The development of LDHIV may be facilitated by the APOE 3/4 and 4/4 genotypes as well as abnormal glucose and cholesterol levels.

PP188-SUN: Lipodystrophy in HIV Infected Patients – A Question Still to Address in Current Times?

Circumference (MUAC), Triceps Skinfold Thickness (TSF), Mid Arm Muscle Circumference (MAMC), Albumin, Transferrin, Cholesterol. BMI, TSF, MAMC, biochemical parameters a Nutritional and Prognostic Score ranging 0 6 was created. Results: 234 patients, (39 94 years). Cancers: larynx (79), oral cavity (72), pharynx (43), proximal oesophagus (26) and other tissues (14). 149 patients died, 33 still in the Artificial Nutrition Outpatients Consultation, 36 resume oral feeding. NRS 2002 3 and caloric needs under 50% showed in all patients. IMC (12.7 43); 189, 197 and 168 displayed a low, respectively, MUAC, TSF and MAMC. Laboratory values with 91, 155 and 119 patients displayed a low, respectively, albumin, transferrin and cholesterol. Nutritional and Prognostic Score showed that lower scores are associated with lower survival rates (p = 0.029). Conclusion: HNC patients are malnourished when are referred to PEG. All presented malnourished according NRS-2002 and dietary assessment, and most of them presented malnourished according anthropometric and laboratory data. Nutritional and Prognostic score 3 show worst outcome and lower survival, needing special clinical and nutritional support.

Relationship of oxidative stress and chronic proinflammatory state with the development of metabolic syndrome and lipodystrophy in hiv infected patients

Relationship of oxidative stress and chronic proinflammatory state with the development of metabolic syndrome and lipodystrophy in hiv infected patients

Prevalence of HIV-Associated Lipodystrophy in Brazil: A Systematic Review of the Literature

Background: Currently, AIDS is considered a chronic, treatable disease for those who have access to Highly Active Antiretroviral Therapy (HAART). However, the decline in morbidity and mortality rates with an increase in life expectancy attributable to drug treatment has adverse effects associated with its continued use, such as changes in the body-fat distribution and metabolic abnormalities that define lipodystrophy syndrome. Objective: To conduct a systematic review of the prevalence of and methods used for defining and grading lipodystrophy in individuals living with HIV in Brazil. Methods: The electronic search was performed in Medline, Lilacs, SciELO, and thesis and dissertation databases. Original observational studies that had determined the prevalence of lipodystrophy in HIV-infected patients were included. Results: 103 articles were retrieved, and 16 were included in this review. The prevalence of lipodystrophy ranged between 32.4% and 88.6%. The methods used to assess lipodystrophy were: (i) Patient self-report and physician examination; (ii) patient self-report alone; (iii) physician examination and anthropometric measurements; (iv) patient self-report and anthropometric measurements; and (v) physician examination alone. Conclusion: The weighted average prevalence of lipodystrophy was 53.5%, and the most commonly used method to assess lipodystrophy was the patient self-report and physician examination. Further longitudinal and diagnostic studies should be conducted to determine the incidence and accuracy of lipodystrophy.

Exploring the pathophysiology behind the more common genetic and acquired lipodystrophies

Lipodystrophies are an immense group of genetic or acquired metabolic disorders that are characterized by varying degrees of body fat loss and in some instances localized accumulation of subcutaneous fat. Lipodystrophies are often tightly linked with profound metabolic complications; this strong bond emphasizes and reinforces the significance of adipose tissue as a dynamic endocrine organ. The extent of fat loss determines the severity of associated metabolic complications such as diabetes mellitus, hypertriglyceridemia and hepatic steatosis. The lipodystrophies can be divided into generalized, partial or local, depending on the degree and locality of the observable fat loss; moreover, the generalized and partial divisions can be partitioned further into inherited or acquired forms. The major genetic factors in the generalized forms of the lipodystrophies, particularly Congenital generalized lipodystrophy (CGL)-Berardinelli-Seip syndrome, are the AGPAT2, BSCL2, caveolin 1 (CAV1) and polymerase-I-and-transcriptrelease factor (PTRF) genes. In the acquired forms, genes such as LMNA, PPARG, CIDEC (cell-death-inducing DNA fragmentation factor a-like effector c) and PLIN1 are heavily involved in familial partial lipodystrophy (FPLD) type 2 (also known as the Dunnigan-Variety) and WRN along with RECQL5 in Werner Syndrome (WS). Autoimmune causes are particularly noted in acquired partial lipodystrophy (APL)-Barraquer-Simons syndrome and in AGL-Lawrence syndrome; panniculitis has been shown to have a substantial role in the former as well as in other forms of localized lipodystrophies. Patients with human immunodeficiency virus (HIV) exposed to protease inhibitors, nucleoside reverse transcriptase inhibitors (NRTIs) (for example, zidovudine and stavudine) or non-nucleoside reverse transcriptase inhibitors (NNRTIs) (for example, efavirenz) while undergoing Highly Active Antiretroviral Therapy (HAART) have led to the current most-prevalent form of the lipodystrophies: lipodystrophy in HIV-infected patients (LD-HIV) and HAART-associated lipodystrophy syndrome (HALS).

Small-Dense LDL Cholesterol/Large-Buoyant LDL Cholesterol Ratio as an Excellent Marker for Indicating Lipodystrophy in HIV-Infected Patients

To examine whether the lipid parameters are predicting factors for human immunodeficiency virus (HIV)-associated lipodystrophy. Whole-body fat compositions of HIV-positive patients receiving stavudine-containing antiretroviral regimens (n = 79) were determined. Lipodystrophy was defined as a ratio of trunk fat mass/lower limb fat mass greater than 2.28. Blood samples were analyzed for total cholesterol (TC), triglycerides, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), small-dense LDL-C (sdLDL-C), apoAI, apoB, lipoprotein(a), and CD4 cell counts. Large-buoyant LDL-C (lbLDL-C) was calculated (LDL-C minus sdLDL-C). Twenty-six patients were classified as having lipodystrophy. The mean values of triglycerides, HDL-C, sdLDL-C, apoB, TC/HDL-C, apolipoprotein (apo) B/apoAI, and sdLDL-C/lbLDL-C showed significant differences between patients with and without lipodystrophy (P < .02). Using logistic regression analysis, sdLDL-C/lbLDL-C was identified as a significant predictor of lipodystrophy (P < .001). At a ratio of 0.554, the odds ratio was 17.8 with a likelihood ratio of 5.5. The sdLDL-C/lbLDL-C ratio is an excellent marker for indicating lipodystrophy in HIV-infected patients.

Polymorphisms of Pyrimidine Pathway Enzymes Encoding Genes and HLA-B*40∶01 Carriage in Stavudine-Associated Lipodystrophy in HIV-Infected Patients

PurposeTo assess in a cohort of Caucasian patients exposed to stavudine (d4T) the association of polymorphisms in pyrimidine pathway enzymes and HLA-B*40∶01 carriage with HIV/Highly active antiretroviral therapy (HAART)-associated lipodystrophy syndrome (HALS).MethodsThree-hundred and thirty-six patients, 187 with HALS and 149 without HALS, and 72 uninfected subjects were recruited. The diagnosis of HALS was performed following the criteria of the Lipodystrophy Severity Grading Scale. Polymorphisms in the thymidylate synthase (TS) and methylene-tetrahydrofolate reductase (MTHFR) genes were determined by direct sequencing, HLA-B genotyping by PCR-SSOr Luminex Technology, and intracellular levels of stavudine triphosphate (d4T-TP) by a LC-MS/MS assay method.ResultsHALS was associated with the presence of a low expression TS genotype polymorphism (64.7% vs. 42.9%, OR = 2.43; 95%CI: 1.53–3.88, P<0.0001). MTHFR gene polymorphisms and HLA-B*40∶01 carriage were not associated with HALS or d4T-TP intracellular levels. Low and high expression TS polymorphisms had different d4T-TP intracellular levels (25.60 vs. 13.60 fmol/106 cells, P<0.0001). Independent factors associated with HALS were(OR [95%CI]: (a) Combined TS and MTHFR genotypes (p = 0.006, reference category (ref.): ‘A+A’; OR for ‘A+B’ vs. ref.: 1.39 [0.69–2.80]; OR for ‘B+A’ vs. ref.: 2.16 [1.22–3.83]; OR for ‘B+B’ vs. ref.: 3.13, 95%CI: 1.54–6.35), (b) maximum viral load ≥5 log10 (OR: 2.55, 95%CI: 1.56–4.14, P = 0.001), (c) use of EFV (1.10 [1.00–1.21], P = 0.008, per year of use).ConclusionHALS is associated with combined low-expression TS and MTHFR associated with high activity polymorphisms but not with HLA-B*40∶01 carriage in Caucasian patients with long-term exposure to stavudine.

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.

Polymorphisms inFasGene Is Associated with HIV-Related Lipoatrophy in Thai Patients

The present study aimed to evaluate the role of genetic polymorphisms in the emergence of lipoatrophy or lipodystrophy in HIV-infected patients with antiretroviral therapy (ART) in Thailand. Position 455 upstream of the Apolipoprotein C3 gene (ApoC3 T-455C, rs2854116), codon 64 of the Beta3 adrenergic receptor gene (ARβ3 Tcod64C, rs4994), and position 670 upstream of the Fas gene (Fas A-670G, rs1800682) were genotyped in 829 HIV-infected Thai patients who had started ART. Crude and adjusted incidence rate ratios (IRR) were calculated using Poisson regression. The serum levels of cholesterol, triglycerides, high-density lipoprotein (HDL), and low-density lipoprotein (LDL) were also analyzed. Multivariate analysis revealed an association between the Fas -670AA genotype, but not the ApoC3 -455 or ARβ3 cod64 genotypes, with the incidence of lipoatrophy after adjusting for gender and stavudine (d4T)-containing regimens (IRR=1.72, 95% CI=1.20-2.45, p=0.003). However, ApoC3 -455C homozygous patients showed elevated serum levels of triglycerides, while this genotype did not affect serum total cholesterol, HDL, or LDL levels in patients with lipoatrophy or lipodystrophy. In contrast, the ARβ3 cod64 genotype did not show any significant association with the serum levels of cholesterol, triglycerides, HDL, or LDL. In conclusion, Fas -670AA affected the incidence of lipoatrophy in HIV-1-infected Thai patients, while the ApoC3 -455C allele affected the serum levels of triglycerides. These results confirmed the role of genetics in the development of ART-related metabolic disorders.

Mitochondrial DNA Haplogroups and Incidence of Lipodystrophy in HIV-Infected Patients on Long-Term Antiretroviral Therapy

We investigated the rates of lipodystrophy events, according to mitochondrial DNA haplogroup, in 187 patients starting combination antiretroviral therapy and following it. Incidence rates of lipoatrophy and fat accumulation were 8.2 and 4.8 per 100 person-years of follow-up, respectively. In multivariable models, patients with haplogroup K were at higher risk of any lipodystrophy [adjusted relative risk (aRR) 4.02, P = 0.0009], lipoatrophy (competing-risk aRR 2.42, P = 0.09; cause-specific aRR 2.99, P = 0.031), and fat accumulation (competing-risk aRR, 2.63, P = 0.11; cause-specific aRR 5.27, P = 0.019) than those with haplogroup H. Mitochondrial haplogroups may explain part of the genetic predisposition to lipodystrophy during combination antiretroviral therapy.

Mitochondrial DNA haplogroups and incidence of lipodystrophy in HIV-infected patients on long-term antiretroviral therapy

Mitochondrial DNA haplogroups and incidence of lipodystrophy in HIV-infected patients on long-term antiretroviral therapy

SP2-9 Diagnostic criteria of lipodystrophy in HIV-infected patients

IntroductionThe prevalence of lipodystrophy ranges from 2 to 84% and the range of findings stems from differences between the populations studied and lack of standardised diagnostic criteria. The diagnosis of...

New and emerging agents in the management of lipodystrophy in HIV-infected patients

Lipodystrophy remains a major long-term complication in human immunodeficiency virus-infected patients under antiretroviral (ARV) therapy. Patients may present with lipoatrophy or lipohypertrophy or both. The choice of treatments to improve fat redistribution depends on the form of lipodystrophy and its duration. Measures known to improve lipoatrophy are switches in ARV therapy (stavudine or zidovudine to abacavir or tenofovir) and filling interventions. Pioglitazone may be added to these measures, although any benefits appear small. Uridine and leptin were found to be disappointing so far. Regarding lipohypertrophy, diet and exercise, recombinant human growth hormone, and metformin may reduce visceral fat, but may worsen subcutaneous lipoatrophy. Surgical therapy may be required. Attractive pharmacologic treatments include growth hormone-releasing factor and leptin. Adiponectin and adiponectin receptors are promising therapeutic targets to explore.

FABP4 plasma levels are increased in familial combined hyperlipidemia

FABP4 plasma levels are increased in familial combined hyperlipidemia

Fat Mass Ratio: An Objective Tool to Define Lipodystrophy in HIV-Infected Patients Under Antiretroviral Therapy

Human immunodeficiency virus (HIV) infection and its treatment with antiretroviral therapy (ART) have been associated with lipodystrophy. Different clinical methodologies have been used to define the syndrome. The aim of this study was to propose gender-specific reference values using objective measurements for defining lipodystrophy in HIV-infected patients. Using dual-energy X-ray absorptiometry (DXA), total body composition was analyzed in 221 HIV-infected patients under ART (146 men). We used fat mass ratio (FMR) as the ratio between the percent of the trunk fat mass and the percent of the lower-limb fat mass. One hundred forty patients (63.6%) presented clinically defined lipodystrophy. In men, the optimal cutoff value for the FMR was 1.961 (area under the receiver operating characteristic curve [AUC]: 0.74 [95% confidence interval (CI): 0.66–0.82], p < 0.001), with a sensitivity 58.3%, a specificity 83.7%, a positive predictive value (PPV) of 89.6% and a negative predictive value (NPV) of 45.5%. In women, the optimal cutoff value for the FMR was 1.329 (AUC: 0.74 [95% CI: 0.63–0.86], p < 0.001), with a sensitivity 51.4%, a specificity 94.6%, a PPV of 90.5%, and an NPV of 66.0%. The FMR evaluated by DXA with the gender-specific cutoffs defined here is an objective way to define HIV-related lipodystrophy.

Association betweenHLA‐B*4001and Lipodystrophy among HIV‐Infected Patients from Thailand Who Received a Stavudine‐Containing Antiretroviral Regimen

Stavudine-containing antiretroviral regimens are widely used in developing countries. Stavudine-associated lipodystrophy commonly occurs, without a clear predictable pattern owing to the unknown interaction between stavudine and the host, among patients who received this regimen. The aim of this study was to determine the clinical risk factors and human leukocyte antigen (HLA) alleles associated with stavudine-associated lipodystrophy. A case-control, cross-sectional study was conducted for HIV-infected patients receiving stavudine-containing antiretroviral regimens. Clinical assessments for lipodystrophy by physical examination, anthropometry, and dual-energy X-ray absorptiometry were obtained. On the basis of their clinical assessment, the patients were classified into 2 groups: the case group (moderated to severe lipodystrophy) and the control group (absent to mild lipodystrophy). The clinical characteristics and allelic distribution of HLA-A, HLA-B, HLA-C, HLA-DRB1, HLA-DQB1, and HLA-DPB1 were compared between the case group and the control group, to determine the possible association with stavudine-associated lipodystrophy. There were 103 patients; 55 patients were in the case group, and 48 patients were in the control group. By use of forward stepwise logistic regression, the presence of HLA-B*4001 (odds ratio [OR], 14.05; 95% confidence interval [CI], 2.57-76.59; P=.002) and a longer duration of stavudine treatment (OR, 1.02; 95% CI, 1.00-1.04; P=.02) were significantly associated with stavudine-associated lipodystrophy, whereas a higher body mass index during treatment (OR, 0.73; 95% CI, 0.61-0.86; P<.001) was associated with a lower risk for lipodystrophy. HLA-B*4001 has a high specificity (95.8%) and a positive predictive value (88.9%) for lipodystrophy. HLA-B*4001 is a strong genetic risk factor for stavudine-associated lipodystrophy in HIV-infected patients in Thailand. HLA-B*4001 may be used as a genetic marker to predict which patients will develop stavudine-associated lipodystrophy, to avoid or shorten the duration of stavudine use. This finding needs to be confirmed in further replication studies.

Disturbance of Apolipoprotein B100 Containing Lipoprotein Metabolism in Severe Hyperlipidemic and Lipodystrophic HIV Patients on Combined Antiretroviral Therapy: Evidences of Insulin Resistance Effect

The aim was to study the mechanisms involved in the dyslipidemia associated with lipodystrophy in HIV infected patients on antiretroviral therapy (ART). We investigated the in vivo kinetics of apolipoprotein B100 (apoB) containing lipoproteins using a 14 h primed constant infusion of [5,5,5, (2)H(3)] leucine and compartmental modelling in normolipidemic without lipodystrophy (7 patients, NLD) or dyslipidemic with lipodystrophy (7 patients, LD) treated with ART. Subjects in group LD showed higher plasma triglycerides (5.73+/-3.58 vs 1.29+/-0.54 g/L, p<0.005), total cholesterol (2.98+/-0.95 vs 1.74+/-0.26 g/L, p<0.05), apoB (1.49+/-1.11 vs 0.51+/-0.11 g/L, p<0.005) and apolipoprotein CIII in apoB containing lipoproteins (117.7+/-42.2 vs 22.6+/-23.9 g/L, p<0.005). LD subjects exhibited an insulin resistant as observed by higher HOMA (3.44+/-1.62 vs 1.60+/-0.61, p<0.05). They exhibited an increase in VLDL (1.24+/-0.33 vs 0.80+/-0.21 mg/kg/h, p<0.05), decrease in IDL (0.20+/-0.10 vs 0.48+/-0.24 mg/kg/h, p<0.05) and no difference in LDL (0.38+/-0.19 vs 0.45+/-0.25 mg/kg/h) production rate. LD subject also showed a dramatic decrease in transformation of VLDL to IDL (0.013+/-0.010 vs 0.258+/-0.206 h(-1), p<0.005) and IDL to LDL (0.088+/-0.093 vs 0.366+/-0.189 h(-1), p<0.05) and a decrease in fractional catabolic rate (FCR) of VLDL (0.199+/-0.132 vs 0.555+/-0.398 h(-1), p<0.05), IDL (0.110+/-0.08 vs 0.523+/-0.275 h(-1), p<0.05) and LDL (0.010+/-0.005 vs 0.025+/-0.014 h(-1), p<0.05). These disturbances, overproduction and an overall delayed catabolism of apoB, are similar to those observed using the same protocol in insulin resistant subjects. Our study suggests that metabolic disturbance of apoB100 observed in lipodystrophic HIV in combined antiretroviral therapy are consecutive to insulin resistance induced by the treatment.

Ultrasonographic assessment of lipodystrophy in HIV-1-infected patients

We performed a cross-sectional study of physical changes in HIV-infected adults to evaluate the role of ultrasonography for the diagnosis of lipodystrophy. Sixty HIV-infected patients were recruited from 1 June to 31 December 2006. A total of 34 patients were included in the lipodystrophy group and 26 in no lipodystrophy group. Thickness of subcutaneous fat was measured twice with a high-frequency (15 MHz) transducer by transverse scans at four skin-based reference points: the periumbilical region, the brachial region, the crural region and the malar region. Visceral fat thickness was determined with a low-frequency (3.75 MHz) transducer at two skin reference points: perirenal fat diameter and visceral abdominal fat. Compared with HIV-infected patients without lipodystrophy, those with lipoatrophy or mixed lipodystrophy had thinner facial, arm and leg fat, whereas patients with lipodystrophy showed thicker intra-abdominal fat. The median of the ratio between intra-abdominal fat and subcutaneous fat and between perirenal fat diameter and body mass index in the lipodystrophy group was higher than in the no lipodystrophy group. The measurements of brachial, malar and crural fat were significantly lower in patients with lipodystrophy. We consider the ratio between visceral adipose tissue and subcutaneous adipose tissue and the thickness of malar fat to be the most useful ultrasonographic parameters for the early diagnosis of lipodystrophy in HIV-infected patients on highly active antiretroviral therapy.

Prevalência da lipodistrofia associada ao HIV em pacientes ambulatoriais brasileiros: relação com síndrome metabólica e fatores de risco cardiovascular

Lipodystrophy in HIV-infected patients (LDHIV) affects 40-50% of HIV-infected patients, but there are no data on its prevalence in Brazil. The aim of this study was to assess the LDHIV prevalence among HIV-infected adult Brazilian individuals, as well as to evaluate LDHIV association with cardiovascular risk factors and the metabolic syndrome (MS). It was included 180 adult HIV-infected outpatients consecutively seen in the Infectology Clinic of Universidade Estadual de Londrina. Anthropometric and clinical data (blood pressure, family and personal comorbidities, duration of HIV infection/AIDS, antiretroviral drugs used, CD4+ cells, viral load, fasting glycemia and plasma lipids) were obtained both from a clinical interview as well as from medical charts. LDHIV was defined as the presence of body changes self-reported by the patients and confirmed by clinical exam. MS was defined using the NCEP-ATPIII criteria, reviewed and modified by AHA/NHLBI. A 55% prevalence of LDHIV was found. Individuals with LDHIV presented a longer infected period since HIV infection, longer AIDS duration and longer use of antiretroviral drugs. In multivariate analysis, women (p=0.006) and AIDS duration >8 years (p<0.001) were independently associated with LDHIV. Concerning MS diagnostic criteria, high blood pressure was found in 32%, low HDL-cholesterol in 68%, hypertriglyceridemia in 55%, altered waist circumference in 17% and altered glycemia and/or diabetes in 23% of individuals. Abnormal waist and hypertriglyceridemia were more common in LDHIV-affected individuals. MS was diagnosed in 36%. In multivariate analysis, the factors associated with MS were: BMI >25 kg/m(2) (p<0.001), family history of obesity (p=0.01), indinavir (p=0.001) and age >40 years on HIV first detection (p=0.002). There was a trend to higher frequency of LDHIV among patients with MS (65% versus 50%, p=0.051). LDHIV prevalence among our patients (55%) was similar to previous reports from other countries. MS prevalence in these HIV-infected individuals seems to be similar to the prevalence reported on Brazilian non-HIV-infected adults.

The fatty acid binding protein-4 (FABP4) is a strong biomarker of metabolic syndrome and lipodystrophy in HIV-infected patients

Background The incidence of metabolic abnormalities in HIV-infected patients is increasing. Fatty acid binding protein-4 (FABP4) is an emerging biomarker for metabolic-related disturbances. We aimed to study FABP4 as a marker of metabolic syndrome (MS) or lipodystrophy (LD) in HIV patients. Methods FABP4 plasma concentrations were measured by enzyme-linked immunoassays in 183 HIV-infected patients, enrolled as part of a study aimed at identifying predictors of atherosclerosis. The presence of MS or LD was diagnosed according to standard clinical methods. Univariate and multivariate statistical analyses were performed. Results FABP4 concentration was significantly higher in those patients with either MS or LD criteria than those without any metabolic disturbance. Similarly, FABP4 concentration significantly increased with an increasing of MS features and was strongly correlated with body-mass index, triglycerides, HDL-cholesterol concentrations, insulin and blood pressure. Patients in the highest quartile of FABP4 presented a six-fold increased odds ratio for MS and a three-fold increased odds for LD, adjusted by age, sex, body-mass index and the antiretroviral therapy. Conclusions FABP4 is a strong plasma marker of metabolic disturbances in HIV-infected patients, and therefore, could serve to guide therapeutic intervention in this group of patients.