Impact of Antiretroviral Therapy on Selected Metabolic Disorders – Pilot Study

Abstract

Background. Taking into consideration the aging of HIV infected individuals, changes in the metabolism aggravated by the antiretroviral therapy significantly impact their health. Mechanisms responsible for lipodystrophy, dyslipidemia and insulin resistance (IR) occurrence have not been completely understood. Only recently, the free fatty acids (FFAs) metabolic turnover has become considered to be the independent risk factor for cardiovascular complications. Material and Methods. We designed the follow-up study in which patients were recruited before the introduction of ARV therapy and then observed up to 1 year. The impact of ARV therapy on the development of metabolic complications, inflammation markers and changes in adipokines secretion was investigated. The fasting and postprandial responses of FFAs, triglycerides (TG), glucose, insulin and glucose-dependent insulinotropic peptide (GIP) were measured. Changes in body composition were followed by impedance and a CT scan of adipose tissue volume of the abdomen and thighs. Results. Significant impact of ARV therapy on metabolic disturbances was reported. Not only fasting, but also postprandial levels of FFAs and TG were found to increase during the follow up. Conclusions. The increased concentration of FFAs is suggested to be the triggering event in the development of hypertriglyceridemia and insulin resistance during ARV therapy. Changes in postprandial FFAs and TG during the follow up indicate the increasing risk of cardiovascular diseases. We conclude that modern ARV therapy during the period of 12 months does not induce changes in the fat distribution, although increased limb fat correlated with higher plasma leptin level, which may be the marker of increased risk of metabolic driven cardiovascular complications (Adv Clin Exp Med 2014, 23, 4, 539-549).

Increased chance of metabolic syndrome in women living with HIV/AIDS and lipodystrophic syndrome

“…Esta última, alteração lipídica mais frequente na infecção pelo HIV, especialmente em pacientes com SL, 39 podendo ser secundária à TARV 40 e decorrente da produção do clearence de LDL pelo fí-gado. 17,37 Os pacientes neste estudo apresentaram valores elevados de TG, sendo que 72,4% dos homens (21 dos 29) e 55,6% das mulheres (5 de 9) estavam com níveis acima do ponto de corte para SM (≥ 150 mg.dL -1 ).…”

Insulin Resistance and Glucose Dysregulation in HIV Treated Patients

“…Jasik et al proved that ARV therapy leads to an increase of fasting, as well as postprandial free fatty acids(FFAs). The study showed that even without significant lipodystrophy HIV infected individuals experienced increase lipolysis as well as can have adipocyte FFA trapping and these can be the triggered event in other metabolic complications as hypertriglyceridemia and IR [32]. Lipodystrophy may also result in B-cell dysfunction and is associated with impaired feedback of insulin on B-cells.…”

“…Insulin plays a major role in the induction of postprandial glucose uptake by stimulating insulin receptors on the cell surface resulting in glucose phosphorylation and translocation of glucose transporter 4(GLUT4) from the cell cytosol to the cell surface where glucose is taken into the cell [5].Interaction of this pathway in several points may result to IR [14], [24].Insulin normally suppresses hepatic glucose production and promotes hepatic glycogen and lipid synthesis.IR underlies many metabolic conditions, it is a core feature of T2DM and accompanied abdominal obesity, present in atherothrombotic cardiovascular disease(CVD) and underlies dyslipidemia characterized by hypertriglyceridemia and low HDL cholesterol.IR precedes the development of overt diabetes mellitus in many human and animal models [25]- [27] and is associated with elevated hepatic lipid contents in multiple disease models in non-HIV infected and HIV infected patients [28], [29]. The additional risk factors in HIV infected individuals are the proinflammatory effect of the HIV itself, the direct effect of HAART(especially PIs) and the indirect consequences of treatment through lipodystrophy [11], [30], [31],HCV-co-infection, low CD4 count and hepatic steatosis [32]- [34]. Guillen et al reported that age, diastolic blood pressure, weight, BMI, abdominal circumference and fasting blood glucose (FBG) was associated with IR among HIV patients as they were in general population [35].Early descriptions of IR in HIV infected HAART recipients were in the context of drug-induced lipodystrophy, a known insulin resistance state [14], [36], [37].…”

Estado da vitamina D e sua relação com doenças cardiovasculares em indivíduos com HIV/AIDS em tratamento com antirretrovirais: uma revisão sistemática.

“…As mesmas condições são encontradas em populações soronegativas, mas que apresentam baixas concentrações de vitamina D no organismo (STHEPHEN CB et al, 2006). A hipovitaminose D tem atingido proporções epidêmicas em todo o mundo, envolvendo também indivíduos infectados pelo vírus da imunodeficiência humana (HIV) e os que apresentam a síndrome da imunodeficiência adquirida (AIDS) (BOCIAGA-JASIK et al, 2014).…”

“…artigos incluídos resultaram numa população de 2.581 indivíduos, sendo 2.497 indivíduos HIV-positivo, onde 15 desses foram locados em grupo controle e 84 indivíduos HIV-negativo e saudáveis participantes de outros grupos controles.Desta forma com uma população em sua maioria composta por homens, com maior predominância de negros, e com uma faixa etária de adultos-jovens este presente estudo enquadra-se dentro dos grupos de risco entre indivíduos HIVpositivo para deficiência de vitamina D e doenças cardiovasculares(ROSS et al, 2012). Sabe-se que após 6 meses de terapia antirretroviral os efeitos colaterais que agravam o sistema circulatório podem aparecer(BOCIAGA-JASIK et al, 2014), que os negros apresentam maior incidência de deficiência de vitamina D, devido a pigmentação da pele(LAI, S. et al, 2013) e que o sexo masculino de acordo com o aumento da faixa etária está mais predisposto as doenças cardiovasculares. (LAI, H. Um estudo(LONGENECKER et al, 2012) relatou os meses de sua coleta, portanto, encontram-se suas análises no inverno, primavera e verão.…”