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Hemophagocytic lymphohistiocytosis (HLH) is an aggressive and life-threatening syndrome characterized by excessive immune activation. We analyzed the presentation, diagnosis and prognosis of our cohort of HLH-Leishmaniacases.

Very limited labelled indications have been approved for the newer antimicrobials. Data on the clinical uses, efficacy and safety of dalbavancin are scarce, thus here we sought to describe our clinical experience. 16-month observational prospective study was performed. 19 (86%) were used under off-label indications. 10 (46%) for osteoarticular infections, 5 (23%) bloodstream infections and 3 (14%) endocarditis. To highlight, one patient received dalbavancin as long-term suppressive therapy. Most frequent use reasons were promptly hospital discharge, 11 (65%), and the presence of resistant organisms involving limited treatment options, 5 (23%). Successful outcome was observed in >95% of the patients and only 1 (4.5%) adverse event was reported. Further evidence beyond labelled indications is urgently needed. Despite the limitations, dalbavancin appears to be a safe and efficient option for adult patients who have tried and/or failed other therapies due to multidrug-resistant Gram-positive organisms.

Background Gender-specific data on the management of HIV infection are scarce. Further, an increase in the proportion of new HIV diagnoses in older persons has been observed. Using data from the CoRIS cohort, we compared immunovirological responses and survival in HIV-infected men and women who started their first combination anti-retroviral therapy (cART) when aged

El objetivo principal del estudio ha sido valorar si la penetración de antibióticos se ve influenciada por la perfusión tisular disminuida en pacientes con isquemia de miembros, reduciendo la concentración alcanzada en tejidos por debajo de los puntos de corte (breakpoints)de la concentración mínima inhibitoria (CMI) de los antimicrobianos utilizados para diferentes patógenos.

La incidencia de la tuberculosis (TB) en la población autóctona en España continúa descendiendo, aumentando la proporción de casos en extranjeros. El objetivo de este estudio fue identificar las características diferenciales de la TB en la población inmigrante con respecto a la autóctona en el Área de Salud Sur de Granada, España.

We aimed to characterize non-AIDS events (NAEs) occurring in newly diagnosed HIV-infected patients in a contemporary cohort.

Background This study evaluates the added benefit when estimating antiretroviral drug resistance of combining all available resistance test results in a cumulative genotype relative to using the latest genotype alone.Methods The prevalence of resistance and genotypic sensitivity scores (GSS) predicted by the latest and the cumulative genotype, together with virological outcomes after the latest genotype, were measured in treatment-experienced patients who underwent=2 resistance tests in 1999–2008.Results Comparing the latest with the cumulative genotype in 227 patients, 4 (1.7%) versus 0 (0.0%) showed no major resistance mutations, whereas 74 (32.6%) versus 46 (20.3%), 88 (38.8%) versus 76 (33.5%) and 61 (26.9%) versus 105 (46.3%) showed single-class, dual-class and triple-class resistance mutations, respectively. The median (IQR) number of fully or partially active drugs was 6 (5–6) versus 5 (4–6) for the nucleoside/nucleotide reverse transcriptase inhibitors, 3 (1–3) versus 1 (1–3) for the non-nucleoside reverse transcriptase inhibitors and 7 (7–7) versus 7 (7–7) for the protease inhibitors, respectively. Among 163 patients who started a new regimen after the latest genotype, both the latest and the cumulative GSS were predictive of early (=24 weeks) virological responses. The GSS decreased by median 1 unit (IQR 0.5–1.0) in the cumulative genotype and larger differences relative to the latest genotype corresponded to smaller decreases in viral load.Conclusions The cumulative genotype offers a more comprehensive evaluation of the burden of resistance. This approach can guide small but appreciable improvements in the selection of antiretroviral regimens for treatment-experienced patients.

ABSTRACTThe effect of hepatic impairment on fosamprenavir/ritonavir pharmacokinetics was investigated. Sixty human immunodeficiency virus type 1-infected subjects, including 13, 20, and 10 subjects with mild, moderate, and severe hepatic impairment, respectively, and a comparator group of 17 subjects with normal hepatic function, were enrolled. Subjects with normal hepatic function received fosamprenavir at 700 mg plus ritonavir at 100 mg twice daily, whereas subjects with hepatic impairment received adjusted doses in anticipation of increased exposures. For subjects with mild hepatic impairment, the studied regimen of fosamprenavir 700 mg twice daily plus ritonavir 100 mg once daily delivered 17% higher values for the maximum plasma amprenavir concentration at the steady state (Cmax), 22% higher values for the area under the plasma concentration versus time curve over the dosing interval at the steady state [AUC(0-τ)], similar values for the concentration at the end of the dosing interval (Cτ), and 114% higher unbound Cτvalues. For subjects with moderate hepatic impairment, the studied dosage regimen of fosamprenavir at 300 mg twice daily plus ritonavir at 100 mg once daily delivered 27% lower plasma amprenavir Cmaxvalues, 27% lower AUC(0-24)values, 57% lower Cτvalues, and 21% higher unbound amprenavir Cτvalues. For subjects with severe hepatic impairment, the studied dosage regimen of fosamprenavir at 300 mg twice daily plus ritonavir at 100 mg once daily delivered 19% lower plasma amprenavir Cmaxvalues, 23% lower AUC(0-24)values, 38% lower Cτvalues, and similar unbound amprenavir Cτvalues. With a reduced ritonavir dosing frequency of 100 mg once daily, the plasma ritonavir AUC(0-24)values were 39% lower, similar, and 40% higher for subjects with mild, moderate, and severe hepatic impairment, respectively. The results of the study support the use of reduced fosamprenavir/ritonavir doses or dosing frequencies in the treatment of patients with hepatic impairment. No significant safety issues were identified; however, plasma amprenavir and ritonavir exposures were more variable in subjects with hepatic impairment, and those patients should be closely monitored for safety and virologic response.

Cohort studies have shown that highly active antiretroviral therapy (HAART) can improve liver-related mortality in HIV/hepatitis C virus (HCV)-coinfected patients. A reduction in the accelerated liver fibrosis progression observed in HIV infection induced by HAART could explain these findings. A few studies have assessed the impact of HAART on liver fibrosis, but with contradictory results. Therefore, we evaluated the associations between the use of different antiretroviral drug classes and HAART combinations, and liver fibrosis in HIV-infected patients with chronic hepatitis C. Six hundred and eighty-three HIV/HCV-coinfected patients, who underwent a liver biopsy and who had not received anti-HCV treatment were included. Age at HCV infection <23 years (adjusted odds ratio [AOR]=0.7, 95% confidence interval [95% CI]=0.3-0.9, P=0.05) and protease inhibitor (PI)-based HAART versus no use of HAART (AOR=0.5, 95% CI=0.3-0.9, P=0.01) were negatively associated with advanced fibrosis (=F3). PI-based HAART versus no use of HAART (AOR=0.4, 95% CI=0.2-0.7, P=0.001) was negatively associated with fibrosis progression rate =0.2 units/year and independently of age at HCV infection and CD4+T-cell counts. Fifteen (17%) patients treated only with PIs and zidovudine plus lamivudine showed =F3, compared with 65 (37%) patients without HAART (P=0.001). Forty (31%) patients on PI and stavudine plus lamivudine showed =F3 (P=0.3, when compared with patients with no HAART). The use of PI-based HAART in HIV/HCV-coinfected patients is associated with less severe fibrosis and slower progression of fibrosis. The nucleoside analogue backbone in a HAART regimen may influence this association.