Addition of Maraviroc Versus Placebo to Standard Antiretroviral Therapy for Initial Treatment of Advanced HIV Infection: A Randomized Trial.

Background: Patients diagnosed with advanced HIV infection have a poor prognosis despite initiation of combined antiretroviral therapy (c-ART). Objective: To assess the benefit of adding maraviroc, an antiretroviral drug with immunologic effects, to standard c-ART for patients with advanced disease at HIV diagnosis. Design: Randomized controlled trial. (ClinicalTrials.gov: NCT01348308). Setting: Clinical sites in France (n = 25), Italy (n = 5), and Spain (n = 20). Participants: 416 HIV-positive, antiretroviral-naive adults with CD4 counts less than 0.200 × 109 cells/L and/or a previous AIDS-defining event (ADE). Intervention: C-ART plus placebo or maraviroc (300 mg twice daily with dose modification) for 72 weeks. Measurements: The primary end point was first occurrence of severe morbidity (new ADE, selected serious infections, serious non-ADE, immune reconstitution inflammatory syndrome, or death). Prespecified secondary outcomes included primary outcome components, biological and pharmacokinetic measures, and adverse events graded 2 or higher. Results: 409 randomly assigned participants (207 in the placebo group and 202 in the maraviroc group) who received more than 1 dose were included in the analysis. During 72 weeks of follow-up, incidence of severe morbidity was 11.1 per 100 person-years in the maraviroc group and 11.2 per 100 person-years in the placebo group (hazard ratio, 0.97 [95% CI, 0.57 to 1.67]). Incidence of adverse events graded 2 or higher was 36.1 versus 41.5 per 100 person-years (incidence rate ratio, 0.87 [CI, 0.65 to 1.15]). Limitations: Sixty-four participants discontinued therapy during follow-up. The study was not designed to evaluate time-dependent outcomes or effect modification. Conclusion: Addition of maraviroc to standard c-ART does not improve clinical outcomes of patients initiating therapy for advanced HIV infection. Primary Funding Source: INSERM-ANRS (French National Agency for Research on AIDS).

Insulin resistance and the metabolic syndrome are related to the severity of steatosis in the pediatric population with obesity.

BACKGROUND: To determine the factors associated with an increased risk for severe steatosis (SS) and establish the Homeostatic Model Assessment-Insulin Resistance (HOMA-IR) as a screening tool. METHODS: A cross-sectional study was performed in obese children to assess the relationship between the metabolic syndrome (MetS) and glucose metabolism alterations (GMA) and the risk for severe steatosis. RESULTS: A total of 94 children (51 males) aged from six to 14 years were included. Thirteen children (14.8%) had severe steatosis (SS). The anthropometric variables associated with SS included body mass index (BMI) (SS 34.1 vs non-SS 29.7, p = 0.005), waist circumference (cm) (100 vs 92.5, p = 0.015) and hip circumference (cm) (108 vs 100, p = 0.018). The blood parameters included alanine aminotransferase (ALT) (UI/dl) (27 vs 21, p = 0.002), gamma-glutamil transpeptidase (GGT) (UI/dl) (16 vs 15, p = 0.017), fasting glycemia (mg/dl) (96 vs 88, p = 0.006), fasting insulin (UI/dl) (25 vs 15.3, p < 0.001) and HOMA-IR score (7.1 vs 3.7, p < 0.001). Eighteen children with MetS were found to be at an increased risk for severe steatosis (odds ratio [OR] 11.36, p < 0.001). After receiver operating characteristic (ROC) curve analysis, the best area under the curve (AUC) was obtained for HOMA-R of 0.862. The HOMA-R 4.9 cut-off value had a 100% sensitivity (CI 95%: 96.2-100) and 67.9% specificity (CI 95%: 57.1-78.7) for severe steatosis. CONCLUSIONS: The presence of MetS and glucose metabolism alterations are risk factors for severe steatosis. The 4.9 cut-off value for HOMA-IR may be a risk factor for severe steatosis in obese children.

Hepatic steatosis and severity-related factors in obese children.

BACKGROUND AND AIM: Obesity is an important health-care problem in developed countries. It is considered a multisystemic disease, but it may also affect the liver, thus provoking non-alcoholic fatty liver disease. This disease has been less extensively studied among children than among adults. We propose to analyze the prevalence of hepatic steatosis among a pediatric population within an area in southern Europe besides the variables associated with its development and severity. METHODS: Cross-sectional study carried out on a population of children aged 6-14 years inclusive, using abdominal ultrasound as a method to determine the presence and severity of hepatic steatosis; in addition, anthropometric and blood-tested parameters were examined to determine which of these were associated with steatosis. RESULTS: One hundred forty-four children were analyzed, 84 male (58.3%). Steatosis was detected in 50 children (34.7%; 95% confidence interval [CI]: 26.0-42.0%). In six of these cases (12%), elevated aminotransferase levels were recorded. Factors found to be associated with steatosis were body mass index ≥ 99th percentile (odds ratio [OR] 3.58, 95% CI 1.16-15.6) and the level of alanine aminotransferase (ALT) (OR 1.08, 95% CI 1.03-1.13), while its severity was associated with ALT (OR 1.17, 95% CI 1.09-1.28). A level of ALT < 23.5 UI/dL predicted lack of severe steatosis with an area under receiver operating characteristic curve of 0.805 (95% CI 0.683-0.927). CONCLUSIONS: Non-alcoholic fatty liver disease is common in the obese pediatric population in our geographical area. High levels of ALT are associated with severe steatosis, although having ALT above the normal range is not common. Also, the lack of severity of steatosis can be predicted in a subgroup of children with obesity.

[Incidence and clinico-epidemiological aspects of ulcerative colitis in the area of the Hospital Costa del Sol]. / Incidencia y aspectos clinicoepidemiológicos de la colitis ulcerosa en el área de influencia del Hospital Costa del Sol.

INTRODUCTION: The incidence of inflammatory bowel disease, and of ulcerative colitis in particular, varies widely according to geographical area and has been reported to have increased in the last few years, although some of the differences observed may be due to the methodology employed. OBJECTIVES: To determine the incidence of ulcerative colitis in our area and to compare it with that described in other areas of Spain and Europe, as well as to describe certain clinico-epidemiological aspects of this disease. MATERIAL AND METHODS: A descriptive, prospective, population-based study was performed from 2000-2001 in patients diagnosed with ulcerative colitis in the catchment area of the Hospital Costa del Sol, with a population of 210,384 inhabitants. The crude incidence rate was adjusted by the direct method, using the European standard population (EU-25, 2000) as the reference population; 95% confidence intervals were calculated. RESULTS: Forty-three patients (23 men [53.5%] and 20 women [46.5%], with a mean age of 35.23 years [SD=15.42]) were included. Thirty-three percent were residents of the Hospital Costa del Sol's catchment area and were included in the calculation of incidence. The crude incidence was 7.84 and the incidence adjusted by age and sex to the European population was 7.26 per 100,000 inhabitants/year. CONCLUSIONS: The incidence of ulcerative colitis in the area of the Hospital Costa del Sol is higher than that found in other studies performed in the autonomous community of Andalusia as well as that observed in some studies performed in the north of the Peninsula.

[Distinct clinical presentations of a single medical entity: eosinophilic enteritis]. / Diferentes formas de presentación de una misma entidad clínica: gastroenteritis eosinofílica.

Eosinophilic enteritis is a rare disease characterized by eosinophilic infiltration of different wall layers of the gastrointestinal tract, from the esophagus to the rectum, by eosinophilic cells. The most frequently affected structures are the stomach and small intestine. The pathogenesis of eosinophilic enteritis is not well understood and is often related to a personal or familial history of atopy. Clinical symptoms depend on the affected layers. Thus malabsorptive syndrome, intestinal strictures or ascites depend on a mucosal, muscular or serosa layer infiltration, respectively. We present three cases of eosinophilic gastroenteritis with distinct clinical presentations.

Lipid changes in patients initiating efavirenz- and indinavir-based antiretroviral regimens.

PURPOSE: To evaluate nonfasting lipid levels in a large cohort of patients on three HAART regimens: efavirenz + zidovudine + lamivudine (EFV+ZDV+3TC), efavirenz + indinavir (EFV+IDV), and indinavir + zidovudine + lamivudine (IDV+ZDV+3TC). METHOD: Nonfasting lipid levels were analyzed from a large randomized multicenter treatment trial for HIV-infected patients initiating HAART. Treatment evaluations were carried out at prescribed intervals, and data were recorded and analyzed. Assessment was limited to high-density lipoprotein (HDL) and total cholesterol. RESULTS: The results demonstrate an increase in the total cholesterol, ranging from 23 to 57 mg/dL, in the three combinations of HAART therapy. The increase was most significant in the EFV+IDV arm where the effects appear to be additive. HDL cholesterol also increased in all three arms, but the greatest increase was in the two groups containing EFV. In all three arms, the HDL cholesterol increased significantly in women while increases in men were seen only in the EFV-containing arms. Men taking either IDV-containing regimen had a greater increase in total cholesterol, and therefore the total/HDL cholesterol ratio rose significantly. CONCLUSION: EFV and IDV independently elevate lipid levels. Alterations in the lipid levels may lead to increased cardiovascular risk in men, possibly mitigated by elevations in HDL cholesterol. In addition, changes in HDL cholesterol were significantly different between men and women.

Serum levels of beta2-microglobulin, neopterin, TNF-alpha and soluble receptors of TNF-alpha and interleukin-2 in intravenous drug abusers according to HIV-1 status and stage of the HIV-1 infection.

OBJECTIVE: To compare the serum levels of beta2-microglobulin (beta2M), neopterin (NP), TNF-alpha and soluble receptors of TNF-alpha (sTNF-R55 and sTNF-R75) and interleukin-2 (sIL-2R) in a population of intravenous drug abusers according to whether or not they had HIV-1 infection and to the stage of the HIV-1 infection. METHODS: A cross-sectional study was performed at four drug detoxification centers in Barcelona, and the HIV outpatient clinic at Hospital Clínic in Barcelona. Three cohorts of intravenous drug abusers (IVDAs)-105 HIV-1-uninfected patients (cohort A), 174 with asymptomatic HIV-1 infection (cohort B) and 39 with AIDS (cohort C)-were enrolled. On the first visit, the following laboratory tests were performed: hemogram and platelet count, hepatitis B surface antigen (HBsAg), anti-hepatitis C antibodies, B2M, NP, sIL-2R, TNF-alpha, and TNF receptors (sTNF-R55 and sTNF-R75). RESULTS: The three cohorts were homogeneous according to sex, type of drug, average number of intravenous doses of drug in 1 day, and hepatitis B infection. Patients with AIDS were older than those of cohort A and B (p<0.0001). HIV-negative IVDAs were co-infected with hepatitis C virus less frequently than were HIV-positive IVDAs (80% versus 91%, p<0.03). Among HIV-1-negative IVDAs (cohort A), almost all (from 86% to 95%, depending on the marker) individual values were within the normal boundaries of our laboratory. With a single exception (level of sTNF-R55 in cohort B compared with cohort A, p=0.15), levels of all markers were significantly higher in asymptomatic HIV-1-infected (cohort B) when compared with uninfected patients (cohort A), and in AIDS patients (cohort C) when compared with both cohorts A and B. There was a significant positive correlation between levels of ss2M and NP (r=0.56; p<0.01), ss2M and TNF (r=0.65, p<0.01) and NP and TNF (r=0.76, p<0.01). There was no correlation between levels of sIL-2R and levels of ss2M, NP or TNF and its receptors. CONCLUSIONS: Intravenous drug abuse does not modify serum levels of ss2M, NP, sIL-2R, TNF-alpha, and TNF receptors (sTNF-R55 and sTNF-R75). Levels of these markers increase significantly when an HIV-1 infection occurs and when there is progression to AIDS.