Identification of novel genetic variations in ABCB6 and GRN genes associated with HIV-associated lipodystrophy.

Protease inhibitors (PIs) are associated with an incidence of lipodystrophy among people living with HIV(PLHIV). Lipodystrophiesare characterised by the loss of adipose tissue. Evidence suggests that a patient's lipodystrophy phenotype is influenced by genetic mutation, age, gender, and environmental and genetic factors, such as single-nucleotide variants (SNVs). Pathogenic variants are considered to cause a more significant loss of adipose tissue compared to non-pathogenic. Lipid metabolising enzymes and transporter genes have a role in regulating lipoprotein metabolism and have been associated with lipodystrophy in HIV-infected patients (LDHIV). The long-term effect of the lipodystrophy syndrome is related to cardiovascular diseases (CVDs). Hence, we determined the SNVs of lipid metabolising enzymes and transporter genes in a total of 48 patient samples, of which 24 were with and 24 were without HIV-associated lipodystrophy (HIVLD) using next-generation sequencing. A panel of lipid metabolism, transport and elimination genes were sequenced. Three novel heterozygous non-synonymous variants at exon 8 (c.C1400A:p.S467Y, c.G1385A:p.G462E, and c.T1339C:p.S447P) in the ABCB6 gene were identified in patients with lipodystrophy. One homozygous non-synonymous SNV (exon5:c.T358C:p.S120P) in the GRN gene was identified in patients with lipodystrophy. One novelstop-gain SNV (exon5:c.C373T:p.Q125X) was found in the GRN gene among patients without lipodystrophy. Patients without lipodystrophy had one homozygous non-synonymous SNV (exon9:c.G1462T:p.G488C) in the ABCB6 gene. Our findings suggest that novel heterozygous non-synonymous variants in the ABCB6 gene may contribute to defective protein production, potentially intensifying the severity of lipodystrophy. Additionally, identifying a stop-gain SNV in the GRN gene among patients without lipodystrophy implies a potential role in the development of HIVLD.

Impact of inflammatory cytokine and adipokine gene variations in the development of HIV-associated lipodystrophy.

Cytokines affect lipid and glucose metabolism and also alter the body's habitus. They play a role in the development of lipodystrophy syndrome. Adipocytes secrete the pro-inflammatory cytokines IL-1, TNF-α and IL-6. The plasma cytokine concentration is associated with the percentage and distribution of fat tissue in the body. The metabolic disturbances are strongly associated with increased levels of pro-inflammatory cytokines (IL-1, IL-6 and TNF-α). Plasma levels of cytokines such as TNF-α, IL-6 and leptin were found to be increased while plasma resistin levels were found to be variable in patients suffering from obesity and type II diabetes mellitus. Until now, limited information has been available on the polymorphism of cytokine and adipokine genes in patients of HIV-associated lipodystrophy (HIVLD), which can contribute to individual variations in susceptibility to metabolic diseases, especially to HIVLD. Hence, we studied the association of cytokine and adipokine gene polymorphisms in various diseases and their impact on HIVLD. We carry out an extensive search using several databases, including PubMed, EMBASE and Google Scholar. The distribution of cytokine and adipokine gene polymorphisms and their expression levels varied among various populations. We examined the variants of cytokine and adipokine genes, which can contribute to individual variations in susceptibility to metabolic diseases, especially to HIVLD. In the current review, we present a brief account of the risk factors of HIVLD, the pathogenesis of HIVLD and the polymorphism of cytokine and adipokine genes in various diseases with special reference to their impact on HIVLD.

Effect of genetic variations in drug transporters, metabolizing enzyme and regulatory genes on the development of HIV-associated lipodystrophy.

Adipocytes play a crucial role in the metabolism of lipids and sugars. Their response varies depending on the circumstances or other factors influenced by physiological and metabolic stresses. People living with HIV (PLWH) experience different effects of HIV and highly active antiretroviral therapy (HAART) on their body fat. Some patients respond well to antiretroviral therapy (ART), while others taking similar regimens do not. The genetic makeup of patients has been strongly linked to the variable responses to HAART among PLWH. The cause of HIV-associated lipodystrophy syndrome (HALS) is not well understood, but it may be influenced by genetic variations in the host. The metabolism of lipid effectively modulates plasma triglyceride and high-density lipoprotein cholesterol levels in PLWH. Genes related to drug metabolism and transport play an important role in the transportation and metabolism of ART drugs. Genetic variation in metabolizing enzyme genes of antiretroviral drugs, lipid transport and transcription factor-related genes could interfere with fat storage and metabolism, contributing to the development of HALS. Hence we examined the impact of genes associated with transport, metabolism and various transcription factors in metabolic complications, and their impact on HALS. A study using databases such as PubMed, EMBASE and Google Scholar was conducted to understand the impact of these genes on metabolic complications and HALS. The present article discuss the changes in the expression and regulation of genes and their involvement in the lipid metabolism, lipolysis and lipogenesis pathways. Moreover, alteration of the drug transporter, metabolizing enzyme and various transcription factors can lead to HALS. Single-nucleotide polymorphisms in genes that play an essential role in drug metabolism and drug and lipid transportation may also contribute to individual differences in the emergence of metabolic and morphological alterations during HAART treatment.

REVERSIBILITY OF LIPOATROPHY IN HIV-INFECTED PATIENTS TAKING ANTIRETROVIRAL THERAPY: A COHORT STUDY WITH ULTRASOUND ASSESSMENT.

The aim of this study was to characterize and compare changes in subcutaneous fat in the malar, brachial and crural region in a cohort of HIV-infected patients taking antiretroviral therapy. This prospective longitudinal study included 77 patients who were selected from the initial cohort evaluated in 2007 and 2008. We examined reversibility of lipoatrophy measured by ultrasound over at least five-year period and factors related to its reversibility. All 46 patients who used stavudine switched from stavudine to another combination. Of 58 patients on zidovudine, 16 (28%) were on a zidovudine based regimen at the second follow up. There was evidence for subcutaneous fat increase in the malar area (p<0.001) and no increase in the brachial and crural areas. Patients who were smokers and had poor adherence to the Mediterranean diet had a thinner malar area at the follow up measurement (p=0.030) and smaller increase in subcutaneous malar fat compared to others (p=0.040). Our study suggested that modest increase of subcutaneous fat in malar area coincided with stopping stavudine and fewer usage of zidovudine. Lifestyle with non-adherence to the Mediterranean diet and smoking were associated with a smaller increase in subcutaneous malar fat.

Sex-specific fat mass ratio cutoff value identifies a high prevalence of cardio-metabolic disorders in people living with HIV.

BACKGROUND AND AIMS: HIV-associated lipodystrophy syndrome (HALS) contributes to the increased cardiovascular risk connoting people living with HIV (PLHIV). HALS recognition, based on clinical ground, may be inaccurate urging an objective instrumental diagnosis. The aim of this study is to search for the DXA-derived fat mass ratio (FMR) threshold, among those suggested for the diagnosis of HALS, able to identify PLHIV at high cardiovascular risk. METHODS AND RESULTS: In a cross-sectional analysis of 101 PLHIV (age 53 ± 11 years, men 55%) and 101 age- and sex-matched uninfected controls, DXA-derived FMR and anthropometric as well as cardio-metabolic parameters were assessed. PLHIV showed a higher FMR (1.15 ± 0.42 vs 0.95 ± 0.18, p < 0.01) together with a greater cardio-metabolic derangement than controls, in spite of lower BMI (24.3 ± 4.3 vs 26.9 ± 4.0 kg/m2, p < 0.01) and fat mass index (FMI, 6.6 ± 3.0 vs 9.2 ± 3.1 kg/m2, p < 0.01). Particularly, PLHIV with HALS (n = 28), defined as those with a FMR above 1.260 and 1.329 for men and women, respectively, had a greater prevalence of type 2 diabetes mellitus (18% vs 1%), insulin resistance (68% vs 27%), hypertriglyceridemia (50% vs 29%), hypertension (61% vs 30%) and metabolic syndrome (32% vs 10%) than those without HALS (p < 0.05 for all comparisons) and controls. At multivariate analyses, FMR in PLHIV was significantly associated (p < 0.05) with fasting glucose (ß [95%CI] = 0.5, [0.1-0.9]), insulin (44.6, [14.9-74.2]), HOMA-IR (1.6, [0.5-2.7]), triglycerides (1.0, [ 0.2-1.8]) and HDL-cholesterol (-2.1, [-3.9/-0.4]) levels. CONCLUSION: Sex-specific FMR thresholds, proposed for diagnosis of HALS, could represent new indices of cardio-metabolic derangement in PLHIV.

Genetic and cytometric analyses of subcutaneous adipose tissue in patients with hemophilia and HIV-associated lipodystrophy.

BACKGROUND: The authors recently performed plastic surgeries for a small number of patients with hemophilia, HIV infection, and morphologic evidence of lipodystrophy. Because the pathophysiological mechanism of HIV-associated lipodystrophy remains to be elucidated, we analyzed subcutaneous adipose tissues from the patients. METHODS: All six patients had previously been treated with older nucleoside analogue reverse-transcriptase inhibitors (NRTIs; stavudine, didanosine or zidovudine). Abdominal and inguinal subcutaneous fat samples were obtained from the HIV+ patients with hemophilia and HIV- healthy volunteers (n = 6 per group), and analyzed via DNA microarray, real-time PCR, flow cytometry and immunohistochemistry. RESULTS: The time from initial NRTI treatment to collecting samples were 21.7 years in average. Cytometric analysis revealed infiltration of inflammatory M1 macrophages into HIV-infected adipose tissue and depletion of adipose-derived stem cells, possibly due to exhaustion following sustained adipocyte death. Genetic analysis revealed that adipose tissue from HIV+ group had increased immune activation, mitochondrial toxicity, chronic inflammation, progressive fibrosis and adipocyte dysfunction (e.g. insulin resistance, inhibited adipocyte differentiation and accelerated apoptosis). Of note, both triglyceride synthesis and lipolysis were inhibited in adipose tissue from patients with HIV. CONCLUSIONS: Our findings provide important insights into the pathogenesis of HIV-associated lipodystrophy, suggesting that fat redistribution may critically depend on adipocytes' sensitivity to drug-induced mitochondrial toxicity, which may lead either to atrophy or metabolic complications.

Impact of strength training on bone mineral density in HIV-positive patients / Impacto do treinamento de força na densidade mineral óssea em pacientes HIV positivo

Abstract Introduction: Highly active antiretroviral therapy (HAART) transformed HIV from a fatal disease to a chronic one, but it has adverse effects, such as the lipodystrophy syndrome, characterized by morphological and metabolic changes, such as reduced bone mineral density (BMD), potentiating morbidities and mortality. Strength training (ST) aims to increase BMD, due to the osteogenic effect. Objective: To verify the impact of strength training on BMD in people with HIV. Methods: This is a quasi-experimental study, which included 40 people with a mean age of 50 ± 6 years, separated into trained group (TG, n = 20) and control group (CG, n = 20), with reduction in BMD, HIV-positive, using HAART and without exercising. BMD was assessed by DEXA in the lumbar spine, femoral neck and distal 1/3 of the radius, before and after 12 weeks, with the GT submitted to 36 ST and the CG without physical training in the DEXA evaluation in the same time interval. Results: TG had a significant increase with great effect on BMD in all segments: lumbar spine (p = 0.001; ES: 1.87), femoral neck (p = 0.003; ES: 2.20) and 1/3 distal of the radius (p = 0.001; ES: 1.81). Meanwhile, CG group showed a significant reduction with great effect on the femoral neck (p = 0.020; ES: 2.56) and 1/3 distal of the radius (p = 0.015; ES: 2.93), while the lumbar spine showed a great effect to reduce BMD (p = 0.293; ES: 1.78). Conclusion: ST can be used as a therapeutic resource to increase BMD in people with HIV, contributing to the advancement in the search for non-drug therapeutic practices.

Resumo Introdução: A terapia antirretroviral altamente ativa (HAART) transformou o HIV em uma doença crônica, apresentando efeitos adversos como a síndrome da lipodistrofia, caracterizada por alterações morfológicas e metabólicas, como redução da densidade mineral óssea (DMO), potencializando morbidades e mortalidades. O treinamento de força (TF) tem como proposta aumentar a DMO, devido ao efeito osteogênico. Objetivo: Verificar o impacto do TF na DMO em pessoas com HIV. Métodos: Trata-se de um estudo quase-experimental que incluiu 40 pessoas com idade média de 50 ± 6 anos, separadas em grupo treinado (GT, n = 20) e grupo controle (GC, n = 20), com redução na DMO, HIV positivo, usando HAART e sem praticar exercícios físicos. A DMO foi avaliada pelo DEXA na coluna lombar, colo do fêmur e 1/3 distal do rádio, antes e após 12 semanas, com o GT submetido a 36 sessões de TF e o GC sem exercício durante o mesmo período. Resultados: O GT teve aumento significante com grande efeito em todos os segmentos: coluna lombar (p = 0,001; ES: 1,87), colo do fêmur (p = 0,003; ES: 2,20) e 1/3 distal do rádio (p = 0,001; ES: 1,81), enquanto o GC apresentou redução significante com grande efeito no colo do fêmur (p = 0,020; ES: 2,56), 1/3 distal do rádio (p = 0,015; ES: 2,93) e apenas grande efeito na coluna lombar (p = 0,293; ES: 1,78). Conclusão: O TF pode ser utilizado como recurso terapêutico para aumentar a DMO em pessoas com HIV, contribuindo para o avanço nas buscas de práticas terapêuticas não medicamentosas.

Altered pattern of circulating miRNAs in HIV lipodystrophy perturbs key adipose differentiation and inflammation pathways.

We identified a microRNA (miRNA) profile characterizing HIV lipodystrophy and explored the downstream mechanistic implications with respect to adipocyte biology and the associated clinical phenotype. miRNA profiles were extracted from small extracellular vesicles (sEVs) of HIV-infected individuals with and without lipodystrophic changes and individuals without HIV, among whom we previously showed significant reductions in adipose Dicer expression related to HIV. miR-20a-3p was increased and miR-324-5p and miR-186 were reduced in sEVs from HIV lipodystrophic individuals. Changes in these miRNAs correlated with adipose Dicer expression and clinical markers of lipodystrophy, including fat redistribution, insulin resistance, and hypertriglyceridemia. Human preadipocytes transfected with mimic miR-20a-3p, anti-miR-324-5p, or anti-miR-186 induced consistent changes in latent transforming growth factor beta binding protein 2 (Ltbp2), Wisp2, and Nebl expression. Knockdown of Ltbp2 downregulated markers of adipocyte differentiation (Fabp4, Pparγ, C/ebpa, Fasn, adiponectin, Glut4, CD36), and Lamin C, and increased expression of genes involved in inflammation (IL1ß, IL6, and Ccl20). Our studies suggest a likely unique sEV miRNA signature related to dysregulation of Dicer in adipose tissue in HIV. Enhanced miR-20a-3p or depletion of miR-186 and miR-324-5p may downregulate Ltbp2 in HIV, leading to dysregulation in adipose differentiation and inflammation, which could contribute to acquired HIV lipodystrophy and associated metabolic and inflammatory perturbations.

Self-reported HIV/HAART-associated Lipodystrophy and Modifiable Risk Factors for Cardiovascular Disease

Abstract Background Patient self-report is the most common diagnostic tool in the literature to detect HIV/HAART-associated lipodystrophy. However, data on the association of cardiovascular risk factors with HIV/HAART-associated lipodystrophy assessed by self-report are still missing. Objectives To determine the prevalence of self-reported HIV/HAART-associated lipodystrophy and to identify independent associations between traditional modifiable cardiovascular risk factors and self-reported lipodystrophy. Methods We conducted a retrospective observational study at an outpatient infectious disease clinic in the Central-West of Brazil to identify the association between traditional modifiable cardiovascular risk factors and self-reported lipodystrophy. Sedentary lifestyle, smoking status, family history of cardiovascular disease, hypertension, diabetes, dyslipidemia, increased waist circumference and overweight were the cardiovascular risk factors assessed. Self-reported HIV/HART-associated lipodystrophy was categorized as: mild (noticeable by patients' close inspection), moderate (easily noticeable by patient and physician) or severe (readily noticeable by a casual observer). Prevalence ratio (PR) and 95% confidence interval (CI95%) were calculated. Multivariate Poisson's regression was used to analyze factors associated to HIV/HAART-associated lipodystrophy assessed by self-report considering a significance level of 5%. Results A total of 183 patients were included, with a mean age of 39.3±10.9 years. Most of the sample were male (77.6%), non-white (50.8%) and single (53.0%). The overall prevalence of HIV/HAART-associated lipodystrophy was 52.5% (95% CI 44.96 - 59.88). Severe lipodystrophy was observed in more than half patients (55.2%). No traditional modifiable cardiovascular risk factor was independently associated with lipodystrophy. Female sex (PR 1.49; 95% CI 1.15 - 1.95; p =0.003), time of HIV infection diagnosis of 1-3 years (PR 1.83; 95% CI 1.09 - 3.08; p =0.002) and a positive family history of CVD (PR 1.62; 95% CI 1.11 - 2.36; p <0.001) were independently associated with lipodystrophy. Conclusion HIV/HAART-associated lipodystrophy assessed by patient self-report was not associated with traditional modifiable cardiovascular risk factors. Int J Cardiovasc Sci. 2020; [online].ahead print, PP.0-0

Adipocytokine dysregulation, abnormal glucose metabolism, and lipodystrophy in HIV-infected adolescents receiving protease inhibitors.

BACKGROUND: Lipodystrophy is common in HIV-infected patients receiving protease inhibitors (PIs), stavudine, and zidovudine. Adipocytokines may be altered in lipodystrophy. We evaluated risk factors, adipocytokine levels, insulin resistance, and lipid profiles in HIV-infected adolescents with different lipodystrophy types. METHODS: A cross-sectional study was conducted in 80 perinatally HIV-infected adolescents receiving PI-based highly active antiretroviral therapy for ≥ 6 months. Patients underwent oral glucose tolerance tests and measurements of high-molecular-weight (HMW) adiponectin, leptin, resistin, insulin, and lipids. They were classified into 3 groups based on the clinical findings: no lipodystrophy, isolated lipoatrophy, and any lipohypertrophy (isolated lipohypertrophy or combined type). RESULTS: Of the 80 patients (median age, 16.7 years), 18 (22.5%) had isolated lipoatrophy, while 8 (10%) had any lipohypertrophy (four with isolated lipohypertrophy, and four with the combined type). In a multivariate analysis, longer exposure to stavudine (OR: 1.03; 95% CI, 1.01-1.06; p = 0.005) and indinavir (OR: 1.03; 95% CI, 1.01-1.06; p = 0.012) were associated with lipoatrophy, while longer exposure to didanosine (OR: 1.04; 95% CI, 1.01-1.08; p = 0.017) and indinavir (OR: 1.10; 95% CI, 1.00-1.21; p = 0.045) were associated with any lipohypertrophy. Leptin levels were highest in the any-lipohypertrophy group and lowest in the isolated-lipoatrophy group (p = 0.013). HMW adiponectin levels were significantly lowest in the any-lipohypertrophy group and highest in the no-lipodystrophy group (p = 0.001). There were no significant differences in the levels of resistin among the three groups (p = 0.234). The prevalence of insulin resistance (p = 0.002) and prediabetes/diabetes (p < 0.001) were significantly highest in the any-lipohypertrophy group. Patients with lipoatrophy and those without lipodystrophy had comparable degrees of insulin resistance (p = 0.292). In multiple linear regression analysis, adjusted for age, sex, and waist-height ratio, HMW adiponectin levels were associated with Matsuda index (ß = 0.5; p = 0.003) and quantitative insulin sensitivity check index (QUICKI) (ß = 40.1; p = 0.010) and almost significantly associated with homeostatic model assessment of insulin resistance (HOMA-IR) (p = 0.054). Leptin and resistin levels were not associated with HOMA-IR, Matsuda index, or QUICKI (all p > 0.05). CONCLUSIONS: Abnormal glucose metabolism and dysregulation of adipocytokines were common in the HIV-infected adolescents with lipohypertrophy and the combined type. Preventive screening for cardiovascular diseases caused by metabolic alterations should be routinely performed.

Association of the polymorphisms of the genes APOC3 (rs2854116), ESR2 (rs3020450), HFE (rs1799945), MMP1 (rs1799750) and PPARG (rs1801282) with lipodystrophy in people living with HIV on antiretroviral therapy: a systematic review.

The aim of this study was to perform a systematic review to identify data reported in the literature concerning the association of APOC3 (rs2854116), ESR2 (rs3020450), HFE (rs1799945), MMP1 (rs1799750) and PPARG (rs1801282) polymorphisms with lipodystrophy in people living with HIV (PLWHIV) on antirretroviral therapy. The research was conducted in six databases and the studies were selected in two steps. First, a search was undertaken in the following electronic databases: PubMed, Science Direct, Medline, World Wide Science, Directory of Open Access Journals, Scielo, Lilacs and Medcarib. The titles and abstracts of 24,859 articles were read to select those that match the elegibilty criteria. Five papers that addressed the association of HAART, lipodystrophy and polymorphisms were selected for the review. There was no association between the polymorphisms of the genes APOC3 and PPARG and lipodystrophy. Another study described an association between the variant allele (G) of HFE and protection concerning the development of lipoatrophy (0.02) when compared with the reference allele (C). On the other hand, the variant allele (T) of the ESR2 gene was associated with the development of lipoatrophy (p = 0.007) when compared with the reference allele (C). In addition, the genotype and the variant allele of the gene MMP1 (2G) were associated with lipodystrophy in PLWHIV on HAART (p = 0.0002 and p = 0.0008, respectively). Therefore, further studies with other populations, involving PLWHIV on HAART are necessary to better understand the role of genetic markers, which may be involved in a predisposition to lipodystrophy.

Association between changes in body fat distribution, biochemical profile, time of HIV diagnosis, and antiretroviral treatment in adults living with and without virus infection.

OBJECTIVES: Individuals living with HIV seem to be more prone to changes in the redistribution of body fat, characterized as lipodystrophy, which may occur in conjunction with metabolic diseases. In the present study, such impacts were assessed in adults with and without HIV and associated with the time of virus diagnosis and treatment with antiretroviral. METHODS: A cross-sectional study with 123 adults, in which 87 had HIV and 36 without HIV, of both sexes, in outpatient follow-up at the Specialized Care Service (SAE) in Macaé-RJ. The following were made: 1) Alteration in body fat distribution, measured by anthropometric parameters and self-reported lipodystrophy; 2) Biochemical profile; 3) Association between HIV diagnosis time and antiretroviral treatment. RESULTS: 54.47% (n = 67) males, 45.52% (n = 56) females, mean age 37 years. Of these 87 were people living with HIV, 29% (n = 25) had self-reported lipodystrophy, mean time of virus infection, and antiretroviral treatment (5.80 ± 4.56 and 5.14 ± 3.82 years), respectively. Patients with self-reported lipodystrophy had a greater change in body fat distribution between 3-6 years of HIV diagnosis and a negative cholesterol profile. The antiretroviral treatment time influenced total cholesterol and triglycerides, even for patients without self-reported lipodystrophy, with a further nine years under treatment. CONCLUSION: In this study, the negative cholesterol profile was mainly related to antiretroviral treatment time, even for patients without self-reported lipodystrophy, and changes in body fat distribution, measured by anthropometry, was especially associated with time for HIV infection in those with lipodystrophy self-reported.

Lipodystrophic syndrome of HIV and associated factors: a study in a university hospital. / Síndrome lipodistrófica do HIV e seus fatores associados: um estudo em um hospital universitário.

The use of antiretroviral drugs has increased the survival of HIV patients, but may have side effects, such as lipodystrophic syndrome. This article aims to identify the frequency of the lipodystrophic syndrome and its associated factors in patients with HIV using antiretroviral therapy. It involved a cross-sectional study with HIV patients, monitored on an outpatient basis. The syndrome was evaluated by the association of two parameters: peripheral weight loss through the lipodystrophy severity scale and central fat accumulation, measured by the hip waist ratio. Poisson regression analysis was performed to identify the associated variables. Of the 104 patients evaluated, 27.9% presented the syndrome. After adjustment, the female sex (PRadjusted = 2.16 CI95% 1.43-3.39), being overweight (PRadjusted = 2.23 CI95% 1.35-2.65) and a longer period of use of antiretrovirals (PRadjusted = 1.64 CI95% 1.16-2.78), remained positively associated with the syndrome. On the other hand, a negative association with CD4 count £ 350 (PRadjusted = 0.39 CI95% 0.10-0.97) was observed The high prevalence of the syndrome and its association with specific groups reinforce the need for adequate follow-up and early identification to intervene in modifiable factors.

O uso de antirretroviral aumentou a sobrevida dos portadores do HIV, porém pode acarretar efeitos colaterais, como a síndrome lipodistrófica. O objetivo deste artigo é identificar a frequência da síndrome lipodistrófica e seus fatores associados em pacientes portadores do HIV em uso de terapia antiretroviral. Estudo transversal com pacientes acompanhados ambulatorialmente. A síndrome foi avaliada pela associação de dois parâmetros: emagrecimento periférico através da escala de gravidade de lipodistrofia e acúmulo de gordura central, mensurado pela relação cintura quadril. Para identificar as variáveis associadas foi realizada a análise de Regressão de Poisson. Dos 104 pacientes avaliados, 27,9% apresentaram a síndrome. Após ajuste, ser do sexo feminino (RPajustada = 2,16 IC95%1,43-3,39), ter excesso de peso (RPajustada = 2,23 IC95%1,35-2,65) e um maior tempo de uso dos antirretrovirais (RPajustada = 1,64 IC95%1,16-2,78) permaneceram positivamente associados à síndrome. Por outro lado, foi observada uma associação negativa com a contagem de CD4 £ 350 (RPajustada = 0,39 IC95%0,10-0,97). A alta prevalência da síndrome e sua associação com grupos específicos reforçam a necessidade do adequado acompanhamento e identificação precoce como forma de intervir nos fatores modificáveis.

Síndrome lipodistrófica do HIV e seus fatores associados: um estudo em um hospital universitário / Lipodystrophic syndrome of HIV and associated factors: a study in a university hospital

Resumo O uso de antirretroviral aumentou a sobrevida dos portadores do HIV, porém pode acarretar efeitos colaterais, como a síndrome lipodistrófica. O objetivo deste artigo é identificar a frequência da síndrome lipodistrófica e seus fatores associados em pacientes portadores do HIV em uso de terapia antiretroviral. Estudo transversal com pacientes acompanhados ambulatorialmente. A síndrome foi avaliada pela associação de dois parâmetros: emagrecimento periférico através da escala de gravidade de lipodistrofia e acúmulo de gordura central, mensurado pela relação cintura quadril. Para identificar as variáveis associadas foi realizada a análise de Regressão de Poisson. Dos 104 pacientes avaliados, 27,9% apresentaram a síndrome. Após ajuste, ser do sexo feminino (RPajustada = 2,16 IC95%1,43-3,39), ter excesso de peso (RPajustada = 2,23 IC95%1,35-2,65) e um maior tempo de uso dos antirretrovirais (RPajustada = 1,64 IC95%1,16-2,78) permaneceram positivamente associados à síndrome. Por outro lado, foi observada uma associação negativa com a contagem de CD4 £ 350 (RPajustada = 0,39 IC95%0,10-0,97). A alta prevalência da síndrome e sua associação com grupos específicos reforçam a necessidade do adequado acompanhamento e identificação precoce como forma de intervir nos fatores modificáveis.

Abstract The use of antiretroviral drugs has increased the survival of HIV patients, but may have side effects, such as lipodystrophic syndrome. This article aims to identify the frequency of the lipodystrophic syndrome and its associated factors in patients with HIV using antiretroviral therapy. It involved a cross-sectional study with HIV patients, monitored on an outpatient basis. The syndrome was evaluated by the association of two parameters: peripheral weight loss through the lipodystrophy severity scale and central fat accumulation, measured by the hip waist ratio. Poisson regression analysis was performed to identify the associated variables. Of the 104 patients evaluated, 27.9% presented the syndrome. After adjustment, the female sex (PRadjusted = 2.16 CI95% 1.43-3.39), being overweight (PRadjusted = 2.23 CI95% 1.35-2.65) and a longer period of use of antiretrovirals (PRadjusted = 1.64 CI95% 1.16-2.78), remained positively associated with the syndrome. On the other hand, a negative association with CD4 count £ 350 (PRadjusted = 0.39 CI95% 0.10-0.97) was observed The high prevalence of the syndrome and its association with specific groups reinforce the need for adequate follow-up and early identification to intervene in modifiable factors.

Association between changes in body fat distribution, biochemical profile, time of HIV diagnosis, and antiretroviral treatment in adults living with and without virus infection

SUMMARY OBJECTIVES Individuals living with HIV seem to be more prone to changes in the redistribution of body fat, characterized as lipodystrophy, which may occur in conjunction with metabolic diseases. In the present study, such impacts were assessed in adults with and without HIV and associated with the time of virus diagnosis and treatment with antiretroviral. METHODS A cross-sectional study with 123 adults, in which 87 had HIV and 36 without HIV, of both sexes, in outpatient follow-up at the Specialized Care Service (SAE) in Macaé-RJ. The following were made: 1) Alteration in body fat distribution, measured by anthropometric parameters and self-reported lipodystrophy; 2) Biochemical profile; 3) Association between HIV diagnosis time and antiretroviral treatment. RESULTS 54.47% (n = 67) males, 45.52% (n = 56) females, mean age 37 years. Of these 87 were people living with HIV, 29% (n = 25) had self-reported lipodystrophy, mean time of virus infection, and antiretroviral treatment (5.80 ± 4.56 and 5.14 ± 3.82 years), respectively. Patients with self-reported lipodystrophy had a greater change in body fat distribution between 3-6 years of HIV diagnosis and a negative cholesterol profile. The antiretroviral treatment time influenced total cholesterol and triglycerides, even for patients without self-reported lipodystrophy, with a further nine years under treatment. CONCLUSION In this study, the negative cholesterol profile was mainly related to antiretroviral treatment time, even for patients without self-reported lipodystrophy, and changes in body fat distribution, measured by anthropometry, was especially associated with time for HIV infection in those with lipodystrophy self-reported.

RESUMO OBJETIVOS Indivíduos vivendo com HIV parecem mais propensos às alterações na redistribuição da gordura corporal, caracterizada como lipodistrofia, podendo acontecer em conjunto com as metabólicas. No presente estudo avaliaram-se tais impactos em adultos com e sem HIV e se associou ao tempo de diagnóstico do vírus e tratamento com antirretroviral. MÉTODOS Estudo tipo transversal, com 123 adultos, no qual 87 tinham HIV e 36 sem HIV, de ambos os sexos, em seguimento ambulatorial no Serviço de Atendimento Especializado (SAE) em Macaé - RJ. Foram feitos: 1) Alteração na distribuição da gordura corporal, mensurados por parâmetros antropométricos e lipodistrofia autorreferida; 2) Perfil bioquímico; 3) Associação entre tempo diagnóstico do HIV e tratamento com antirretroviral. RESULTADOS Incluíram-se 54,47% (n=67) do sexo masculino, 45,52% (n=56) do feminino, com média de idade de 37 anos. Destes, 87 eram pessoas vivendo com HIV, 29% (n=25) possuíam lipodistrofia autorreferida; tempo médio de infecção pelo vírus e tratamento antirretroviral (5,80±4,56 e 5,14±3,82 anos), respectivamente. Os pacientes com lipodistrofia autorreferida tiveram maior alteração na distribuição da gordura corporal entre 3-6 anos de diagnóstico do HIV e um perfil colesterolêmico negativo. O tempo de tratamento com antirretroviral influenciou o colesterol total e os triglicerídeos, mesmo para os pacientes sem lipodistrofia autorreferida, com mais de nove anos sob tratamento. CONCLUSÃO Neste estudo, o perfil colesterolêmico negativo se relacionou principalmente ao tempo de tratamento com antirretroviral, mesmo para os pacientes sem lipodistrofia autorreferida e as alterações na distribuição da gordura corporal, mensuradas por antropometria, se associaram especialmente ao tempo de infecção pelo HIV naqueles com lipodistrofia autorreferida.

Subcutaneous Adipocyte Adenosine Triphosphate Levels in HIV Infected Patients.

Lipoatrophy, or fat wasting, remains a syndrome plaguing HIV+ patients receiving antiretroviral (ARV) therapy. Both HIV infection per se and certain ARV are associated with lowered adipose tissue mitochondrial deoxyribonucleic acid (mtDNA) and mitochondrial ribonucleic acid (mtRNA) levels, but effects on adenosine triphosphate (ATP) production are unclear. We hypothesized that such alterations would accompany lowering of ATP levels in fat of HIV+ patients and would be worse in those displaying lipoatrophy. Gluteal-fold, subcutaneous adipose tissue was obtained from HIV seronegative control patients, from HIV+ ARV-naive patients, and those on ARV with or without lipoatrophy. Cellular ATP was measured in isolated adipocytes and preadipocyte fraction cells by bioluminescence. mtDNA copies/cell and oxidative phosphorylation (OXPHOS) mtRNA transcripts were evaluated by quantitative polymerase chain reactions. ATP levels were consistently higher in preadipocyte fraction cells than adipocytes, but values strongly correlated with each other (r = 0.66, p < .001). ATP levels in adipocytes were higher in both ARV-naive and nonlipoatrophic HIV+ patients compared to seronegative controls, but significantly lower in adipocytes and preadipocytes of lipoatrophic versus other HIV+ patients. Fat mtDNA copies/cell and OXPHOS mtRNA transcripts were lower in lipoatrophic patient samples compared to HIV seronegative. The ratio of specific OXPHOS transcripts to each other was significantly higher in nonlipoatrophic patients versus all groups, and this ratio correlated significantly with ATP levels in adipocytes. Thus, HIV infection is associated with an increase in adipose tissue ATP stores. Decreases in adipose mtDNA and OXPHOS mtRNA are found in those with HIV on ARV; however, ATP level is effected only in patients displaying lipoatrophy.

HIV and pericardial fat are associated with abnormal cardiac structure and function among Ugandans.

OBJECTIVES: To examine the relationship between pericardial fat (PCF) and cardiac structure and function among HIV-infected patients in the sub-Saharan African country of Uganda. People living with HIV (PLHIV) have altered fat distribution and an elevated risk for heart failure. Whether altered quantity and radiodensity of fat surrounding the heart relates to cardiac dysfunction in this population is unknown. METHODS: One hundred HIV-positive Ugandans on antiretroviral therapy were compared with 100 age and sex-matched HIV-negative Ugandans; all were >45 years old with >1 cardiovascular disease risk factor. Subjects underwent ECG-gated non-contrast cardiac CT and transthoracic echocardiography with speckle tracking strain imaging. Multivariable linear and logistic regression models were used to explore the association of PCF with echocardiographic outcomes. RESULTS: Median age was 55% and 62% were female. Compared with uninfected controls, PLHIV had lower body mass index (27 vs 30, p=0.02) and less diabetes (26% vs 45%, p=0.005). Median left ventricular (LV) ejection fraction was 67%. In models adjusted for traditional risk factors, HIV was associated with 10.3 g/m2 higher LV mass index (LVMI) (95% CI 3.22 to 17.4; p=0.005), 0.87% worse LV global longitudinal strain (GLS) (95% CI -1.66 to -0.07; p=0.03) and higher odds of diastolic dysfunction (OR 1.96; 95% CI 0.95 to 4.06; p=0.07). In adjusted models, PCF volume was significantly associated with increased LVMI and worse LV GLS, while PCF radiodensity was associated with worse LV GLS (all p<0.05). CONCLUSIONS: In Uganda, HIV infection, PCF volume and density are associated with abnormal cardiac structure and function.