Publications (29) View all
-
Article: Leptin and adiponectin, but not IL18, are related with insulin resistance in treated HIV-1-infected patients with lipodystrophy.
[show abstract] [hide abstract]
ABSTRACT: Leptin, adiponectin and IL18 are adipokines related with obesity, insulin resistance and dyslipidemia in the general population. Treated HIV-1-infected patients with lipodystrophy may develop insulin resistance and proatherogenic dyslipidemia. We assessed the relationship between plasma adipokine levels, adipokine genetics, lipodystrophy and metabolic disturbances. Plasma leptin, adiponectin and IL18 levels were assessed in 446 individuals: 282 HIV-1-infected patients treated with antiretroviral drugs (132 with lipodystrophy and 150 without) and 164 uninfected controls (UC). The LEP2410A>G, LEPRQ223R, ADIPQ276G>T, ADIPOR2-Intron5A>G and IL18-607C>A polymorphisms were validated by sequencing. Leptin levels were higher in UC than in HIV-1-infected, either with or without lipodystrophy (p<0.001 for both comparisons) and were lower in patients with lipodystrophy compared with those without lipodystrophy (p=0.006). In patients with lipodystrophy, leptin had a positive correlation with insulin and with HOMA-IR. Adiponectin levels were non-significantly different in UC and HIV-1-infected patients. Patients with lipodystrophy had lower adiponectin levels than non-lipodystrophy subjects (p<0.001). In patients with lipodystrophy, adiponectin was negatively correlated with insulin, HOMA-IR and triglycerides. Plasma IL18 levels were higher in HIV-1-infected patients compared with UC (p<0.001), and no differences were found according to the presence of lipodystrophy. In patients with lipodystrophy there was a negative correlation between IL18 levels and LDLc. Genetic analyses indicated no significant associations with lipodystrophy nor with insulin resistance or with lipid abnormalities. In conclusion, HIV-1-infected patients have reduced plasma leptin levels. This reduction is magnified in patients with lipodystrophy whose adiponectin levels were lower than that of non-lipodystrophy subjects. Plasma IL18 levels are increased in infected patients irrespective of the presence of lipodystrophy. The polymorphisms assessed are not associated with lipodystrophy or metabolic disturbances in treated HIV-1-infected patients.Cytokine 02/2012; 58(2):253-60. · 3.02 Impact Factor -
Article: Zinc alpha-2 glycoprotein is implicated in dyslipidaemia in HIV-1-infected patients treated with antiretroviral drugs.
[show abstract] [hide abstract]
ABSTRACT: Treated HIV-1-infected patients with lipodystrophy often develop insulin resistance and proatherogenic dyslipidaemia. Zinc alpha-2 glycoprotein (ZAG) is a recently characterized adipokine which has been shown to be involved in the development of obesity and metabolic syndrome in uninfected subjects. We assessed the relationship between circulating ZAG levels and metabolic derangements in HIV-1-infected patients receiving antiretroviral drugs. Plasma ZAG levels were assessed in 222 individuals: 166 HIV-1-infected patients treated with antiretroviral drugs (77 with lipodystrophy and 89 without lipodystrophy) and 56 uninfected controls. Plasma ZAG levels were assessed by enzyme-linked immunosorbent assay (ELISA) and were correlated with fat distribution abnormalities and metabolic parameters. HIV-1-infected patients had lower plasma ZAG levels compared with uninfected controls (P < 0.001). No differences were found in ZAG plasma levels according to the presence of lipodystrophy, components of the metabolic syndrome or type of antiretroviral treatment regimen. Circulating ZAG levels were strongly determined by high-density lipoprotein cholesterol (HDLc) in men (B = 0.644; P < 0.001) and showed a positive correlation with total cholesterol (r = 0.312; P < 0.001) and HDLc (r = 0.216; P = 0.005). HIV-1-infected patients have lower plasma ZAG levels than uninfected controls. In infected patients, plasma ZAG levels are in close relationship with total cholesterol and HDLc.HIV Medicine 01/2012; 13(5):297-303. · 3.01 Impact Factor -
Article: A study of fatty acid binding protein 4 in HIV-1 infection and in combination antiretroviral therapy-related metabolic disturbances and lipodystrophy.
[show abstract] [hide abstract]
ABSTRACT: The aim of the study was to determine circulating levels of fatty acid binding protein 4 (FABP-4) in a cohort of HIV-1-infected patients treated with combination antiretroviral therapy (cART) and to investigate the relationships between FABP-4 levels and insulin resistance, dyslipidaemia, lipodystrophy and levels of proinflammatory adipocytokines in these patients. A total of 282 HIV-1-infected patients treated with stable cART for at least 1 year (132 with lipodystrophy and 150 without) and 185 uninfected controls (UCs) were included in the study. Anthropometric parameters were determined. Plasma levels of FABP-4, soluble tumour necrosis factor receptors 1 and 2 (sTNF-R1 and sTNF-R2), interleukin-18 (IL-18), IL-6, adiponectin and leptin were also analysed. Insulin resistance was determined using the homeostasis model assessment of insulin resistance (HOMA-IR). Subcutaneous adipose tissue mRNA expression of proinflammatory cytokines was assessed in 38 patients (25 with lipodystrophy and 13 without) by real-time polymerase chain reaction (PCR). The plasma FABP-4 concentration was significantly higher in patients with lipodystrophy than in those without (P=0.012). FABP-4 concentration was positively correlated with body mass index (BMI), HOMA-IR, and the concentrations of insulin, total cholesterol, triglycerides, sTNF-R1, leptin and IL-18, but showed a negative correlation with high-density lipoprotein (HDL) cholesterol and adiponectin concentrations. After adjusting for age, sex and BMI, the odds ratio (OR) for risk of lipodystrophy was found to be significantly increased for those with the highest levels of FABP-4 [OR 0.838, 95% confidence interval (CI) 0.435-1.616 for medium FABP-4 vs. OR 2.281, 95% CI 1.163-4.475 for high FABP-4]. In a stepwise regression model, FABP-4 was independently associated with HOMA-IR after controlling for clinical and inflammatory parameters (P=0.004). Moreover, a positive relationship was observed in patients with lipodystrophy between subcutaneous adipose tissue CD68 expression and FABP-4 plasma levels (r=0.525; P=0.031). cART-treated HIV-1-infected patients with lipodystrophy have a systemic overproduction of FABP-4, which is closely linked to insulin resistance and inflammatory markers in subcutaneous adipose tissue.HIV Medicine 01/2011; 12(7):428-37. · 3.01 Impact Factor -
Article: Similar antiviral efficacy and tolerability between efavirenz and lopinavir/ritonavir, administered with abacavir/lamivudine (Kivexa), in antiretroviral-naïve patients: a 48-week, multicentre, randomized study (Lake Study).
[show abstract] [hide abstract]
ABSTRACT: Although efavirenz and lopinavir/ritonavir(r) are both recommended antiretroviral agents in antiretroviral-naïve HIV-infected patients, there are few randomized comparisons of their efficacy and tolerability. A multicenter and randomized study was performed including 126 antiretroviral-naïve patients, randomly assigned to efavirenz+Kivexa (n=63) or lopinavir/r+Kivexa (n=63). Efficacy endpoints were the percentage of patients with HIV-RNA < or =50 copies/mL at week 48 and CD4 recovery. Safety was assessed by comparing toxicity and discontinuations. Statistical analyses were performed on an intention-to-treat (ITT) basis (Missing=Failure). At week 48, 56.7% of patients in the efavirenz and 63.2% in the lopinavir/r groups showed HIV-1 RNA <50 copies/mL (P=0.770) (intention-to-treat analysis; Missing=Failure). Only 1 (1.53%) patient from each group experienced virological failure. CD4 values increased in both groups (298 cells in the efavirenz group, P=0.001; 249 cells in the lopinavir/r group, P=0.002; P=0.126 between groups). HDL-cholesterol only increased in the efavirenz group (from 39+/-12 mg/dL to 49+/-11; P=0.001). Discontinuations were more frequent in the lopinavir/r group (36.5% versus 28.5%; P=0.193), but more patients with efavirenz interrupted due to toxicity (11.1% versus 6.3%); most of them were attributed to hypersensitivity reaction. Similar virological efficacy was observed for efavirenz and lopinavir/r, when administered with Kivexa in antiretroviral-naïve patients, while immunological improvement was slightly superior for efavirenz. The higher rate of discontinuation due to toxicity in the efavirenz group was related to a higher incidence of hypersensitivity reaction. Nowadays, the use of the new formulation of lopinavir/r and the HLA-B*5701 genotype test before starting abacavir should improve the safety profiles of these regimens.Antiviral research 11/2009; 85(2):403-8. · 3.61 Impact Factor -
Article: Pharmacogenetics of the lipodystrophy syndrome associated with HIV infection and combination antiretroviral therapy.
[show abstract] [hide abstract]
ABSTRACT: INTRODUCTION: Antiretroviral drugs have been associated with several toxicities that limit their success. Of the chronic toxicities, the lipodystrophy syndrome is of special concern due to the metabolic alterations that can accompany it. Why some patients treated with a particular antiretroviral regimen develop lipodystrophy, while others do not, is a medical mystery, but it has been suggested that individuals may (or may not) have a genetically conditioned predisposition. Pharmacogenetics is the science that studies how the genetic composition of individuals can give rise to interindividual variations in response to drugs and drug toxicity. AREAS COVERED: This article reviews the published investigations on the association between host genetic determinants in treated HIV-infected patients and the presence of lipodystrophy. Studies were identified through a PubMed database search. Case-control and longitudinal studies into pharmacogenetic association were selected. Areas covered include the data on the genetic variants of mitochondrial parameters, cytokines, adipokines, proteins involved in adipocyte biology and proteins involved in stavudine metabolism. EXPERT OPINION: Most studies provide inconsistent data due to partial genetic evaluation, different assessment of lipodystrophy and low number of patients evaluated. The pharmacogenetics of lipodystrophy in HIV-infected patients treated with antiretroviral drugs still belongs in the research laboratory.Expert Opinion on Drug Metabolism & Toxicology 11/2011; 7(11):1365-82. · 3.12 Impact Factor
