RESUMEN
OBJECTIVES: Because female sex protects against dyslipidaemia and atherosclerosis in normal subjects, we aimed to reveal potential sex differences in metabolic side-effects of a newly initiated highly active antiretroviral therapy (HAART) regimen, and to relate these changes to endothelial cell activation as measured by levels of circulating E-selectin (cE-selectin). DESIGN: Prospective longitudinal cohort study. SETTING: Tertiary care centre at a University Hospital. METHODS: HIV-seropositive male (n = 27) and female patients (n = 13) with a plasma viral load of > or = 10 000 copies/ml and 35 healthy controls were enrolled in the study. All participants were weight stable, free of acute opportunistic infections, and had not taken any protease inhibitors before. Serum levels of lipids, insulin, leptin, and cE-selectin were measured before initiation of HAART, and at 3 and 6 months thereafter. RESULTS: HAART increased serum levels of triglycerides, leptin, and low-density lipoprotein (LDL) cholesterol; these effects were more distinct in women. Fasting insulin levels and the LDL : high density lipoprotein (HDL) ratio increased only in female HIV-infected patients (P < 0.02 versus men). In contrast, endothelial activation, as measured by cE-selectin, decreased more in men (P < 0.02) than in women. As a consequence, women had higher triglycerides and leptin levels after therapy than did men, and the LDL : HDL ratio and cE-selectin levels, which were initially higher in men, were no longer different between the sexes. CONCLUSIONS: Metabolic adverse effects during HAART are more pronounced in women than in men. Hence, female HIV-infected patients seem to loose part of their natural protection from atherosclerosis during antiretroviral therapy.
Asunto(s)
Terapia Antirretroviral Altamente Activa/efectos adversos , Infecciones por VIH/tratamiento farmacológico , Hiperlipidemias/inducido químicamente , Adulto , Composición Corporal , Peso Corporal , Recuento de Linfocito CD4 , Selectina E/sangre , Endotelio Vascular/metabolismo , Femenino , Humanos , Insulina/sangre , Leptina/sangre , Lípidos/sangre , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Factores Sexuales , Carga ViralAsunto(s)
Síndrome de Inmunodeficiencia Adquirida/tratamiento farmacológico , Síndrome de Inmunodeficiencia Adquirida/fisiopatología , Fármacos Anti-VIH/uso terapéutico , Composición Corporal/efectos de los fármacos , Metabolismo Energético/efectos de los fármacos , Inhibidores de la Proteasa del VIH/uso terapéutico , Seropositividad para VIH/tratamiento farmacológico , Seropositividad para VIH/fisiopatología , Nelfinavir/uso terapéutico , Peso Corporal , Dieta , Quimioterapia Combinada , Ingestión de Energía , Estudios de Seguimiento , Humanos , Aumento de Peso/efectos de los fármacosRESUMEN
OBJECTIVES: (i) To investigate whether protease inhibitor (PI) (nelfinavir)-containing highly active antiretroviral therapy (HAART) affects body composition differently in HIV-infected and AIDS patients without wasting syndrome. (ii) To delineate the changes in resting energy expenditure (REE) under PI therapy, and to determine whether sustained reductions in HIV RNA would decrease REE. DESIGN: Prospective longitudinal cohort study with individually matched healthy controls. SETTING: Tertiary care centre at a University Hospital. METHODS: HIV-seropositive (n = 20) and AIDS patients (n = 17) with a plasma viral load of at least 10000 copies/ml and 37 healthy volunteers were enrolled. All participants were weight stable, free of acute opportunistic infections, and naive to PI therapy. Patients underwent testing of bioelectrical impedance analysis (BIA), indirect calorimetry and food intake, shortly before the initiation of HAART and 24 weeks thereafter. RESULTS: Both patient groups gained weight, body mass index (BMI), and fat-free mass (FFM) (P < 0.05 versus baseline), whereas only AIDS patients gained fat mass. Increases were more pronounced in the AIDS group. REE was elevated compared with corresponding controls at baseline, and decreased similarly in HIV and in AIDS patients during PI therapy (P < 0.05). The reduction in the viral burden preceded the decrease in REE by several weeks. CONCLUSION: Body composition and metabolic parameters improved during PI therapy in HIV-infected and AIDS patients without wasting. Although an early reduction in viral load as a result of HAART does not seem to influence REE directly, sustained viral load suppression may promote a decrease in energy expenditure.