RESUMO
In HIV-infected patients, combined antiretroviral therapy (cART) is associated to adipose tissue redistribution known as lipodystrophy and associated cardiometabolic risk. This study aimed to evaluate the evolution of body composition in HIV-infected patients, with and without lipodystrophy, over 2 yr. We evaluated anthropometric parameters and body composition by whole-body dual-energy X-ray absorptiometry in 144 HIV-infected patients on cART. We defined lipodystrophy by fat mass ratio. Lipodystrophy was present in 45.77% of the patients. These patients presented higher HIV infection duration, cART duration, and CD4+ cell count, with no differences regarding gender, age, body mass index, and viral load. Patients with lipodystrophy showed an increase in total fat mass (9.9%) and upper-limbs fat mass (17.6%), with a decrease in total, trunk, and lower-limbs fat-free mass (2.2%; 2.2%, and 3.9%, respectively), over 2 yr. In patients without lipodystrophy, the trunk fat-free mass decreased 1.9% over time, and no changes were observed in the other studied parameters. In patients with lipodystrophy, there was predominantly a central fat mass gain, with no changes in lower limbs, suggesting that peripheral adipocytes lose their regenerative capacity.
Assuntos
Adiposidade , Fármacos Anti-HIV/uso terapêutico , Síndrome de Lipodistrofia Associada ao HIV/tratamento farmacológico , Síndrome de Lipodistrofia Associada ao HIV/fisiopatologia , Absorciometria de Fóton , Adulto , Índice de Massa Corporal , Contagem de Linfócito CD4 , Quimioterapia Combinada , Feminino , Síndrome de Lipodistrofia Associada ao HIV/imunologia , Humanos , Gordura Intra-Abdominal/diagnóstico por imagem , Estudos Longitudinais , Extremidade Inferior , Masculino , Pessoa de Meia-Idade , Gordura Subcutânea/diagnóstico por imagem , Tronco , Extremidade Superior , Circunferência da Cintura , Relação Cintura-QuadrilRESUMO
BACKGROUND: Chronic HIV infection is associated with low-level inflammation and increased risk of chronic diseases and mortality. The objective was to assess the effects of moderate intensity exercise on metabolic and inflammatory markers in HIV-infected treated persons. METHODS: This was a pilot study enrolling cART-treated, sedentary persons with metabolic complications in a 12-week protocol, consisting of three sessions per week of 60 min brisk walking with (strength-walk group) or without (walk group) 30 min circuit-training. Assessments at baseline and week 12 (W12) included body morphometrics and total body dual-energy X-ray absorptiometry; lipid and glucose blood profile; plasma level of high sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), D-dimer, interleukin-18 (IL-18), soluble CD14, and CD38 and HLA-DR expression on CD4+ and CD8+ T-cells. RESULTS: Forty-nine patients were included and 35 (71%) completed the program: 21 in the walk and 14 in the strength-walk group. At W12, significant improvements were observed of body mass index, waist and hip circumference, and total cholesterol both overall and in the walk group, and of LDL cholesterol in both training groups. In the whole group, significant reductions were observed in hsCRP, IL-6, D-dimer, IL-18, and of CD8+/CD38+/HLA-DR+ cell frequencies. HsCRP and CD8+/CD38+/HLA-DR+ frequency decreased significantly in both training groups when examined separately whereas IL-6 and D-dimer in the walk group only. CONCLUSIONS: Brisk walking, with or without strength exercise, could improve lipid profile and inflammatory markers in chronic HIV infection. TRIAL REGISTRATION: ACTRN12615001258549, registered 17 November 2015, "retrospectively registered" Web address of trial: http://www.ANZCTR.org.au/ACTRN12615001258549.aspx.
Assuntos
Fármacos Anti-HIV/uso terapêutico , Terapia por Exercício/métodos , Infecções por HIV/terapia , Síndrome de Lipodistrofia Associada ao HIV/terapia , Treinamento Resistido/métodos , Caminhada , ADP-Ribosil Ciclase 1/imunologia , Absorciometria de Fóton , Adulto , Biomarcadores , Glicemia/metabolismo , Composição Corporal , Proteína C-Reativa/imunologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , HDL-Colesterol/metabolismo , LDL-Colesterol/metabolismo , Exercício Físico , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Citometria de Fluxo , Hemoglobinas Glicadas/metabolismo , Infecções por HIV/imunologia , Infecções por HIV/metabolismo , Síndrome de Lipodistrofia Associada ao HIV/imunologia , Síndrome de Lipodistrofia Associada ao HIV/metabolismo , Antígenos HLA-DR/imunologia , Humanos , Inflamação , Insulina/metabolismo , Interleucina-18/imunologia , Interleucina-6/imunologia , Receptores de Lipopolissacarídeos/imunologia , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Triglicerídeos/metabolismo , Circunferência da Cintura , Teste de CaminhadaRESUMO
OBJECTIVE: To assess the role of HIV and monocytes/macrophages in adipose tissue dysregulation. METHODS: Cross-sectional study in 5 groups: HIV seronegative, HIV+ antiretroviral therapy (ART)-naive, HIV+ nonlipoatrophic on zidovudine- and/or stavudine-containing ART, HIV+ lipoatrophic on similar ART, and HIV+ on abacavir- or tenofovir-containing ART. HIV DNA in circulating monocyte subsets was quantitated by real-time polymerase chain reaction. Biopsied subcutaneous fat was examined for macrophage content by CD68 staining. Isolated adipocytes and macrophages were cultured and the supernatant assayed for secretory products by Luminex multiplex cytokine technology. RESULTS: Sixty-nine subjects were enrolled. Lipoatrophic subjects had higher median HIV DNA levels (270.5 copies/10 cells) in circulating peripheral CD14CD16 co-expressing monocyte subsets compared with subjects who were ART-naive (25.0 copies), nonlipoatrophic (15.0 copies), or on abacavir/tenofovir (57.5 copies), P < 0.01. Group differences in adipocytes and adipose macrophage content were marginal. Although adipocyte secretory products were similar, HIV-infected subjects had higher adipose macrophage-derived interleukin (IL)-12p40, IL-6, IL-8, and monocyte inflammatory protein 1 alpha and lower eotaxin and interferon gamma levels than HIV seronegative subjects (P < 0.05). Within HIV-infected subjects, adipose macrophage secretory products were comparable between subjects naive with ART versus those on ART. CONCLUSIONS: Circulating HIV-infected and proinflammatory CD14CD16 monocyte subsets contribute to the pathogenesis of HIV-associated lipoatrophy. Among HIV-infected individuals, macrophages, rather than adipocytes, are the primary source of low-grade inflammation in subcutaneous adipose tissue. HIV infection modifies these macrophages to a more proinflammatory phenotype, and these changes are not substantially mitigated by the use of ART.
Assuntos
Tecido Adiposo/imunologia , Tecido Adiposo/fisiopatologia , Infecções por HIV/complicações , Síndrome de Lipodistrofia Associada ao HIV/imunologia , Síndrome de Lipodistrofia Associada ao HIV/fisiopatologia , Macrófagos/imunologia , Monócitos/imunologia , Adulto , Estudos Transversais , Feminino , Infecções por HIV/imunologia , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: HIV/AIDS-Associated Lipodystrophy Syndrome includes changes in body fat distribution, with or without metabolic changes. The loss of fat from the face, called facial lipoatrophy, is one of the most stigmatizing signs of the syndrome. OBJECTIVES: To evaluate the effect of FL treatment using polymethylmethacrylate (PMMA) implants on disease progression, assessed by viral load and CD4 cell count. METHODS: This was a prospective study of 44 patients treated from July 2009 to December 2010. Male and female patients, aged over 18 years, with clinically detectable FL and who had never been treated were included in the study. PMMA implantation was done to fill atrophic areas. Laboratory tests were conducted to measure viral load and CD4 count before and after treatment. RESULTS: Of the 44 patients, 72.72% were male and 27.27% female, mean age of 44.38 years. Before treatment, 82% of patients had undetectable viral load, which increased to 88.6% after treatment, but without statistical significance (p = 0.67). CD4 count before treatment ranged from 209 to 1293, averaging 493.97. After treatment, the average increased to 548.61. The increase in CD4 count after treatment was statistically significant with p = 0.02. CONCLUSION: The treatment of FL with PMMA implants showed a statistically significant increase in CD4 count after treatment, revealing the impact of FL treatment on disease progression. Viral load before and after treatment did not vary significantly.
Assuntos
Contagem de Linfócito CD4 , Síndrome de Lipodistrofia Associada ao HIV/terapia , Polimetil Metacrilato/uso terapêutico , Carga Viral , Adulto , Materiais Biocompatíveis/uso terapêutico , Progressão da Doença , Face , Feminino , Síndrome de Lipodistrofia Associada ao HIV/imunologia , Síndrome de Lipodistrofia Associada ao HIV/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Próteses e Implantes , Valores de Referência , Estatísticas não Paramétricas , Resultado do TratamentoRESUMO
BACKGROUND: HIV/AIDS-Associated Lipodystrophy Syndrome includes changes in body fat distribution, with or without metabolic changes. The loss of fat from the face, called facial lipoatrophy, is one of the most stigmatizing signs of the syndrome. OBJECTIVES: To evaluate the effect of FL treatment using polymethylmethacrylate (PMMA) implants on disease progression, assessed by viral load and CD4 cell count. METHODS: This was a prospective study of 44 patients treated from July 2009 to December 2010. Male and female patients, aged over 18 years, with clinically detectable FL and who had never been treated were included in the study. PMMA implantation was done to fill atrophic areas. Laboratory tests were conducted to measure viral load and CD4 count before and after treatment. RESULTS: Of the 44 patients, 72.72% were male and 27.27% female, mean age of 44.38 years. Before treatment, 82% of patients had undetectable viral load, which increased to 88.6% after treatment, but without statistical significance (p = 0.67). CD4 count before treatment ranged from 209 to 1293, averaging 493.97. After treatment, the average increased to 548.61. The increase in CD4 count after treatment was statistically significant with p = 0.02. CONCLUSION: The treatment of FL with PMMA implants showed a statistically significant increase in CD4 count after treatment, revealing the impact of FL treatment on disease progression. Viral load before ...
FUNDAMENTOS: A Síndrome Lipodistrófica Associada ao HIV/AIDS compreende alterações na distribuição da gordura corporal, acompanhada ou não de alterações metabólicas. A perda da gordura facial, chamada lipoatrofia facial, é dos sinais mais estigmatizantes da síndrome. OBJETIVOS: Avaliar o impacto do tratamento dalipoatrofia facial com implante de polimetilmetacrilato sobre a progressão da doença, avaliada pela contagem da carga viral e a contagem de células CD4. MÉTODOS: Estudo prospectivlipoatrofia facial clinicamente detectável e sem tratamento prévio. Foi realizado implante de polimetilmetacrilato para preenchimento das áreas atróficas. Foram realizadas contagem da carga viral e células CD4 antes e após o tratamento. RESULTADOS: Dos 44 pacientes, 72,72% eram do sexo masculino e 27,27% do feminino, e idade média de 44,38 anos. Antes do tratamento, 82% dos pacientes apresentavam carga viral indetectável, que aumentou para 88,6% após o tratamento, mas sem significância estatística (p=0,67). A contagem de CD4 antes do implante variou de 209 a 1293, com média de 493,97. Após o tratamento, essa média aumentou para 548,61. O aumento do CD4 após o tratamento foi estatisticamente significativo, com p=0,02. CONCLUSÃO: O tratamento dalipoatrofia facial com implante de polimetilmetacrilato ...
Assuntos
Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Síndrome de Lipodistrofia Associada ao HIV/terapia , Polimetil Metacrilato/uso terapêutico , Carga Viral , Materiais Biocompatíveis/uso terapêutico , Progressão da Doença , Face , Síndrome de Lipodistrofia Associada ao HIV/imunologia , Síndrome de Lipodistrofia Associada ao HIV/virologia , Estudos Prospectivos , Próteses e Implantes , Valores de Referência , Estatísticas não Paramétricas , Resultado do TratamentoRESUMO
BACKGROUND: HIV lipodystrophy - characterized by peripheral lipoatrophy, with or without central fat accumulation - confers increased metabolic risk. However, the functional activity of HIV lipodystrophic tissue in relation to metabolic risk has yet to be fully explored in vivo through the use of non-invasive imaging techniques. This study assesses the relationship between FDG uptake in various fat depots and metabolic/immune parameters among subjects with HIV lipodystrophy. METHODS: Lipodystrophic men on antiretroviral therapy underwent whole-body (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET)/computed tomography scans and detailed metabolic/immune phenotyping. RESULTS: FDG uptake in the subcutaneous adipose tissue (SAT) of the extremities (mean standardized uptake value [SUV] of the arm and leg SAT) was found to correlate with the degree of peripheral lipoatrophy (r=0.7; P=0.01). Extremity SAT FDG uptake was positively associated with homeostasis model assessment of insulin resistance (HOMA-IR; r=0.6; P=0.02) and fasting hyperinsulinaemia (r=0.7; P=0.01), while fat percentage of extremities was not. Furthermore, extremity SAT FDG uptake was significantly associated with CD4(+) T-cell count (r=0.6; P=0.05). In multivariate modelling for HOMA-IR, extremity SAT FDG uptake remained significant after controlling for body mass index and tumour necrosis factor-α (R(2) for model =0.71, P=0.02; SUV in the extremity SAT ß-estimate 12.3, P=0.009). CONCLUSIONS: In HIV lipodystrophic patients, extremity SAT FDG uptake is increased in association with reduced extremity fat and may contribute to insulin resistance. Non-invasive assessments of in situ inflammation using FDG-PET may usefully complement histological and gene expression analyses of metabolic dysregulation in peripheral fat among HIV-positive patients.
Assuntos
Extremidades/patologia , Fluordesoxiglucose F18 , Síndrome de Lipodistrofia Associada ao HIV/diagnóstico , Imagem Multimodal , Tomografia por Emissão de Pósitrons , Gordura Subcutânea/patologia , Tomografia Computadorizada por Raios X , Gordura Abdominal/metabolismo , Gordura Abdominal/patologia , Composição Corporal , Fluordesoxiglucose F18/metabolismo , Síndrome de Lipodistrofia Associada ao HIV/imunologia , Síndrome de Lipodistrofia Associada ao HIV/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Gordura Subcutânea/metabolismoRESUMO
OBJECTIVE: The aim of the study was to evaluate the interleukin-17 (IL-17) plasma level in HIV-1-infected patients and its relation to central obesity. METHODS: Eighty-four HIV-1-infected patients [42 with visceral obesity (group A) and 42 without visceral obesity (group B)] and 46 HIV-negative subjects [23 with visceral obesity (group C) and 23 without visceral obesity (group D)] were enrolled in the study. Sonographic measurements of perirenal fat diameter/body mass index (PRFD/BMI) were used to assess visceral adipose tissue thickness. RESULTS: HIV-1-infected patients had higher plasma levels of IL-17 than HIV-negative subjects [837.8 ± 260 pg/mL (mean ± standard deviation) vs. 395.3 ± 138.6 pg/mL, respectively; P<0.001]. Furthermore, HIV-1-infected patients with a diagnosis of visceral obesity had lower levels of IL-17 than HIV-infected lean patients (756.9 ± 282.9 pg/mL vs. 918.7 ± 208.4 pg/mL, respectively; P<0.01). IL-17 (r= -0.21; P=0.03) and waist circumference (r=0.48; P<0.001) were significantly associated with visceral adipose tissue thickness. A negative correlation of IL-17 (r= -0.23; P<0.001) with PRFD/BMI was found. CONCLUSIONS: This study suggests a linear negative association between IL-17 and visceral adipose tissue thickness.
Assuntos
Fármacos Anti-HIV/uso terapêutico , Soropositividade para HIV/imunologia , HIV-1/imunologia , Síndrome de Lipodistrofia Associada ao HIV/imunologia , Interleucina-17/imunologia , Obesidade Abdominal/imunologia , Adolescente , Adulto , Idoso , Índice de Massa Corporal , Estudos Transversais , Feminino , Soropositividade para HIV/complicações , Soropositividade para HIV/tratamento farmacológico , Síndrome de Lipodistrofia Associada ao HIV/tratamento farmacológico , Síndrome de Lipodistrofia Associada ao HIV/etiologia , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Obesidade Abdominal/complicações , Medição de Risco , Adulto JovemRESUMO
Highly active antiretroviral therapy (HAART) is associated with fat redistribution and metabolic disorders. The present study was undertaken to evaluate the association between peroxisome proliferator activated receptor (PPAR)α and PPARγ polymorphisms, two genes involved in lipid metabolism and adipocyte differentiation, and elements of the metabolic syndrome, lipodystrophy, or carbohydrate metabolism abnormalities in patients receiving HAART. The frequency distribution of rare alleles for PPARα (L162V) and PPARγ (P12A and H449H) was compared using the chi square test in 363 HIV-1-infected patients classified according to the presence or absence of the metabolic syndrome after 48 months of follow-up on their first PI-containing regimen. The P12A rare g allele was present in 12% patients with normal glucose metabolism, 11% patients with impaired glucose tolerance or impaired fasting glucose, and 35% patients with diabetes (p=0.014). The rare g allele for L162V was present in 14% of patients free of hypertriglyceridemia and in 7% patients with hypertriglyceridemia (p=0.04). The rare g allele for L162V was found in 15% of patients free of any sign of lipodystrophy and 8% with at least one sign of lipodystrophy (p=0.04) and the rare t allele for H449H was found in 14% of patients free of any sign of lipodystrophy and 23% of patients with at least one sign of lipodystrophy (p=0.05). There was no convincing association between any polymorphism of PPARα and PPARγ and each individual component of the metabolic syndrome, except for the relationship of the P12A polymorphism with diabetes. Confirmatory studies on a larger number of individuals are needed.
Assuntos
Terapia Antirretroviral de Alta Atividade , Soropositividade para HIV/tratamento farmacológico , Síndrome de Lipodistrofia Associada ao HIV/genética , Síndrome Metabólica/genética , PPAR alfa/genética , PPAR gama/genética , Polimorfismo Genético , Distribuição de Qui-Quadrado , Feminino , Soropositividade para HIV/genética , Soropositividade para HIV/imunologia , Síndrome de Lipodistrofia Associada ao HIV/imunologia , Humanos , Masculino , Síndrome Metabólica/imunologia , Projetos Piloto , Estudos ProspectivosRESUMO
BACKGROUND: The use of antiretroviral therapy (ART) in AIDS has been associated with lipodystrophic syndrome, which is characterized by metabolic alterations and abnormal corporal fat distribution. Our goal was to describe and evaluate the use of polymethylmethacrylate (PMMA) to treat lipoatrophy in patients with AIDS from Amazonas, Brazil. METHODS: Patients with AIDS undergoing ART and presenting with facial lipoatrophy were invited to participate in the study. A face-to-face interview was conducted, and patients were treated with applications of PMMA 30%. RESULTS: A total of 49 cases were included. The mean age was 45 (SD 6.1) years old, and the mean educational level (measured in schooling years) was 10.5 (SD 3.2) years of schooling. The median of CD4 cell count was 482.5 (interquartile range: 338-574.5) cells/mm(3) . Stavudine and zidovudine were the most frequently prescribed ART drugs. The total number of PMMA injections ranged from one to five times, and side effects were not frequent. A total of 42 (85.7%) patients reported satisfaction after a follow-up of more than 12 months, presenting good fullness of the deformity. CONCLUSIONS: Our data showed that patients with AIDS with lipoatrophy related to ART could safely benefit from PMMA-based treatment.
Assuntos
Síndrome da Imunodeficiência Adquirida/tratamento farmacológico , Terapia Antirretroviral de Alta Atividade/efeitos adversos , Síndrome de Lipodistrofia Associada ao HIV/induzido quimicamente , Síndrome de Lipodistrofia Associada ao HIV/tratamento farmacológico , Polimetil Metacrilato/uso terapêutico , Síndrome da Imunodeficiência Adquirida/imunologia , Adulto , Fármacos Anti-HIV/efeitos adversos , Fármacos Anti-HIV/uso terapêutico , Brasil , Contagem de Linfócito CD4 , Dermatoses Faciais/induzido quimicamente , Dermatoses Faciais/tratamento farmacológico , Dermatoses Faciais/virologia , Feminino , Síndrome de Lipodistrofia Associada ao HIV/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente , Polimetil Metacrilato/efeitos adversosRESUMO
OBJECTIVE: HIV-1-infected patients with lipodystrophy show insulin resistance, dyslipidemia and other signs of metabolic syndrome. Fibroblast growth factor-21 (FGF21) is a novel metabolic regulator that has been suggested to exert beneficial effects on metabolic homeostasis and insulin sensitivity. Our goal was to determine the relationship between FGF21 levels and metabolic alterations in these patients. RESEARCH DESIGN AND METHODS: Serum FGF21 levels were analyzed in 179 individuals belonging to four groups: HIV-1-infected, antiretroviral-treated patients that have developed lipodystrophy (n = 59); HIV-1-infected, antiretroviral-treated patients without lipodystrophy (n = 45); untreated (naive) HIV-1-infected patients (n = 41); and healthy control individuals (n = 34). Serum FGF21 levels were correlated with parameters indicative of altered fat distribution, metabolic and cardiovascular risk, and in relation to HIV-1 infection and antiretroviral treatment regimens. RESULTS: Serum FGF21 levels were increased in all HIV-1-infected patients, but the increases were most marked in those with lipodystrophy. FGF21 levels showed a strong positive correlation with indicators of lipodystrophy (trunk/apendicular fat ratio, waist-to-hip ratio), insulin resistance (fasting glucose, HOMA-R), dyslipidemia (low-density lipoprotein cholesterol), and liver injury (γ-glutamyltransferase). CONCLUSIONS: FGF21 levels are increased in HIV-1-infected patients, especially in those with lipodystrophy, and this increase is closely associated with insulin resistance, metabolic syndrome and makers of liver damage. Further research will be required to determine whether the increase in FGF21 levels is caused by a compensatory response or resistance to FGF21, and to establish the potential of FGF21 as a biomarker of altered metabolism in HIV-1-infected, antiretroviral-treated patients.
Assuntos
Fatores de Crescimento de Fibroblastos/metabolismo , Infecções por HIV/metabolismo , Síndrome de Lipodistrofia Associada ao HIV/metabolismo , Resistência à Insulina/fisiologia , Fígado/metabolismo , Adulto , Antropometria , Terapia Antirretroviral de Alta Atividade , Biomarcadores/metabolismo , Feminino , Fatores de Crescimento de Fibroblastos/imunologia , Infecções por HIV/imunologia , Infecções por HIV/virologia , Síndrome de Lipodistrofia Associada ao HIV/imunologia , Síndrome de Lipodistrofia Associada ao HIV/virologia , Humanos , Resistência à Insulina/imunologia , Fígado/lesões , Fígado/virologia , Masculino , Fatores de RiscoRESUMO
OBJECTIVE: Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) are involved in extracellular matrix remodelling and adipocyte differentiation and are inhibited by antiretrovirals. MMPs and TIMPs and their single nucleotide polymorphisms (SNPs) might contribute to the HAART-related lipodystrophic syndrome pathogenesis. DESIGN AND SETTING: Cross-sectional study in a university-based outpatient clinic. PATIENTS AND METHODS: Two hundred and sixteen HIV-infected patients on extended HAART were studied. Serum MMPs (1, 2, 3, 8, 9, 10, 13) and TIMPs (1, 2, 4) were measured by ELISA microarrays. MMP1 (-16071G/2G) SNP was also genotyped. Lipodystrophic syndrome was diagnosed by a clinical scale validated by fat dual energy X-ray absorptiometry. RESULTS: Eighty-two patients (38.0%) showed lipodystrophic syndrome, mostly lipoatrophy. The 2G/2G MMP1 SNP genotype was more frequent among lipodystrophic syndrome patients (41.3 vs. 20.5%, odds ratio, 2.73; 95% confidence interval, 1.41-5.29; χ² = 9.62, P = 0.002 for HIV-infected patients with and without lipodystrophic syndrome respectively). Carriers of this genotype had higher serum levels of MMP1 compared with those with the 1G/1G (P = 0.02). Higher MMP1 (P = 0.022) and lower TIMP4 (P = 0.038) serum levels were observed while comparing HIV patients with and without lipodystrophic syndrome. MMP1 2G carriage (P = 0.0008), TIMP4 lower serum levels (P = 0.02), treatment with stavudine (P < 0.0001), treatment with zidovudine (P = 0.006) and absence of hepatitis C virus coinfection (P = 0.002) were associated with lipodystrophic syndrome by logistic regression. CONCLUSION: MMP1 SNP, which induced increased serum levels of this protein, was associated with lipodystrophic syndrome.
Assuntos
Terapia Antirretroviral de Alta Atividade/efeitos adversos , HIV-1/genética , Síndrome de Lipodistrofia Associada ao HIV/genética , Metaloproteinase 1 da Matriz/genética , Polimorfismo de Nucleotídeo Único , Absorciometria de Fóton , Adulto , Contagem de Linfócito CD4 , Estudos Transversais , Ensaio de Imunoadsorção Enzimática , Feminino , Genótipo , Síndrome de Lipodistrofia Associada ao HIV/epidemiologia , Síndrome de Lipodistrofia Associada ao HIV/imunologia , Humanos , Masculino , Razão de Chances , Espanha/epidemiologiaRESUMO
Cytokines play important roles in the pathogenesis of lipodystrophy syndrome (LS). Single nucleotide polymorphisms (SNPs) at positions -607(C/A) and -137(C/G) in the promoter region of the interleukin-18 (IL-18) gene and at position +874(T/A) of the interferon-gamma (IFN-gamma) gene are related to the expression of these cytokines. To examine whether IL-18 and IFN-gamma polymorphisms are associated with LS, these SNPs were genotyped in 88 human immunodeficiency virus (HIV)-infected patients presenting LS, 79 HIV-infected without LS, and 133 healthy controls. The -607A allele, -607AA genotype, and -137G/-607A and -137C/-607A haplotypes in the IL-18 gene were over-represented in HIV patients presenting LS. The -137G/-607C haplotype was associated with protection against LS. These results indicate that the -607(C/A) SNP is associated with LS development in HIV-infected patients.
Assuntos
HIV-1 , Síndrome de Lipodistrofia Associada ao HIV/genética , Síndrome de Lipodistrofia Associada ao HIV/imunologia , Interferon gama/genética , Interleucina-18/genética , Polimorfismo de Nucleotídeo Único , Adulto , Terapia Antirretroviral de Alta Atividade/efeitos adversos , Sequência de Bases , Brasil , Estudos de Casos e Controles , Primers do DNA/genética , Feminino , Predisposição Genética para Doença , Infecções por HIV/tratamento farmacológico , Infecções por HIV/genética , Infecções por HIV/imunologia , Síndrome de Lipodistrofia Associada ao HIV/etiologia , Haplótipos , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
IL-18 is a pleiotropic and multifunctional proinflammatory cytokine that is often produced in response to a viral infection. The biological activities of the cytokine are tightly controlled by its natural antagonist, IL-18 binding protein (IL-18BP), as well as by activation of caspase-1, which cleaves the precursor form of IL-18 into its biologically mature form. The cytokine plays an important role in both innate and adaptive antiviral immune responses. Depending upon the context, it can promote TH1, TH2 and TH17 responses. Increased serum concentrations of IL-18 and concomitantly decreased concentrations of its natural antagonist have been described in HIV-infected persons as compared to HIV-seronegative healthy subjects. We discuss in this review article how increased biological activities of IL-18 contribute towards immunopathogenesis of AIDS, HIV-associated lipodystrophy syndrome and related metabolic disturbances. While the advent of potent anti-HIV drugs has significantly enhanced life span of HIV-infected patients, it has also increased the number of these patients suffering from metabolic disorders. The cytokine may prove to be a useful target for therapeutic intervention in these patients.
Assuntos
Síndrome da Imunodeficiência Adquirida/complicações , Síndrome da Imunodeficiência Adquirida/fisiopatologia , Infecções por HIV/complicações , Infecções por HIV/fisiopatologia , Síndrome de Lipodistrofia Associada ao HIV/complicações , Síndrome de Lipodistrofia Associada ao HIV/fisiopatologia , Interleucina-18/imunologia , Complexo AIDS Demência , Síndrome da Imunodeficiência Adquirida/imunologia , Animais , Terapia Antirretroviral de Alta Atividade , Doenças Cardiovasculares , Infecções por HIV/imunologia , Síndrome de Lipodistrofia Associada ao HIV/imunologia , Humanos , Resistência à Insulina , Interleucina-18/genética , Interleucina-18/metabolismo , Polimorfismo Genético/genética , Receptores de Interleucina-18/imunologia , Replicação ViralRESUMO
Before the introduction of successful antiretroviral therapy (ART), cardiovascular complications in HIV-infected patients were largely those resulting from immunosuppression (e.g. myocarditis, pericarditis, tamponade). With the advent of ART, there has been a spectacular decrease in morbidity and mortality in HIV-infected individuals. However, alongside metabolic complications caused by ART such as insulin resistance, dyslipidemia and lipodystrophy syndrome have been observed, which potentially increase the risk of cardiovascular complications, in particular coronary artery disease. Whether HIV infection and ART are independent and individual coronary risk factors is still controversial. More and more data are available demonstrating that increasing the duration of exposure to ART, and in particular protease inhibitors, increases the risk of myocardial infarction. At the same time, chronic infection, inflammation and the disruption of immune balance as a result of HIV infection itself may have the potential to alter vascular structure and function. In this article, we will review cardiovascular complications in HIV-infected patients before and after the advent of ART, focusing on coronary artery disease, its diagnosis, prognosis and therapy.
Assuntos
Antirretrovirais/uso terapêutico , Aterosclerose/complicações , Doenças Cardiovasculares/etiologia , Doença da Artéria Coronariana/complicações , Infecções por HIV/complicações , Adulto , Antirretrovirais/efeitos adversos , Aterosclerose/tratamento farmacológico , Aterosclerose/imunologia , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/imunologia , Doença da Artéria Coronariana/tratamento farmacológico , Doença da Artéria Coronariana/imunologia , Vasos Coronários/efeitos dos fármacos , Quimioterapia Combinada , Dislipidemias/imunologia , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/imunologia , HIV-1/efeitos dos fármacos , Síndrome de Lipodistrofia Associada ao HIV/imunologia , Humanos , Resistência à Insulina , Masculino , Miocardite/imunologia , Fatores de RiscoRESUMO
OBJECTIVES: To evaluate the impact on peripheral fat tissue of a nucleoside reverse transcriptase inhibitor (NRTI)-sparing regimen in lipoatrophic HIV-1 infected patients. METHODS: This 96-week prospective, randomized study compared lipoatrophic patients switched to an NRTI-sparing regimen with patients remaining on an NRTI-containing regimen. The primary endpoint was the change in thigh subcutaneous fat tissue volume between baseline and week 48, as assessed by computerized tomography. RESULTS: One hundred patients were included, 50 in each arm. At baseline, patients had been on highly active antiretroviral therapy (HAART) for a median time of 6.6 years (4.9-9.7); 71% of the patients had received thymidine analogues [stavudine (37%), zidovudine (34%)]. The mean change in fat volume between baseline and week 48 significantly favoured the NRTI-sparing arm over the NRTI-maintaining arm in the intent-to-treat analysis, with a last-observation-carried-forward approach [+34 cm(3); 95% confidence interval (CI) 5-63 cm(3); P=0.002]. This was confirmed in the intent-to-treat analysis of available data, with a mean difference of +109 cm(3) (95% CI 34-185 cm(3)) at week 96 (n=53; P=0.001). This corresponded to increases of 12 and 30% in fat volume at weeks 48 and 96, respectively, in the NRTI-sparing arm. CONCLUSIONS: Switching from an effective NRTI-containing regimen to an NRTI-sparing regimen preserves immunovirological status and increases subcutaneous fat volume at weeks 48 and 96.
Assuntos
Fármacos Anti-HIV/uso terapêutico , HIV-1 , Síndrome de Lipodistrofia Associada ao HIV/tratamento farmacológico , Síndrome de Lipodistrofia Associada ao HIV/patologia , Gordura Subcutânea/patologia , Gordura Abdominal/patologia , Adulto , Análise de Variância , Terapia Antirretroviral de Alta Atividade/métodos , Composição Corporal/efeitos dos fármacos , Contagem de Linfócito CD4 , Esquema de Medicação , Feminino , Inibidores da Protease de HIV/uso terapêutico , Síndrome de Lipodistrofia Associada ao HIV/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Inibidores da Transcriptase Reversa/uso terapêutico , Estatísticas não Paramétricas , Coxa da Perna , Carga ViralRESUMO
In this cross-sectional study, we sought to determine whether gene expression of macrophage markers and inflammatory chemokines in lipoatrophic subcutaneous abdominal adipose tissue and liver fat content are increased and interrelated in human immunodeficiency virus (HIV)-1-positive, highly active antiretroviral therapy (HAART)-treated patients with lipodystrophy (HAART+LD+; n = 27) compared with those without (HAART+LD-; n = 13). The study groups were comparable with respect to age, gender, and body mass index. The HAART+LD+ group had twofold more intra-abdominal (P = 0.01) and 1.5-fold less subcutaneous (P = 0.091) fat than the HAART+LD- group. As we have reported previously, liver fat was 10-fold higher in the HAART+LD+ compared with the HAART+LD- group (P = 0.00003). Inflammatory gene expression was increased in HAART-lipodystrophy: CD68 4.5-fold (P = 0.000013), tumor necrosis factor (TNF)-alpha 2-fold (P = 0.0094), chemokine (C-C motif) ligand (CCL) 2 2.5-fold (P = 0.0024), CCL3 7-fold (P = 0.0000017), integrin alphaM (ITGAM) 3-fold (P = 0.00067), epidermal growth factor-like module containing, mucin-like, hormone receptor-like (EMR)1 2.5-fold (P = 0.0038), and a disintegrin and metalloproteinase domain (ADAM)8 3.5-fold (P = 0.00057) higher in the HAART+LD+ compared with the HAART+LD- group. mRNA concentration of CD68 (r = 0.37, P = 0.019), ITGAM (r = 0.35, P = 0.025), CCL2 (r = 0.39, P = 0.012), and CCL3 (r = 0.54, P = 0.0003) correlated with liver fat content. In conclusion, gene expression of markers of macrophage infiltration and adipose tissue inflammation is increased in lipoatrophic subcutaneous abdominal adipose tissue of patients with HAART-associated lipodystrophy compared with those without. CD68, ITGAM, CCL2, and CCL3 expression is significantly associated with accumulation of liver fat.
Assuntos
Tecido Adiposo/patologia , Terapia Antirretroviral de Alta Atividade/efeitos adversos , HIV-1 , Síndrome de Lipodistrofia Associada ao HIV/patologia , Fígado/metabolismo , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/imunologia , Adulto , Composição Corporal/efeitos dos fármacos , Composição Corporal/imunologia , Quimiocinas/biossíntese , Quimiocinas/sangue , Quimiocinas/genética , Estudos Transversais , Citocinas/biossíntese , Citocinas/sangue , Citocinas/genética , Feminino , Expressão Gênica , Infecções por HIV/tratamento farmacológico , Infecções por HIV/imunologia , Infecções por HIV/patologia , Síndrome de Lipodistrofia Associada ao HIV/genética , Síndrome de Lipodistrofia Associada ao HIV/imunologia , Síndrome de Lipodistrofia Associada ao HIV/virologia , Humanos , Inflamação/induzido quimicamente , Inflamação/imunologia , Inflamação/patologia , Fígado/efeitos dos fármacos , Fígado/imunologia , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Masculino , RNA Mensageiro/biossíntese , RNA Mensageiro/genéticaRESUMO
We determined the IL-6 -174 G>C single nucleotide polymorphism, IL-6 mRNA expression in subcutaneous adipose tissue (SAT) and IL-6 plasma levels in HIV-1-infected patients with and without lipodystrophy and uninfected controls. HIV-1-infected patients had a greater prevalence of the IL-6 -174 C/C genotype and the C allele, higher SAT IL-6 mRNA expression and plasma IL-6 levels than controls. The IL-6 -174 G>C genotype distribution and allele frequencies, SAT IL-6 mRNA expression and IL-6 plasma levels were non-significantly different between HIV-1-infected patients with and without lipodystrophy.
Assuntos
Infecções por HIV/imunologia , HIV-1 , Síndrome de Lipodistrofia Associada ao HIV/imunologia , Interleucina-6/genética , Polimorfismo de Nucleotídeo Único , Adulto , Alelos , Fármacos Anti-HIV/uso terapêutico , Terapia Antirretroviral de Alta Atividade , Estudos de Casos e Controles , Estudos Transversais , Feminino , Frequência do Gene , Genótipo , Infecções por HIV/tratamento farmacológico , Síndrome de Lipodistrofia Associada ao HIV/tratamento farmacológico , Humanos , Interleucina-6/sangue , Masculino , Pessoa de Meia-Idade , RNA Mensageiro/análise , Gordura Subcutânea/imunologiaRESUMO
To assess the comparability of ultrasonographic (US) subcutaneous fat thickness (SFT) measurements in comparison with computed tomography (CT) at reference points (RPs) representative of HIV related adipose redistribution syndrome (HARS) in patients treated with antiretrovirals. US and CT measurements were compared in nine patients with clinical reports of HARS. We obtained the best resolution of facial (at deepest point of Bichat pad), brachial (in the dorsal face of arm) and crural SFT (at mid thigh) by means of minimal transducer pressures avoiding potential biases such as stand off pads pressure on the skin and artefacts due to too abundant quantity of gel. CT scans were obtained in the same RP where US measurements were performed such as identified by means of metallic skin markers. Median US measurement of facial SFT was 8.8 mm (95% CI: 3.1 to 13.4), 3.95 mm (95% CI: 2.62 to 5.84) for brachial SFT and 4 mm (95% CI: 3.4 to 9.4) for crural SFT. Median CT assessments of facial SFT was 8.7 mm (95% CI: 3.5 to 13.5), 4.2 mm (95% CI: 2.6 to 5.88) for brachial SFT and 5 mm (95% CI: 3.9 to 10.3) for crural SFT, with no significant difference at each RP. A linear regression showed good CT/US comparability at each RP, with no significant deviation from linearity (p > 0.10). US shows to be highly comparable with CT, excluding invaliding biases as the transducer pressure on the skin. Given the proven efficacy on the HARS assessments, if well standardized, US could be a reliable method, simpler than CT in the management of body fat changes related to HARS.
Assuntos
Síndrome de Lipodistrofia Associada ao HIV/diagnóstico por imagem , Gordura Subcutânea/diagnóstico por imagem , Adulto , Terapia Antirretroviral de Alta Atividade , Índice de Massa Corporal , Contagem de Linfócito CD4 , Face/diagnóstico por imagem , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/imunologia , Síndrome de Lipodistrofia Associada ao HIV/imunologia , Síndrome de Lipodistrofia Associada ao HIV/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Gordura Subcutânea/patologia , Tomografia Computadorizada por Raios X , UltrassonografiaRESUMO
In this cross-sectional study, we evaluate potential predictors of Metabolic Syndrome (MS) in a group of 54 Caucasian chronically HIV-infected patients with lipodystrophy. According to ATP-III criteria, 22 patients were affected by MS and 32 were not. The mean age of the sample was 41.2+/-8.6 years, and most patients were males (74.1%); the two groups were homogeneous for gender, age, viro-immunologic status and the duration of antiviral therapy. The independent association between MS and several factors including demographic characteristics, type of highly-active antiviral therapy (HAART), viro-immunologic response, common cardiovascular risk factors (including Framingham scores), and selected cytokines (IFN-gamma, TNF-alpha, IL-2, IL-4, IL-6, IL-10 and IL-18), was investigated using stepwise forward logistic regression. At multivariate analysis, the only independent predictors of the metabolic syndrome were triglycerides and IL-18. A 10 mg/dL increase in triglycerides corresponds to an adjusted risk ratio for MS of 1.11 (95 percent IC: 1.04-1.19); and patients in the top tertile of IL-18 (those with IL-18 >/= 530 pg/L) had more than three times the likelihood of MS, as compared to the bottom and medium tertiles of IL-18 (patients with IL-18< 530 pg/L). This relationship was not attenuated by the inclusion of any other variable in the multivariate model. However, the association between metabolic syndrome and IL-18 is no longer significant when IL-18 is treated as a continuous variable (trend p = 0.087). Our results on HIV patients with lipodystrophy confirm previous findings on a strong independent association between IL-18 and MS in the general population. Further research is needed to clarify the mechanism of this association and its role in the development of cardiovascular disease in HIV patients.
Assuntos
Doenças Cardiovasculares/etiologia , Infecções por HIV/complicações , Síndrome Metabólica/etiologia , Adulto , Fármacos Anti-HIV/administração & dosagem , Fármacos Anti-HIV/uso terapêutico , Terapia Antirretroviral de Alta Atividade , Doenças Cardiovasculares/diagnóstico , Estudos Transversais , Citocinas/sangue , Citocinas/imunologia , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/imunologia , Infecções por HIV/metabolismo , Síndrome de Lipodistrofia Associada ao HIV/etiologia , Síndrome de Lipodistrofia Associada ao HIV/imunologia , Síndrome de Lipodistrofia Associada ao HIV/metabolismo , Humanos , Metabolismo dos Lipídeos , Masculino , Síndrome Metabólica/imunologia , Síndrome Metabólica/metabolismo , Prognóstico , Risco , Triglicerídeos/sangue , Carga ViralRESUMO
OBJECTIVES: Clinical disorders occurring in HIV-infected patients on antiretroviral therapy (ART) have been linked to mitochondrial dysfunction, for example, lactic acidosis and lipodystrophy. Mitochondrial membrane potential (delta psi m) is the most direct measure of the state of energization of the mitochondria. We analysed delta psi m, of peripheral blood mononuclear cells (PBMCs) in HIV-negative, healthy subjects (n=8), HIV-infected, treatment-naive patients (n=30), and HIV-infected patients on ART (n=58). The influence of ART was analysed in six patients who started their first regimen. METHODS: The delta psi m of PBMC was measured by flow cytometry using the dye JC-1. RESULTS: The delta psi m was significantly lower in HIV-infected patients than in HIV-negative controls. This difference was detected in both treated (P = 0.0001) and untreated patients (P = 0.001). The delta psi m of PBMCs was highly correlated with CD4+ T-cell count in therapy-naive patients (P = 0.002, r = 0.546) and in treated patients (P = 0.028, r = 0.288). The delta psi m increased significantly in therapy-naive patients after starting ART (P = 0.001). Patients with lipoatrophy had significantly lower delta psi m than patients without lipodystrophy or with lipohypertrophy (P = 0.023). CONCLUSIONS: In HIV-infected persons delta psi m is significantly reduced. Patients with lipoatrophy have significantly reduced delta psi m. This is the first study showing that the delta psi m of PBMCs is highly correlated with CD4+ T-cell count in HIV infection.