Association between the IL28B genotype and hepatitis C viral kinetics in the early days of treatment with pegylated interferon plus ribavirin in HIV/HCV co-infected patients with genotype 1 or 4.

OBJECTIVES: To evaluate the effect of the interleukin 28B (IL-28B) genotype on hepatitis C virus (HCV) viral kinetics in the first 4 weeks from start of treatment with pegylated interferon plus ribavirin (PEG-IFN/RBV) in HIV/HCV co-infected patients. METHODS: HIV/HCV co-infected patients naive to PEG-IFN/RBV treatment were enrolled in a prospective study. HCV RNA plasma viral loads were measured at baseline and at weeks 1, 2 and 4 after commencement of treatment. Patients were grouped by HCV genotype (genotype 1/4 versus 3) and by IL-28B genotype (CC versus non-CC). Differences in viral load reduction were evaluated by IL-28B genotype between baseline, week 1, week 2 and week 4. RESULTS: One hundred and nineteen HIV/HCV patients were included in the study. HCV patients with genotype 1/4 and bearing the IL-28 CC genotype showed the greatest reductions in HCV RNA plasma levels between baseline and weeks 1 (B-1), 2 (B-2) and 4 (B-4) than did those with non-CC genotypes (B-1: 1.06 ± 0.89 versus 0.48 ± 0.48 log IU/mL, P = 0.009; B-2: 1.36 ± 0.72 versus 0.77 ± 0.66 log IU/mL, P = 0.01; and B-4: 1.91 ± 0.64 versus 1.38 ± 0.96 log IU/mL, P = 0.03). However, differences between weeks 1 and 2 (W1-2) and between weeks 2 and 4 (W2-4) were not associated with the IL-28B genotype (W1-2: CC 0.48 ± 0.42 versus non-CC 0.38 ± 0.38 log IU/mL, P = 0.62; W2-4: CC 0.32 ± 0.23 versus non-CC 0.39 ± 0.31 log IU/mL, P = 0.67). No differences in decline of HCV RNA viral load were found in HCV genotype 3 patients. CONCLUSIONS: The IL-28B genotype impacts on viral kinetics during the first week of treatment with PEG-IFN/RBV in patients with HCV genotype 1/4.

[Use of rifampicin plus pyrazinamide for antituberculosis prophylaxis does not increase the risk of severe hepatotoxicity in HIV patients: meta-analysis of randomized controlled clinical trials]. / Usar rifampicina más pirazinamida en profilaxis antituberculosa no incrementa el riesgo de hepatotoxicidad grave en pacientes infectados por virus de la inmunodeficiencia humana: metaanálisis de ensayos clínicos aleatorizados y controlados.

OBJECTIVE: To compare the incidence of severe hepatitis in HIV-infected patients receiving rifampicin plus pyrazinamide (RZ) for antituberculosis prophylaxis with that of patients receiving a conventional isoniazid-based regime for 6 to 12 months (6-12H). METHODS: Meta-analysis of randomized controlled trials, in which RZ was compared with 6-12H, the standard regimen for latent tuberculosis infection in HIV-infected patients. A systematic search of studies published between 1986 and 2007 was carried out, and 5 randomized clinical trials conducted in Spain (2), the USA (1), Haiti (1), and Zambia (1) were identified. The absence or presence of severe hepatoxicity, which was defined as toxicity causing the death of the patient or requiring treatment withdrawal, was assessed as a binary response, and the outcome measure was the difference in the risk of hepatotoxicity between patients receiving RZ and those receiving 6-12H (controls). RESULTS: Among the 5 trials retrieved, 1 was excluded from the final analysis because of incomplete data on the development of hepatotoxicity. A final total of 2657 patients were included (1324 patients receiving RZ and 1333 receiving 6-12H). The development of severe hepatotoxicity was lower in the RZ group than in the 6-12H group (1.208% vs. 2.851%; P=0.0042, 95% CI: -0.028 to -0.005). The meta-analysis showed no statistical evidence of heterogeneity between the studies or publication bias. The difference in the risk of severe hepatotoxicity favored the RZ regimen in both the fixed effects model (-0.0119, 95% CI: -0.0206 to -0.0033) and random effects model (-0.0147, 95% CI: -0.0289 to -0.0006). CONCLUSIONS: The meta-analysis did not demonstrate an increased risk of severe hepatoxicity in HIV-infected patients receiving tuberculosis prophylaxis with the rifampicin/pyrazinamide combination compared to the conventional 6- or 12-month isoniazid-based regimen.

Systematic review about 10 interventions in dermatitis. A document from the Latin American Society of Allergy, Asthma, and Immunology.

The Latin American Society of Allergy, Asthma, and Immunology (SLAAI) conducted a systematic search in the Medline and LILACS' database in order to get articles linked to 10 current questions about dermatitis. The assessment of the quality of the evidence and the strength of the recommendations was made through the GRADE system. The completeness and transparency of the recommendations for this clinical guide were assessed with the AGREE Reports Verification Checklist. The final document was shared with physicians, allergists, dermatologists, and pediatricians, and with patients and academic institutions such as universities and medical scientific societies for external assessment. According to the review, clinical scales should be used to measure the severity of the dermatitis, and some interventions such as the use of probiotics may benefit the patient; nevertheless, more studies are required before this management option can be used in the everyday practice. Other interventions such as dietary restrictions and the use of antihistamines seem to be well-founded only in particular cases and they should not be a general recommendation for all patients. This practical guide presents recommendations for the treatment of atopic dermatitis; these recommendations can be helpful for medical staff, patients, and health systems.

La Sociedad Latinoamericana de Asma, Alergia e Inmunología realizó una búsqueda sistemática en la base de datos de Medline y LILACS para obtener artículos relacionados con 10 preguntas actuales sobre dermatitis. La evaluación de la calidad de la evidencia y la fuerza de las recomendaciones se realizaron a través del sistema GRADE. La integridad y la transparencia de las recomendaciones se evaluaron con la lista de verificación de informes AGREE. El documento final se compartió con médicos, alergólogos, dermatólogos y pediatras, pacientes e instituciones académicas, como universidades y sociedades médicas científicas, para su evaluación externa. Conforme a la revisión, se debe usar escalas clínicas para evaluar la gravedad de la dermatitis; algunas intervenciones como el uso de probióticos pueden beneficiar al paciente, sin embargo, se requieren más estudios antes de utilizarlas en la práctica diaria. La restricción de la dieta y el uso de antihistamínicos parecen tener fundamento solo en casos particulares y no deben indicarse a todos los pacientes. Esta guía práctica presenta recomendaciones para el tratamiento de la dermatitis atópica que pueden ser útiles para el personal médico, los pacientes y los sistemas de salud.

[Malnutrition as a prognostic factor in elderly patients with hip fractures]. / Desnutrición como factor pronóstico en ancianos con fractura de cadera.

BACKGROUND AND OBJECTIVE: Hip fracture occurs frequently in elderly patients, with devastating effects on the quality of life due to the high financial burden and the high mortality rate in patients with this condition. Malnutrition is prevalent in the elderly and it can negatively influence patients' recovery from hip fracture. Our proposal was to assess the relationship between malnutrition and the recovery of patients with hip fracture. PATIENTS AND METHOD: A total of 110 patients with hip fractures who were admitted to the orthopedic unit at the Reina Sofía Hospital were reassessed one year after discharge. A prospective cohort design and logistic regression analysis was used. RESULTS: Mean age was 81.4, and 80% of patients were women. After one year 19.7% of patients had died. A multivariate analysis showed a significant relationship between a poor functional recovery and age (odds ratio [OR] = 1.19), caloric malnutrition (OR = 290), protein malnutrition (OR = 125); and there was a significant relationship between being confined to bed and a worse situation before fracture (OR = 10.02); caloric malnutrition (OR = 9.57) and protein malnutrition (OR = 15.23). CONCLUSIONS: Caloric and protein malnutrition were associated with a worse functional recovery in elderly patients with hip fracture.

[Variability in coronary risk assessment in HIV-infected patients]. / Variabilidad en la valoración del riesgo coronario en pacientes infectados por el virus de la inmunodeficiencia humana.

BACKGROUND AND OBJECTIVE: Antiretroviral treatment of human immunodeficiency virus (HIV)-infected patients seems to increase the coronary risk (CR) in these patients. Adequate assessment of CR has significant implications for the management of these patients. Our objective was to compare 2 systems for assessing 10-year CR in HIV-infected patients. PATIENTS AND METHOD: CR was calculated in a prospective cohort of 205 HIV-infected patients using Framingham tables and REGICOR adapted tables. Prevalence of cardiovascular risk factors in these patients was evaluated. RESULTS: Mean age (standard deviation) was 41.4 (8.2) years. Most patients were taking antiretrovirals and had a good immunological status. Current smoking was reported by 77.1% of patients, while a history of dyslipidemia, hypertension, or diabetes was found in 29.3%, 7.3%, and 4.9% of patients, respectively. Lipodystrophy was seen in 41% of patients, abdominal obesity in 21.5%, and a sedentary lifestyle in 50.7% Mean values obtained were 6.55 (6.36) in the Framingham scale and 2.85 (2.31) in the REGICOR scale. A 10-year CR greater than 10% was found in 26 patients (12.9%) with the Framingham tables and in 4 patients (2.0%) with the REGICOR tables. The difference between both methods was significant (p < 0.001). CONCLUSIONS: Application of the Framingham tables to our cohort may overestimate the CR. Studies aimed at identifying the most adequate method for measuring CR in HIV-infected patients are required. Until such data are available, estimation of CR in these patients should be taken with caution.

Low incidence of severe liver events in HIV patients with and without hepatitis C or B coinfection receiving lopinavir/ritonavir.

OBJECTIVES: To analyze the incidence of severe liver events in HIV patients treated with lopinavir/ritonavir and the role of coinfection in the development of this toxicity. METHOD: This was a retrospective, multicenter, cohort study of all HIV-positive patients who started a regimen of HAART that included lopinavir/ritonavir (LPV/r). The main outcome variable was the emergence of a severe liver event, defined as decompensation of pre-existing chronic liver disease and grade 3-4 hypertransaminasemia (HT), that is, plasma AST or ALT values >5 times above the upper limit of normality, if baseline levels were normal, or >3.5 times the baseline values when they were abnormal. RESULTS: 388 HIV-infected patients were included, with a median follow-up of 25.6 months. Coinfection with HCV was present in 61% of the patients and with HBV in 6.7%. There were 6 cases of severe liver events, all involving patients who were coinfected with HCV and all within the first 6 months. This represents 0.72 events per 100 patient-years (95% confidence interval [CI] 0.36-2.98) and 1.21 events per 100 patient-years (95% CI 0.60-5.86) in coinfected patients. The only factors associated with severe liver events at 6 months were baseline HT and HCV coinfection. CONCLUSION: The incidence of severe hepatic events in HIV-positive patients receiving a HAART regimen including LPV/r was very low, even in coinfected patients. HCV coinfection and baseline HT were the only factors associated with severe liver events. LPV/r can be considered a safe and well-tolerated option in HIV patients with hepatotropic virus coinfections.

Clinical and virological efficacy of etravirine plus two active Nucleos(t)ide analogs in an heterogeneous HIV-infected population.

UNLABELLED: Etravirine (ETV) is recommended in combination with a boosted protease inhibitor plus an optimized background regimen for salvage therapy, but there is limited experience with its use in combination with two nucleos(t)ide reverse-transcriptase inhibitors (NRTIs). This multicenter study aimed to assess the efficacy of this combination in two scenarios: group A) subjects without virologic failure on or no experience with non-nucleoside reverse-transcriptase inhibitors (NNRTIs) switched due to adverse events and group B) subjects switched after a virologic failure on an efavirenz- or nevirapine-based regimen. The primary endpoint was efficacy at 52 weeks analysed by intention-to-treat. Virologic failure was defined as the inability to suppress plasma HIV-RNA to <50 copies/mL after 24 weeks on treatment, or a confirmed viral load >200 copies/mL in patients who had previously achieved a viral suppression or had an undetectable viral load at inclusion. Two hundred eighty seven patients were included. Treatment efficacy rates in group A and B were 88.0% (CI95, 83.9-92.1%) and 77.4% (CI95, 65.0-89.7%), respectively; the rates reached 97.2% (CI95, 95.1-99.3%) and 90.5% (CI95, 81.7-99.3), by on-treatment analysis. The once-a-day ETV treatment was as effective as the twice daily dosing regimen. Grade 1-2 adverse events were observed motivating a treatment switch in 4.2% of the subjects. In conclusion, ETV (once- or twice daily) plus two analogs is a suitable, well-tolerated combination both as a switching strategy and after failure with first generation NNRTIs, ensuring full drug activity. TRIAL REGISTRATION: ClinicalTrials.gov NCT01437241.

Prevalence and risk factors for abnormal liver stiffness in HIV-infected patients without viral hepatitis coinfection: role of didanosine.

BACKGROUND: Unexpected cases of severe liver disease in HIV-infected patients have been reported and an association with didanosine (ddI) has been suggested. Transient elastography (TE) might detect patients harbouring such a condition. Our objective was to search for the presence of abnormal liver stiffness (LS) in a cohort of HIV-infected patients without HBV or HCV coinfection and to assess the related factors. METHODS: A cross-sectional prospective study was conducted. LS was assessed by TE in 258 HIV-infected patients without HBV or HCV coinfection and with no evidence of acute hepatotoxicity or other origins of liver disease. LS values > or =7.2 kPa were considered abnormal. Multivariate analyses were performed to identify factors associated with abnormal LS. RESULTS: Abnormal LS was observed in 29 (11.2%) patients. A total of 18 (16.4%) patients previously treated with ddI and 11 (7.4%) of those who never received ddI had LS values > or =7.2 kPa (P=0.02). The prevalence of abnormal LS was higher in patients previously treated with abacavir than in those who had never received abacavir (15 [21.7%] versus 14 [7.4%]; P=0.001). After multivariate analyses, age (adjusted odds ratio [AOR] 1.05, 95% confidence interval [CI] 1.002-1.1; P=0.004) alcohol intake >50 g/day (AOR 7.2, 95% CI 2.6-19.7; P<0.0001), CD4(+) T-cell count <200 cells/ml (AOR 3.4, 95% CI 1.06-11.007; P=0.03), time on ddI treatment (AOR 1.31, 95% CI 1.12-1.52; P=0.001) and previous abacavir exposure (AOR 3.01, 95% CI 1.18-7.67; P=0.02) were independently associated with abnormal LS. CONCLUSIONS: The prevalence of abnormal LS in HIV-infected patients without HBV or HCV coinfection is substantial. Long-term exposure to ddI is a major cause of liver damage in these patients.

Efficacy of low-dose boosted saquinavir once daily plus nucleoside reverse transcriptase inhibitors in pregnant HIV-1-infected women with a therapeutic drug monitoring strategy.

The efficacy of low-dose, ritonavir-boosted saquinavir (SQV/rtv) once daily plus 2 nucleoside retrotranscriptase inhibitors (NRTIs) in pregnant human immunodeficiency virus (HIV)-1-infected women was prospectively evaluated, ensuring a SQV minimum concentration (Cmin) >/=100 ng/mL with a therapeutic drug monitoring strategy. The primary clinical endpoint was the percentage of women with an HIV-RNA viral load (VL) of <50 copies/mL at the time of delivery. Forty-nine pregnancy episodes were included, with a median CD4 count and VL of 441/muL and 3710 copies/mL, respectively. Two patients were lost to follow-up and 1 patient discontinued treatment because of abdominal discomfort. SQV levels were in excess of the target Cmin in 43 of 46 episodes (93.4%) in which the end of pregnancy was reached on 1200/100 mg daily. The dosage was increased to 1600/100 mg in the remaining 3 episodes to achieve the target levels. By an intention-to-treat analysis, VL was undetectable at delivery in 43 episodes (87.7%; 95% confidence interval, 78.5-96.9) after a median of 18 weeks of treatment (range, 3-39). In the 3 episodes remaining, VLs of 110,400 copies/mL and no available data were observed after only 3 weeks of treatment. Mild adverse events attributable to SQV/rtv occurred in 6 of 49 pregnancies (12.2%). No cases of HIV vertical transmission were observed. The pharmacokinetics, efficacy, and tolerability of this regimen suggest that once-daily low-dose boosted SQV may be considered an appropriate option in PI-naive or limited-PI-experienced HIV-infected pregnant women. Nevertheless, therapeutic drug monitoring is advisable to maintain appropriate levels throughout pregnancy.

Relationship between 1,25-dihydroxycholecalciferol levels and functional outcome after hip fracture in elderly patients.

A prospective study was performed in 109 patients with osteoporotic hip fracture to verify the relationship between 1,25-dihydroxycholecalciferol levels at admission and functional recovery in elderly patients with hip fracture. 47.7% of all the patients had 1,25-dihydroxycholecalciferol levels below the reference values of our laboratory. At 1 year of the fracture only 33 patients (30.3%) had recovered the functional level they had before the fracture. In the bivariate analysis, a statistically significant relationship was found between reduced 1,25-dihydroxycholecalciferol levels and a poorer functional recovery 1 year after the fracture was sustained. A multivariate analysis showed a significant relationship between 1,25-dihydroxycholecalciferol levels and absolute dependence of the patient 1 year after the fracture (P = 0.005; OR 6.97: CI- 1.77-27.41).

Clinical characteristics of melon (Cucumis melo) allergy.

BACKGROUND: Although melon is a frequent allergy-eliciting fruit, allergic reactions to melon have rarely been reported. OBJECTIVE: To evaluate and describe the clinical characteristics of melon allergy in melon-allergic patients. MATERIALS AND METHODS: We evaluated patients allergic to melon and a control group of patients allergic to pollen. The diagnosis of melon allergy was based on a convincing clinical history, positive skin test results (prick-by-prick test), and positive results on oral challenge tests to melon. RESULTS: A total of 161 patients were included in the study: 66 in the melon allergy group and 95 in the pollen control group. The melon allergy group included 35 female and 31 male patients with a mean age of 26.6 +/- 2.7 years (range, 5-61 years). Although all patients had oral symptoms, 13 (19.7%) of the patients had extraoral symptoms and none experienced generalized urticaria or anaphylaxis. Excluding other Cucurbitaceae fruits, peach, fig, and kiwi most frequently elicited positive skin test results and symptoms. Up to 23% of melon-allergic patients had a concomitant latex sensitization. Melon allergy was especially linked to pollen allergy, since all the melon-allergic patients were also allergic to pollen. Some differential features with respect to the pollen allergy control group were a higher prevalence of asthma (odds ratio [OR], 2.13; P < 0.05) and a statistical increase in the frequency of sensitization to several tree and weed pollens, including Ulmus (OR, 42.8) and Ambrosia (OR, 22.4). CONCLUSION: The most important conditions linked to melon allergy are pollen allergy (100%), allergy to other nonrelated fruits, mainly peach (up to 62%), and latex sensitivity (up to 23%). Some differential features of the pollinosis in melon allergy were a higher prevalence of asthma and a higher frequency of sensitization to several weed and tree pollens.