RESUMO
BACKGROUND: The aim of this study was to establish the prevalence of lipodystrophy and its association to cumulative exposure to antiretroviral drugs. METHOD: We conducted a cross sectional study in all HIV- infected patients attending the HIV clinic in the Centre hospitalier universitaire de Montréal (CHUM) with DEXA scan. Lipodystrophy was defined as a trunk/limb fat ratio ≥ 1.5. Association between cumulative exposure to antiretroviral (measured in years of use) with trunk/limb fat ratio (coded as a continuous variable) was assessed using univariate and multivariate linear regression for each antiretroviral drug with at least 40 exposed patients. RESULTS: One hundred sixty-six patients were included. Seventy-five percent were male, median age was 56 years, 67% were Caucasian. Overall, prevalence of lipodystrophy was 47%, with a mean trunk/limb fat ratio of 1.87, SD = 1.03, min = 0.6 and max = 5.87. Each 10-year increase in age and HIV infection duration was associated with an average increase of 0.24 and 0.34 for the trunk/limb fat ratio respectively. (p = 0.003, p = 0.002, respectively) Patients classified as lipodystrophic were more likely to be diabetic (50 vs. 28%, p = 0.07) and to have dyslipidemia (47 vs. 19%, p = 0.01). According to viral load at DEXA test, each one log increase was associated with less probability (0.7) of lipodystrophy. (p = 0.01) Among ARV drugs tested, there was an association between years of use of d4T, ritonavir and raltegravir and higher trunk/limb fat ratio (indicating more lipodystrophy) (p < 0.05). CONCLUSION: Lipodystrophy is very common in HIV infected patients and is correlated with duration of some new antiretroviral drugs.
Assuntos
Antirretrovirais/uso terapêutico , Infecções por HIV/tratamento farmacológico , Síndrome de Lipodistrofia Associada ao HIV/diagnóstico , Absorciometria de Fóton , Adulto , Idoso , Estudos Transversais , Dislipidemias/diagnóstico , Dislipidemias/etiologia , Feminino , Síndrome de Lipodistrofia Associada ao HIV/epidemiologia , Síndrome de Lipodistrofia Associada ao HIV/etiologia , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Carga ViralRESUMO
INTRODUCTION: Lipodystrophy syndrome associated with highly active antiretroviral therapy (HAART) may lead to low self-esteem and poor compliance with the drug treatment on patients infected with human immunodeficiency virus (HIV), which is a matter of concern for the health system. The aim of this study was to evaluate patients with HIV submitted to gluteal augmentation with intramuscular silicone implants to correct gluteal lipoatrophy related to the use of HAART. METHODS: This is a retrospective evaluation of 10 patients submitted to gluteal augmentation with intramuscular silicone implant for correction of gluteal lipoatrophy related to the use of HAART, operated between 2012 and 2015. Postoperative complications and the degree of patient's satisfaction were analyzed. RESULTS: There were 3 postoperative complications including 1 case of surgical wound dehiscence and 2 cases of seroma. Six months after surgery, 8 patients had an excellent degree of satisfaction, and 2 patients had a good degree of satisfaction related to the procedure. Although this intervention does not offer functional advantages, it improves the body contour, increases patients' self-esteem, and helps them to accept their body image. These advantages can lead to higher compliance with prolonged HAART. CONCLUSIONS: Gluteal augmentation with intramuscular silicone implant can be a viable option to treat patients with HIV with gluteal lipoatrophy related to the use of HAART. The patients were satisfied with the outcomes of the procedure, and there were only minor self-limited postoperative complications.
Assuntos
Terapia Antirretroviral de Alta Atividade/efeitos adversos , Nádegas/cirurgia , Síndrome de Lipodistrofia Associada ao HIV/cirurgia , Próteses e Implantes , Géis de Silicone , Adulto , Estética , Feminino , Infecções por HIV/diagnóstico , Infecções por HIV/tratamento farmacológico , Síndrome de Lipodistrofia Associada ao HIV/etiologia , Síndrome de Lipodistrofia Associada ao HIV/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente , Implantação de Prótese/métodos , Estudos Retrospectivos , Estudos de Amostragem , Cirurgia Plástica/métodos , Resultado do TratamentoAssuntos
Infecções por HIV/terapia , Infecções por HIV/transmissão , Algoritmos , Antirretrovirais/uso terapêutico , Densidade Óssea , Relação CD4-CD8 , Doenças Cardiovasculares/etiologia , Criança , Dislipidemias/etiologia , Diagnóstico Precoce , Feminino , Infecções por HIV/diagnóstico , Infecções por HIV/epidemiologia , Síndrome de Lipodistrofia Associada ao HIV/etiologia , Humanos , Transmissão Vertical de Doenças Infecciosas , Resistência à Insulina , Gravidez , Latência Viral/imunologiaRESUMO
This study attempts to provide a concrete understanding to the embodied experience of HIV/AIDS. PLWHA have to cope with physical changes, especially lipodystrophy, caused by HIV and its treatment. These clinical manifestations make the disease socially visible and form a potential source of stigmatization. Visibility seems to transform the personal experience of this particular illness into a collective one. The changing body image and the stigma, which is often internalized by individuals, along with other consequences of chronic illness, such as alteration of life plans and social relationships, constitute new elements that appear in their life after diagnosis. These new experiences can break one's biographical continuity, especially in cases like HIV/AIDS. Semi-structured and in-depth interviews were conducted with 18 HIV-positive individuals (13 men, 5 women) with lipodystrophy. Their ages ranged from 36 to 65 years. The analysis of data revealed three main themes: loss of control over the body, ambivalence about visibility of HIV/AIDS, attributing positive meaning to HIV/AIDS. Physical changes caused by lipodystrophy are a source of dysphoria for PLWHA. This dissatisfaction was closely associated with the absence of control over their own body, due to the virus and the side effects of medication. Furthermore, it became evident that there was ambivalence among participants about the visibility of HIV, as it was in parallel a source of stigmatization, but also a part of their identity and biography. Results indicate that individuals were in search of meaning and constitute strategies in order to "answer" to the disruptive aspects of HIV. These were the normalization of illness, the integration into personal identity and the recognition of positive effects of HIV in their lives (e.g., stopping drug and alcohol abuse). Further research is required to identify the factors that determine the selection of each "answer" by these particular individuals who belong to broader social groups.
Assuntos
Adaptação Psicológica , Imagem Corporal , Infecções por HIV/complicações , Infecções por HIV/psicologia , Síndrome de Lipodistrofia Associada ao HIV/psicologia , Estigma Social , Adolescente , Adulto , Idoso , Antirretrovirais/uso terapêutico , Feminino , Infecções por HIV/tratamento farmacológico , Síndrome de Lipodistrofia Associada ao HIV/etiologia , Síndrome de Lipodistrofia Associada ao HIV/cirurgia , Humanos , Entrevistas como Assunto , Masculino , Pessoa de Meia-Idade , Preconceito , Pesquisa Qualitativa , EstereotipagemRESUMO
BACKGROUND: Lipoatrophy of the face negatively impacts the quality of life and body image of individuals on antiretroviral therapy. Facial fillers can minimize the stigma associated with the human immonodeficiency virus (HIV). OBJECTIVES: In this 5-year follow-up study, the author assessed the safety and efficacy of a permanent, non-biodegradable, polyacrylamide hydrogel for facial volume restoration, and compared the results with those of a previous 18-month follow-up study. METHODS: Thirty-one HIV-positive individuals, initially enrolled in the study between January 2008 and January 2009, received treatment of facial wasting by injection of the polyacrylamide gel until complete volume restoration was achieved. Asepsis rules were strictly observed before and during each injection session. Patients evaluated their aesthetic outcomes on a visual analog scale. RESULTS: Patient satisfaction was high. There was no occurrence of local infection, foreign-body reaction, or product during the 5 years of follow-up. Small, palpable, nonvisible nodules were recorded in nine cases. It appears that these same nodules were present in the 18-month study. It is believed that the nodules were caused by overfilling in the same site. CONCLUSIONS: As supported by the initial 18-month study, polyacrylamide hydrogel filler appears safe and effective for the treatment of HIV-related lipoatrophy. With strict observation of asepsis rules and patient adherence to posttreatment instructions, this filler can be ideal for treating facial wasting in patients with HIV. LEVEL OF EVIDENCE: 3 Therapeutic.
Assuntos
Resinas Acrílicas/uso terapêutico , Antivirais/efeitos adversos , Infecções por HIV/complicações , Síndrome de Lipodistrofia Associada ao HIV/reabilitação , Qualidade de Vida , Resinas Acrílicas/efeitos adversos , Adulto , Assistência Ambulatorial/métodos , Antivirais/uso terapêutico , Técnicas Cosméticas , Estética , Face , Feminino , Seguimentos , Infecções por HIV/diagnóstico , Infecções por HIV/tratamento farmacológico , Síndrome de Lipodistrofia Associada ao HIV/etiologia , Síndrome de Lipodistrofia Associada ao HIV/psicologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
BACKGROUND: Many HIV antiretroviral medications have been associated with chronic liver injury. HIV-infected patients frequently develop HIV and highly active antiretroviral treatment-associated lipodystrophy syndrome (HALS), characterized by accumulation of intra-abdominal fat, insulin resistance, and hepatic steatosis. We sought to determine whether long-term exposure to specific antiretroviral medications or the presence of HALS predispose HIV-infected patients to the development of cirrhosis. METHODS: HIV-infected patients with cirrhosis who received care in the Veterans Affairs Healthcare System nationally in 2009 were matched by hepatitis C virus (HCV) coinfection status and year of first visit for HIV to the Veterans Affairs Healthcare System with HIV-infected patients without cirrhosis in a 1 : 3 ratio. RESULTS: Among HIV/HCV coinfected patients (593 with cirrhosis and 1591 matched controls), HALS was associated with a significantly increased risk for cirrhosis (adjusted odds ratio 1.6, 95% confidence interval 1.1-2.3), especially among Black patients (adjusted odds ratio 2.9, 95% confidence interval 1.6-5.2). In addition, among HIV/HCV coinfected patients, longer cumulative exposures to all antiretroviral medications, all nucleoside reverse transcriptase inhibitors, all protease inhibitors, and selected individual medications (didanosine, stavudine, and nelfinavir) were found to be significantly associated with cirrhosis. In contrast, among HIV-infected patients not coinfected with HCV (245 with cirrhosis and 658 matched controls), HALS or exposure to antiretroviral medications was found not to be significantly associated with cirrhosis, with the exception of didanosine. CONCLUSION: HALS and cumulative exposure to nucleoside reverse transcriptase inhibitors and protease inhibitors, especially stavudine, didanosine, and nelfinavir, were found to be associated with the development of cirrhosis in HIV/HCV coinfected patients, but not in HIV-monoinfected patients.
Assuntos
Coinfecção/epidemiologia , Infecções por HIV/tratamento farmacológico , Síndrome de Lipodistrofia Associada ao HIV/epidemiologia , Hepatite C/epidemiologia , Cirrose Hepática/epidemiologia , Adulto , Idoso , Terapia Antirretroviral de Alta Atividade/efeitos adversos , Estudos de Casos e Controles , Didanosina/uso terapêutico , Feminino , Infecções por HIV/complicações , Inibidores da Protease de HIV/uso terapêutico , Síndrome de Lipodistrofia Associada ao HIV/etnologia , Síndrome de Lipodistrofia Associada ao HIV/etiologia , Hispânico ou Latino/estatística & dados numéricos , Humanos , Cirrose Hepática/etnologia , Masculino , Pessoa de Meia-Idade , Nelfinavir/uso terapêutico , Inibidores da Transcriptase Reversa/uso terapêutico , Fatores de Risco , Estavudina/uso terapêutico , Fatores de TempoAssuntos
Terapia Antirretroviral de Alta Atividade , Cardiomiopatias/etiologia , Infecções por HIV/tratamento farmacológico , Síndrome de Lipodistrofia Associada ao HIV/etiologia , Disfunção Ventricular Esquerda/etiologia , Função Ventricular Esquerda , Terapia Antirretroviral de Alta Atividade/efeitos adversos , Cardiomiopatias/diagnóstico , Cardiomiopatias/metabolismo , Estudos de Casos e Controles , Infecções por HIV/complicações , Infecções por HIV/diagnóstico , Síndrome de Lipodistrofia Associada ao HIV/diagnóstico , Síndrome de Lipodistrofia Associada ao HIV/metabolismo , Humanos , Imageamento por Ressonância Magnética , Espectroscopia de Ressonância Magnética , Contração Miocárdica , Miocárdio/química , Valor Preditivo dos Testes , Fatores de Risco , Resultado do Tratamento , Triglicerídeos/análise , Disfunção Ventricular Esquerda/diagnóstico , Disfunção Ventricular Esquerda/fisiopatologiaRESUMO
OBJECTIVE: To evaluate the changes of body composition in male patients with human immunodeficiency (HIV)-related lipodystrophy (LD) syndrome (HIV-LD) switching from stavudine (d4T) to zidovudine (AZT) or tenofovir (TDF) by Dual-energy X-ray absorptiometry (DXA). METHODS: A total of 47 men with HIV-LD who had been exposed to stavudine (d4T) were enrolled in our study from May 2007 to September 2013 in Peking Union Medical College Hospital. Twice DXA assessments were administrated with interval of at least 12 months. All patients were divided into two different treatment regimens, either AZT group switching from d4T to zidovudine (AZT) or TDF group switching from d4T to TDF. Parameters of body composition in two groups were evaluated by DXA. RESULTS: Compared with baseline level, lower limb lean mass increased significantly after treatment [(15.4 ± 1.7) kg vs (16.0 ± 1.7) kg, t = 2.781, P < 0.01] and lower limb fat mass had a small decrease(P = 0.05) in AZT group. In TDF group, there were significant increases both in upper limb fat mass [(0.6 ± 0.3) kg vs (1.0 ± 0.7) kg, t = 2.422, P < 0.05] and lower limb fat mass [(1.8 ± 0.8) kg vs (2.6 ± 1.7) kg, t = 2.369, P < 0.05]. In AZT group, change of lower limb fat mass was generally small (median -0.04 kg, -4.55%). In TDF group, increase of lower limb fat mass and percentage of lower limb fat gain were even greater (median 0.46 kg, 27.41%). In a visual comparison of DXA results between AZT and TDF recipients, more fat gain of leg fat mass was seen in patients who switched from d4T to TDF (U = 2.954, P < 0.01). CONCLUSIONS: Compared with AZT group, TDF group led to a more increase in leg fat mass. Replacing d4T with TDF translates into an improvement of lipodystrophy. Although fat mass did not show a significant increase in AZT group, lean mass had improved after switching treatment, indicating AZT as a possible alternative agent of d4T. Body composition in men patients with HIV-LD can help to adjust the treatment regimen.
Assuntos
Absorciometria de Fóton , Antivirais/uso terapêutico , Composição Corporal , Infecções por HIV/tratamento farmacológico , Síndrome de Lipodistrofia Associada ao HIV/diagnóstico por imagem , Adenina/análogos & derivados , Fármacos Anti-HIV , Síndrome de Lipodistrofia Associada ao HIV/etiologia , Humanos , Masculino , Organofosfonatos , Estavudina , Tenofovir , ZidovudinaRESUMO
Optimal nutrition is an important part of human immunodeficiency virus (HIV) care; to support the immune system, limit HIV-associated complications as well as maintain better quality of life and survival. The presentation and nature of malnutrition in patients with HIV has changed dramatically over the past 30 years from predominantly a wasting syndrome to lipodystrophy and, now, frailty. Nevertheless, we continue to see all 3 presentations in patient care today. The pathogenesis of poor nutrition in HIV-infected patients depends on caloric intake, intestinal nutrient absorption/translocation, and resting energy expenditure, which are features seen in all chronic diseases.
Assuntos
Infecções por HIV/complicações , Síndrome de Emaciação por Infecção pelo HIV/etiologia , Estado Nutricional , Obesidade/etiologia , Terapia Antirretroviral de Alta Atividade , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Síndrome de Emaciação por Infecção pelo HIV/dietoterapia , Síndrome de Emaciação por Infecção pelo HIV/epidemiologia , HIV-1 , Síndrome de Lipodistrofia Associada ao HIV/epidemiologia , Síndrome de Lipodistrofia Associada ao HIV/etiologia , Síndrome de Lipodistrofia Associada ao HIV/terapia , Humanos , Distúrbios Nutricionais/epidemiologia , Distúrbios Nutricionais/etiologia , Obesidade/epidemiologiaRESUMO
Alcohol abuse is the most common and costly form of drug abuse in the United States. It is well known that alcohol abuse contributes to risky behaviors associated with greater incidence of human immunodeficiency virus (HIV) infections. As HIV has become a more chronic disease since the introduction of antiretroviral therapy, it is expected that alcohol use disorders will have an adverse effect on the health of HIV-infected patients. The biomedical consequences of acute and chronic alcohol abuse are multisystemic. Based on what is currently known of the comorbid and pathophysiological conditions resulting from HIV infection in people with alcohol use disorders, chronic alcohol abuse appears to alter the virus infectivity, the immune response of the host, and the progression of disease and tissue injury, with specific impact on disease progression. The combined insult of alcohol abuse and HIV affects organ systems, including the central nervous system, the immune system, the liver, heart, and lungs, and the musculoskeletal system. Here we outline the major pathological consequences of alcohol abuse in the HIV-infected individual, emphasizing its impact on immunomodulation, erosion of lean body mass associated with AIDS wasting, and lipodystrophy. We conclude that interventions focused on reducing or avoiding alcohol abuse are likely to be important in decreasing morbidity and improving outcomes in people living with HIV/AIDS.
Assuntos
Alcoolismo/complicações , Infecções por HIV/complicações , Infecções por HIV/imunologia , Complexo AIDS Demência/etiologia , Complexo AIDS Demência/patologia , Progressão da Doença , Transmissão de Doença Infecciosa , HIV , Infecções por HIV/epidemiologia , Infecções por HIV/transmissão , Síndrome de Lipodistrofia Associada ao HIV/etiologia , Síndrome de Lipodistrofia Associada ao HIV/patologia , Humanos , Assunção de Riscos , Estados Unidos/epidemiologiaRESUMO
INTRODUCTION: With the introduction of combination antiretroviral therapy (ART) for HIV infection in the mid-1990s, descriptions of morphological changes and metabolic disturbances in treated patients began to emerge. HIV-1/highly active ART-associated lipodystrophy syndrome (HALS) involves metabolic abnormalities and diverse forms of anomalous fat distribution. The current review focuses on the pathophysiological basis and the clinical evidence for the use of several medical strategies in the management of HALS. AREAS COVERED: We have covered the most relevant studies related to the pharmacological strategies in the treatment of HALS, with attention to the current and novel antiretroviral agents. EXPERT OPINION: The most commonly used strategies for HALS reversion have included modification of host-dependent factors, including those related to HIV-1 infection and those associated with ART. Preventive and medical strategies have been associated with moderate success. The only intervention that offers an immediate aesthetical improvement for patients with HALS so far has been plastic surgery.
Assuntos
Antirretrovirais/uso terapêutico , HIV-1/efeitos dos fármacos , Síndrome de Lipodistrofia Associada ao HIV/tratamento farmacológico , Adiposidade/efeitos dos fármacos , Animais , Antirretrovirais/efeitos adversos , Terapia Antirretroviral de Alta Atividade/efeitos adversos , HIV-1/isolamento & purificação , Síndrome de Lipodistrofia Associada ao HIV/diagnóstico , Síndrome de Lipodistrofia Associada ao HIV/etiologia , Síndrome de Lipodistrofia Associada ao HIV/fisiopatologia , Hormônios/uso terapêutico , HumanosRESUMO
In the absence of a cure, HIV-infected patients are being successfully treated with antiretroviral therapies (ART) and living longer. Indeed, an increasing number of HIV-infected patients are living beyond the age of 50 years, and in that regard, the use of ART has transformed HIV into a chronic medical condition. As more HIV-infected patients are virologically controlled and living longer, the trajectory of disease morbidity has shifted, however, primarily from opportunistic infections and immune dysfunction to metabolic complications. Evidence suggests that HIV-infected patients acquire significant metabolic risks, including lipodystrophic changes, subclinical atherosclerosis, and insulin resistance. The etiology of these metabolic complications specifically in HIV-infected patients is not entirely clear but may be related to a complex interaction between long-term consequences of infection and HIV itself, chronic use of antiretrovirals, and underlying inflammatory processes. Previous classes of ART, such as protease inhibitors (PIs) and reverse transcriptase inhibitors, have been implicated in altering fat redistribution and lipid and glucose homeostasis. Advances in drug development have introduced newer ART with strategies to target novel mechanisms of action and improve patient adherence with multi-class drug combinations. In this review, we will focus on these newer classes of ART, including selected entry inhibitors, integrase inhibitors, and multi-class drug combinations, and two newer PIs, and the potential of these newer agents to cause metabolic complications in HIV-infected patients. Taken together, further reduction of morbidity in HIV-infected patients will require increasing awareness of the deleterious metabolic complications of ART with subsequent management to mitigate these risks.
Assuntos
Fármacos Anti-HIV/efeitos adversos , Composição Corporal/efeitos dos fármacos , Infecções por HIV/tratamento farmacológico , HIV/efeitos dos fármacos , Resistência à Insulina , Metabolismo dos Lipídeos/efeitos dos fármacos , Animais , Fármacos Anti-HIV/uso terapêutico , Terapia Antirretroviral de Alta Atividade/efeitos adversos , Aterosclerose/etiologia , Aterosclerose/prevenção & controle , HIV/crescimento & desenvolvimento , HIV/imunologia , HIV/metabolismo , Infecções por HIV/imunologia , Infecções por HIV/patologia , Infecções por HIV/fisiopatologia , Síndrome de Lipodistrofia Associada ao HIV/etiologia , Síndrome de Lipodistrofia Associada ao HIV/prevenção & controle , HumanosRESUMO
OBJECTIVES: A relationship between obesity and intestinal bacterial translocation has been reported. Very little information is available with respect to the involvement of the bacterial translocation mechanistic pathway in HIV-1/highly active antiretroviral therapy (HAART)-associated lipodystrophy syndrome (HALS). We determined whether lipopolysaccharide (LPS)-binding protein (LBP), cluster of differentiation 14 (CD14), myeloid differentiation protein 2 (MD2) and toll-like receptor 4 (TLR4) single-nucleotide polymorphisms and LPS, LBP and soluble CD14 (sCD14) plasma levels are involved in HALS. PATIENTS AND METHODS: This cross-sectional multicentre study involved 558 treated HIV-1-infected patients, 240 with overt HALS and 318 without HALS. Anthropometric, clinical, immunovirological and metabolic variables were determined. Polymorphisms were assessed by genotyping. Plasma levels were determined by ELISA in 163 patients (81 with HALS and 82 without HALS) whose stored plasma samples were available. Student's t-test, one-way ANOVA, two-way repeated measures ANOVA, the χ(2) test and Pearson and Spearman correlation analyses were carried out for statistical analysis. RESULTS: LBP rs2232582 TâC polymorphism was significantly associated with HALS (Pâ=â0.01 and Pâ=â0.048 for genotype and allele analyses, respectively). Plasma levels of LPS (Pâ=â0.009) and LBP (Pâ<â0.001) were significantly higher and sCD14 significantly lower (Pâ<â0.001) in patients with HALS compared with subjects without HALS. LPS levels were independently predicted by triglycerides (Pâ<â0.001) and hepatitis C virus (Pâ=â0.038), LBP levels by HALS (Pâ<â0.001) and sCD14 levels by age (Pâ=â0.008), current HIV-1 viral load (Pâ=â0.001) and protease inhibitor use (Pâ=â0.018). CONCLUSIONS: HALS is associated with LBP polymorphism and with higher bacterial translocation.
Assuntos
Proteínas de Fase Aguda/metabolismo , Proteínas de Transporte/metabolismo , Síndrome de Lipodistrofia Associada ao HIV/etiologia , Síndrome de Lipodistrofia Associada ao HIV/metabolismo , Receptores de Lipopolissacarídeos/metabolismo , Lipopolissacarídeos/imunologia , Antígeno 96 de Linfócito/metabolismo , Glicoproteínas de Membrana/metabolismo , Transdução de Sinais , Receptor 4 Toll-Like/metabolismo , Proteínas de Fase Aguda/genética , Adulto , Terapia Antirretroviral de Alta Atividade/efeitos adversos , Contagem de Linfócito CD4 , Proteínas de Transporte/sangue , Proteínas de Transporte/genética , Estudos de Casos e Controles , Estudos Transversais , Feminino , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Infecções por HIV/imunologia , Infecções por HIV/virologia , HIV-1 , Síndrome de Lipodistrofia Associada ao HIV/diagnóstico , Humanos , Inflamação , Receptores de Lipopolissacarídeos/sangue , Receptores de Lipopolissacarídeos/genética , Lipopolissacarídeos/sangue , Antígeno 96 de Linfócito/genética , Masculino , Glicoproteínas de Membrana/sangue , Glicoproteínas de Membrana/genética , Pessoa de Meia-Idade , Fatores de Risco , Receptor 4 Toll-Like/genética , Carga ViralRESUMO
In the late 1990s, reports of unusual changes in body fat distribution named 'lipodystrophy' (LD) began to appear in HIV patients mitigating the enormous enthusiasm about improvement of survival and quality of life provided by the combinations of antiretroviral (ARV) drug classes, the so-called highly active antiretroviral therapy (HAART), which had just become available at that time. The objective of this paper is to critically review the literature on LD and to discuss the impact of newer ARV agents, namely atazanavir, darunavir and raltegravir, as well as strategies of the late HAART era, including single-tablet regimens and nucleoside-sparing regimens. Studies in which LD was measured by dual-energy x-ray absorptiometry or by abdominal computed tomography or magnetic resonance imaging scan only, were included. We were unable to identify studies depicting a negative impact of drugs or ARV regimens on limb fat loss. On the contrary, a few studies identified a negative impact of atazanavir/ritonavir or darunavir/ritonavir on trunk fat increase. It should be noted that this anthropometric measure is a poor instrument since it cannot distinguish between subcutaneous and visceral fat. We conclude that presumably the body fat changes currently observed in HIV-infected patients is the net result of competing phenomena: on one side the natural history of lipohypertrophy as a result of HIV and HAART impact, and on the other side the physiological body fat changes observed in the aging population.
Assuntos
Envelhecimento , Antirretrovirais/efeitos adversos , Síndrome de Lipodistrofia Associada ao HIV/prevenção & controle , Oligopeptídeos/efeitos adversos , Piridinas/efeitos adversos , Pirrolidinonas/efeitos adversos , Sulfonamidas/efeitos adversos , Adiposidade/efeitos dos fármacos , Antirretrovirais/administração & dosagem , Antirretrovirais/uso terapêutico , Terapia Antirretroviral de Alta Atividade/efeitos adversos , Sulfato de Atazanavir , Darunavir , Combinação de Medicamentos , Infecções por HIV/tratamento farmacológico , Infecções por HIV/fisiopatologia , Inibidores de Integrase de HIV/administração & dosagem , Inibidores de Integrase de HIV/efeitos adversos , Inibidores de Integrase de HIV/uso terapêutico , Inibidores da Protease de HIV/administração & dosagem , Inibidores da Protease de HIV/efeitos adversos , Inibidores da Protease de HIV/uso terapêutico , Síndrome de Lipodistrofia Associada ao HIV/etiologia , Síndrome de Lipodistrofia Associada ao HIV/metabolismo , Síndrome de Lipodistrofia Associada ao HIV/terapia , Humanos , Nucleosídeos/metabolismo , Oligopeptídeos/administração & dosagem , Oligopeptídeos/uso terapêutico , Piridinas/administração & dosagem , Piridinas/uso terapêutico , Pirrolidinonas/administração & dosagem , Pirrolidinonas/uso terapêutico , Raltegravir Potássico , Ensaios Clínicos Controlados Aleatórios como Assunto , Inibidores da Transcriptase Reversa/administração & dosagem , Inibidores da Transcriptase Reversa/efeitos adversos , Inibidores da Transcriptase Reversa/uso terapêutico , Sulfonamidas/administração & dosagem , Sulfonamidas/uso terapêuticoRESUMO
The use of highly active antiretroviral therapy (HAART) in the treatment of human immunodeficiency virus has dramatically altered both the landscape of this disease and the prognosis for those affected. With more patients now receiving HAART, adverse effects such as lipodystrophy and metabolic syndrome have emerged. In HIV/HAART-associated lipodystrophy syndrome (HALS), patients demonstrate fat maldistribution with dyslipidemia, insulin resistance, and other metabolic complications. Recent studies have contributed to the elucidation of the pathophysiological abnormalities seen in this syndrome and have provided guidance for the study and use of potential treatments for these patients, but widely accepted guidelines have not yet been established. Two adipokines, leptin and adiponectin, are decreased in patients with HALS and lipoatrophy or lipodystrophy. Further, recent proof-of-concept clinical trials have proven the efficacy of leptin replacement and medications that increase circulating adiponectin levels in improving the metabolic profile of HALS patients. This review article highlights recent evidence on leptin replacement and compares leptin's efficacy to that of other treatments, including metformin and thiazolidinediones, on metabolic abnormalities such as impaired insulin-glucose homeostasis associated with lipodystrophy in patients receiving HAART. It is hoped that forthcoming large phase III clinical trials will allow the addition of leptin to our therapeutic armamentarium for use in patients suffering from this disease state.
Assuntos
Adiponectina/uso terapêutico , Síndrome de Lipodistrofia Associada ao HIV/tratamento farmacológico , Leptina/uso terapêutico , Adiponectina/fisiologia , Intolerância à Glucose/tratamento farmacológico , Síndrome de Lipodistrofia Associada ao HIV/etiologia , Humanos , Leptina/fisiologia , Metformina/uso terapêutico , Tiazolidinedionas/uso terapêuticoRESUMO
Studies suggest that mitochondrial DNA (mtDNA) haplogroups are associated with antiretroviral therapy (ART)-related metabolic complications and distal sensory polyneuropathy (DSP), but there have been few studies in persons of African descent. We explored such associations in South African adults. Clinical and laboratory data and DNA specimens from a cross-sectional study were used. Sequencing and Phylotree determined African mtDNA subhaplogroups. Wilcoxon and regression analyses determined associations between mtDNA subhaplogroups and ART-related complications. The 171 participants represented six major haplogroups: L0 (n=78), L1 (n=3), L2 (n=30), L3 (n=53), L4 (n=1), and L5 (n=6). Analyses were restricted to 161 participants representing L0, L2, and L3: 78% were female; the median age was 36 years. All had been exposed to thymidine analogues, 42% were on lopinavir/ritonavir (lopinavir/r), and 58% were on either efavirenz or nevirapine. Median (IQR) ART duration was 22 (14-36) months. Median fasting triglycerides were 1.60 (1.13-1.75) and 1.04 (0.83-1.45) mmol/liter among L3e1 (n=22) and other subhaplogroups, respectively (p=0.003). Subhaplogroup L3e1 [adjusted OR (aOR) 3.16 (95% CI: 1.11-8.96); p=0.03] and exposure to lopinavir/r [aOR 2.98 (95% CI: 1.02-8.96); p=0.05] were independently associated with hypertriglyceridemia, after adjusting for age, sex, and ART duration. There were no significant associations between mtDNA haplogroups and cholesterol, dysglycemia, hyperlactatemia, or lipoatrophy, or DSP. Subhaplogroup L3e1 and lopinavir/r exposure were independently associated with hypertriglyceridemia in black South Africans on ART. This is the first report to link an African mtDNA variant with hypertriglyceridemia. If replicated, these findings may provide new insights into host factors affecting metabolic complications.
Assuntos
Fármacos Anti-HIV/efeitos adversos , DNA Mitocondrial/genética , Infecções por HIV/tratamento farmacológico , Infecções por HIV/genética , Doenças Metabólicas/etiologia , Doenças Metabólicas/genética , Adulto , População Negra/genética , Estudos Transversais , Feminino , Predisposição Genética para Doença , Variação Genética , Genoma Mitocondrial , Infecções por HIV/complicações , Síndrome de Lipodistrofia Associada ao HIV/etiologia , Síndrome de Lipodistrofia Associada ao HIV/genética , Humanos , Hipertrigliceridemia/etiologia , Hipertrigliceridemia/genética , Masculino , Projetos Piloto , Polineuropatias/etiologia , Polineuropatias/genética , África do SulRESUMO
BACKGROUND: To determine the role of fibroblast growth factor (FGF)-19 and FGF21 and the endocrine FGFs receptor system in the metabolic alterations that manifest in HIV-1-infected patients undergoing highly active antiretroviral treatment (HAART). METHODS: Serum FGF19 and FGF21 levels were determined in 4 groups of individuals as follows: (1) HIV-1-infected HAART patients with lipodystrophy (n = 38); or (2) without lipodystrophy (n = 34); (3) untreated (naive) HIV-1-infected patients (n = 34); and (4) healthy controls (n = 31). Serum FGF19 levels were correlated with anthropometric, metabolic, HIV-1 infection-related, and HAART-related parameters and with FGF21 levels. The gene expression of FGF receptor 1 and the coreceptor ß-Klotho was analyzed in adipose tissue from 10 individuals from each group. RESULTS: Serum FGF19 levels were significantly reduced in all groups of HIV-1-infected patients, whereas FGF21 levels were increased. FGF19 levels were negatively correlated with insulin resistance and insulin levels and positively correlated with high-density lipoprotein cholesterol. FGF19 was inversely correlated with cumulative exposure to nucleoside reverse transcriptase inhibitor and nonnucleoside reverse transcriptase inhibitor drugs. The expression of FGF receptor 1 and coreceptor ß-Klotho was reduced in adipose tissue from all groups of HIV-infected patients. CONCLUSIONS: FGF19 levels are reduced in HIV-1-infected patients, in contrast with FGF21 levels. Impaired expression of the corresponding receptor and coreceptor, which mediate the actions of endocrine FGFs in adipose tissue, suggests a resistance to the metabolic effects of FGF19 and FGF21 in HIV-1-infected patients. Considering the beneficial effects of endocrine FGFs on metabolism, the observed reduction in FGF19 levels and decreased sensitivity to endocrine FGFs in adipose tissue may contribute to metabolic alterations in HIV-1-infected patients.
Assuntos
Fatores de Crescimento de Fibroblastos/sangue , Infecções por HIV/metabolismo , Tecido Adiposo/metabolismo , Adulto , Terapia Antirretroviral de Alta Atividade/efeitos adversos , Estudos de Casos e Controles , Feminino , Expressão Gênica , Infecções por HIV/sangue , Infecções por HIV/tratamento farmacológico , Infecções por HIV/genética , HIV-1 , Síndrome de Lipodistrofia Associada ao HIV/sangue , Síndrome de Lipodistrofia Associada ao HIV/etiologia , Síndrome de Lipodistrofia Associada ao HIV/metabolismo , Humanos , Proteínas Klotho , Masculino , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Pessoa de Meia-Idade , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/genética , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/metabolismoRESUMO
Nonalcoholic fatty liver disease (NAFLD) is a clinicopathologic syndrome that includes a range of disorders associated with fatty liver from steatosis to cirrhosis and hepatocellular carcinoma, defined by the presence of liver fat accumulation exceeding 5% of hepatocytes in the absence of other causes of liver disease such as alcohol consumption, viral hepatitis, or any other specific etiology. Half the patients with human immunodeficiency virus (HIV) who undergo additional testing for unexplained liver test abnormalities may suffer from NAFLD, which is the hepatic manifestation of the metabolic syndrome. In HIV-infected patients, NAFLD can result from the HIV itself, highly active antiretroviral therapy (HAART), and/or lipodystrophy. Evaluation of the liver impact of NAFLD remains mainly based on liver biopsy, but numerous noninvasive procedures are under evaluation. In HIV/hepatitis C virus (HCV-) coinfected patients, steatosis seems more frequent and severe by comparison with HCV-monoinfected patients, and is associated with significant liver fibrosis, which may contribute to the more rapid progression of liver disease. First-line treatment of NAFLD is mainly based on the adequate management of the metabolic syndrome, including lifestyle changes. Specific therapeutic approaches are under investigation.
Assuntos
Terapia Antirretroviral de Alta Atividade/efeitos adversos , Fígado Gorduroso/etiologia , Infecções por HIV/complicações , Síndrome de Lipodistrofia Associada ao HIV/etiologia , Hepatite C/complicações , Cirrose Hepática/etiologia , Síndrome Metabólica/complicações , Coinfecção , Fígado Gorduroso/fisiopatologia , Fígado Gorduroso/terapia , HIV , Síndrome de Lipodistrofia Associada ao HIV/prevenção & controle , Hepacivirus , Humanos , Cirrose Hepática/prevenção & controle , PrevalênciaRESUMO
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
The mechanisms behind certain co-morbid conditions associated with chronic HIV disease still remain elusive. HIV-associated peripheral neuropathy is one among those rarely studied manifestations in HIV-1 infection. Numerous underlying factors associated with peripheral neuropathy have been described in HIV disease. Herein, we hypothesized certain heretofore undescribed potential mechanisms that lead to HIV associated neuropathy. Being a multifactoral manifestation, HIV-associated neuropathy is presumed to have an association with physiological factors namely, adrenal inadequacy/steroid resistance and lipodystrophy-induced cushion-effect loss in peripheral nerves. Therefore, management of the adrenals with steroids at the time-point of high inflammatory burden thereby preventing lipodystrophy by selecting the optimum treatment regimen could markedly alleviate the severity of HIV-associated neuropathic manifestations.