Once-daily saquinavir (SAQ)/ritonavir (RTV) (2000/100 mg) with abacavir/lamivudine (600/300 mg) or tenofovir/emtricitabine (245/300 mg) in naïve patients

Poster presentation: Background In the past years, once-daily (QD) dosing of antiretroviral combination therapy has become an increasingly available treatment option for HIV-1+ patients. Methods Open label study in which HIV-1+ patients treated with SAQ/RTV (1000/100 mg BID) and two NRTIs with HIV-RNA-PCR < 50 copies/ml were switched to SAQ/RTV(2000/100 mg QD) with unchanged NRTI-backbone. CD4-cells, HIV-RNA-PCR, SAQ and RTV drug-levels and metabolic parameters were compared. Summary of results 17 patients (15 male, 42 years), median CD4 456 ± 139/micro l were included so far. The median follow-up time is 4 months. The HIV-RNA-PCR remained <50 copies/ml for all patients. Fasting metabolic parameters remained unchanged. The SAQ AUC 0–12 h were significantly higher when given QD vs. BID (median 29,400 vs. 18,500 ng*h/ml; p = 0.009), whereas the Cmin, Cmax and AUC was lower for RTV when given QD vs. BID (7,400 vs. 11,700 ng*h/ml; p = 0.02). Conclusion In this ongoing study SAQ/RTV (2000/100 mg QD) was well tolerated and demonstrated higher SAQ and lower RTV drug levels as compared to the BID dosing schedule. (Table 1 and Figure 1.

Efficacy and safety of TDF/FTC-containing first-line HAART in clinical practice – 2-year data from the German Outpatient Cohort

Poster presentation: Purpose of the study First-line HAART with tenofovir DF (TDF) and FTC in pivotal trials has been associated with high efficacy and good tolerability. However, real-life clinical practice often differs from clinical trials due to co-morbidities, co-infections, and less intensive clinical monitoring. To evaluate efficacy and safety of first-line HAART in a day-to-day setting, this Gilead-sponsored non-interventional cohort was established. Methods Between July 2005 and August 2006, 533 HIV-1 infected antiretroviral-naïve patients from 50 German centres enrolled in this non-interventional cohort. All patients were followed every 3 months for 3 years to monitor efficacy (viral load [VL], CD4), tolerability, renal safety, regimen changes and resistance profile. All patients received TDF+FTC as a single tablet (Truvada, TVD) in combination with either an NNRTI or PI/r as their first antiretroviral regimen. Summary of results As of June 2008, 2 years of therapy have been documented for 330/533 (62%) patients. At treatment initiation, 81% were male; median age was 39 years; clinical AIDS diagnosis was documented in 22%; 47% started therapy with CD4 <200 cells/mm3. TVD was combined with an NNRTI (43%) or a PI/r (57%). After 24 months, in an As-Treated (AT) analysis, 85% patients achieved a VL <50 copies/ml (VL <500 copies/ml: 97%), median CD4 count increased from 217 at baseline to 450 cells/mm3 (IQR: 325–608). Truvada showed a good safety profile; 76 adverse events (AEs) of any grade were reported in 66/533 patients (12%); six of these were judged serious. Fourteen (2.6%) patients discontinued TVD due to AEs. Renal abnormalities of any grade were reported in 10 patients (1.9%). Virological failure was documented in nine patients, of which eight were genotyped; M184V/I was detected in three, K65R in two patients. Conclusion During 2 years of follow-up, the overall safety of TVD was good; renal AEs of any grade were reported in 1.9% of patients. K65R was detected in two patients. First-line HAART with TVD plus an NNRTI or PI/r in clinical practice showed comparable efficacy to that observed in controlled clinical trials

Virological and immunological response to three boosted protease inhibitor regimens

Poster presentation: Purpose of the study To compare the virological, immunological and clinical response to three boosted double protease inhibitor (PI) regimens of saquinavir and ritonavir in combination with lopinavir (LOPSAQ), atazanavir (ATSAQ) or fosamprenavir (FOSAQ) without reverse transcriptase inhibitors (RTI) in HIV-positive patients with limited RTI treatment options. ..

High effectiveness of recommended first-line antiretroviral therapies in Germany: a nationwide, prospective cohort study

Purpose Current German/Austrian antiretroviral treatment guidelines recommend more than 20 combination regimens for first-line therapy, without a preference. Regimens include two nucleoside reverse transcriptase inhibitors (NRTIs) plus either an integrase strand transfer inhibitor (INSTI), a non-NRTI (NNRTI) or a boosted protease inhibitor (PI). The objective was to examine the outcomes of recommended first-line ART in Germany. Methods This nationwide observational study included treatment-naive chronically HIV-1 infected patients receiving one of the recommended first-line regimens. Patients were allocated to three arms (INSTI, NNRTI, PI) and were prospectively followed for 24 months. Delayed treatment initiation was defined by a baseline CD4 T-cell count of < 350/mu l or CDC clinical stage C. Results Among a total of 434 patients enrolled, virologic failure was rare and occurred in 4.3% (6/141) in the PI arm, in 3.3% (4/122) in the NNRTI arm and in 0.6% (1/171) in the INSTI arm (p = 0.10). De novo drug resistance mutations developed in only two patients in the NNRTI arm. Nonetheless, treatment modifications were frequent (51%) and mostly performed for strategic reasons. Retention on all initial compounds at month 24 was 64%, 49%, and 22% in the INSTI, NNRTI and PI arms respectively. Delayed treatment initiation was common (47%) and more frequently observed in patients in the PI arm. It was not associated with virological failure. Conclusion High efficacy and low virological failure rates were observed with recommended first-line regimens independent of delayed treatment initiation, chosen regimen and subsequent treatment modifications, demonstrating the validity of the current treatment guidelines

First test of cold edgeless silicon microstrip detectors

Silicon microstrip detectors will provide the forward tracking in the TOTEM experiment at the LHC. To allow efficient tracking closest to the beam ( approximately equals 1 mm) these detectors should be sensitive up to their physical edge (i.e. edgeless). Edgeless (without guard rings) microstrip planar detectors can be operated at cryogenic temperatures (about 130 degree K) where leakage currents due to the active edge are drastically reduced. A silicon microstrip prototype, cut perpendicular to the strips, has been tested with a pion beam at CERN to study its efficiency close to the edge by using reference tracks from a simple silicon telescope. Results indicate that the detector measures tracks with good efficiency up to the physical edge of the silicon

Update on the “Choosing Wisely” initiative in infectious diseases in Germany

Purpose!#!The Choosing Wisely!##!Methods!#!The recommendations of the DGI are part of the 'Klug entscheiden' initiative of the German Society of Internal Medicine (DGIM). Topics for the new items were suggested by members of the DGI, checked for scientific evidence and consented within the DGI and the DGIM before publication.!##!Results!#!The new recommendations are: (1) individuals with immune-suppression, advanced liver cirrhosis or renal insufficiency should receive a dual pneumococcal vaccination. (2) In case of positive blood cultures with Candida spp. thorough diagnostics and treatment should be initiated. (3) In case of suspected meningitis, adult patients should receive dexamethasone and antibiotics immediately after venipuncture for blood cultures and before potential imaging. (4) In case of suspected meningitis a CT scan before lumbar puncture should not be ordered-except for symptoms indicating high CSF pressure or focal brain pathology or in cases of severe immune-suppression. (5) In patients with suspected severe infections, a minimum of two pairs of blood cultures should be drawn using separate venipunctures prior to antibiotic therapy-regardless of body temperature. There is no need of a minimum time interval in between the blood draws.!##!Conclusion!#!Applying these new Choosing Wisel

OF-Pelvis classification of osteoporotic sacral and pelvic ring fractures

Objectives Osteoporotic fractures of the pelvis (OFP) are an increasing issue in orthopedics. Current classification systems (CS) are mostly CT-based and complex and offer only moderate to substantial inter-rater reliability (interRR) and intra-rater reliability (intraRR). MRI is thus gaining importance as a complement. This study aimed to develop a simple and reliable CT- and MRI-based CS for OFP. Methods A structured iterative procedure was conducted to reach a consensus among German-speaking spinal and pelvic trauma experts over 5 years. As a result, the proposed OF-Pelvis CS was developed. To assess its reliability, 28 experienced trauma and orthopedic surgeons categorized 25 anonymized cases using X-ray, CT, and MRI scans twice via online surveys. A period of 4 weeks separated the completion of the first from the second survey, and the cases were presented in an altered order. While 13 of the raters were also involved in developing the CS (developing raters (DR)), 15 user raters (UR) were not deeply involved in the development process. To assess the interRR of the OF-Pelvis categories, Fleiss' kappa (kappa(F)) was calculated for each survey. The intraRR for both surveys was calculated for each rater using Kendall's tau (tau(K)). The presence of a modifier was calculated with kappa(F) for interRR and Cohen's kappa (kappa(C)) for intraRR. Results The OF-Pelvis consists of five subgroups and three modifiers. Instability increases from subgroups 1 (OF1) to 5 (OF5) and by a given modifier. The three modifiers can be assigned alone or in combination. In both surveys, the interRR for subgroups was substantial: kappa(F) = 0.764 (Survey 1) and kappa(F) = 0.790 (Survey 2). The interRR of the DR and UR was nearly on par (kappa(F) Survey 1/Survey 2: DR 0.776/0.813; UR 0.748/0.766). The agreement for each of the five subgroups was also strong (kappa(F) min.-max. Survey 1/Survey 2: 0.708-0.827/0.747-0.852). The existence of at least one modifier was rated with substantial agreement (kappa(F) Survey 1/Survey 2: 0.646/0.629). The intraRR for subgroups showed almost perfect agreement (tau(K) = 0.894, DR: tau(K) = 0.901, UR: tau(K) = 0.889). The modifier had an intraRR of kappa(C) = 0.684 (DR: kappa(C) = 0.723, UR: kappa(C) = 0.651), which is also considered substantial. Conclusion The OF-Pelvis is a reliable tool to categorize OFP with substantial interRR and almost perfect intraRR. The similar reliabilities between experienced DRs and URs demonstrate that the training status of the user is not important. However, it may be a reliable basis for an indication of the treatment score