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

Necrotizing Pneumonia Caused by Panton-Valentine Leucocidin-Producing Staphylococcus aureus Originating from a Bartholin's Abscess

Background. Panton-Valentine leukocidin (PVL-)producing Staphylococcus aureus is emerging as a serious problem worldwide. There has been an increase in the incidence of necrotizing lung infections in otherwise healthy young people with a very high mortality associated with these strains. Sporadic severe infectious complications after incision of Bartholin's abcesses have been described but involvement of S. aureus is rare. Case report. We present a 23-year-old apparently healthy female patient without any typical predisposing findings who developed severe sepsis with necrotizing pneumonia and multiple abscesses following incision of a Bartholin's abscess. Methicillin-sensitive S. aureus harbouring Panton-Valentine leucocidin genes were cultured from the abscess fluid, multiple blood cultures and a postoperative wound swab. Aggressive antibiotic therapy with flucloxacillin, rifampicin and clindamycin, drainage and intensive supportive care lead finally to recovery. Conclusions. S. aureus, in particular PVL-positive strains, should be considered when a young, immunocompetent person develops a fulminant necrotizing pneumonia. Minor infections—such as Bartholin's abscess—can precede this life-threating syndrome. Bactericidal antistaphylococcal antibiotics are recommended for treatment, and surgical procedures may become necessary

Phase II Study of Vicriviroc versus Efavirenz (both with Zidovudine/Lamivudine) in Treatment-Naive Subjects with HIV-1 Infection

Background. Vicriviroc (VCV) is a CCR5 antagonist with nanomolar activity against human immunodeficiency virus (HIV) replication in vitro and in vivo. We report the results of a phase II dose-finding study of VCV plus dual nucleoside reverse-transcriptase inhibitors (NRTIs) in the treatment-naive HIV-1-infected subjects. Methods. This study was a randomized, double-blind, placebo-controlled trial that began with a 14-day comparison of 3 dosages of VCV with placebo in treatment-naive subjects infected with CCR5-using HIV-1. After 14 days of monotherapy, lamivudine/zidovudine was added to the VCV arms; subjects receiving placebo were treated with efavirenz and lamivudine/zidovudine; the planned treatment duration was 48 weeks. Results. Ninety-two subjects enrolled. After 14 days of once-daily monotherapy, the mean viral loads decreased from baseline values by 0.07 log10 copies/mL in the placebo arm, 0.93 log10 copies/mL in theVCV25 mg arm, 1.18 log10 copies/mL in the VCV 50 mg arm, and 1.34 log10 copies/mL in the VCV 75 mg arm (P < .001 for each VCV arm vs. the placebo arm). The combination-therapy portion of the study was stopped because of increased rates of virologic failure in the VCV 25 mg/day arm (relative hazard [RH], 21.6; 95% confidence interval [CI], 2.8-168.9) and the VCV 50 mg/day arm (RH, 11.7; 95% CI, 1.5-92.9), compared with that in the control arm. Conclusion. VCV administered with dual NRTIs in treatment-naive subjects with HIV-1 infection had increased rates of virologic failure, compared with efavirenz plus dual NRTIs. No treatment-limiting toxicity was observed. Study of higher doses of VCV as part of combination therapy is warrante

Différences selon le sexe dans l’âge d’apparition, la symptomatologie et l’évolution de la schizophrénie

Les différences selon le sexe dans l'âge d'apparition, la symptomatologie et l'évolution de la schizophrénie sont examinées par une analyse de cas dûment enregistrés et par une enquête directe à partir d'un échantillon représentatif de patients hospitalisés pour la première fois. La découverte centrale que les hommes deviennent schizophrènes à un âge plus précoce que les femmes se confirme après avoir écarté d'autres interprétations dues à des distorsions d'échantillonnage, à des différences d'intervalle entre l'apparition effective de la maladie et la première admission à l'hôpital, à des différences par sexe dans le développement des symptômes ou à d'autres facteurs confondants. Si l'on cherche les causes de ces différences entre hommes et femmes, il semble que les perturbations du début du développement social doivent être comprises alors comme les conséquences d'une schizophrénie débutante plutôt que comme ses conditions d'apparition. Il en ressort le besoin de modèles expliI catifs qui permettent de tester empiriquement les hypothèses sur le développement spécifique de la schizophrénie dans l'un et l'autre sexe.Gender differences in age at onset, symptomatology and course of schizophrenia are examined by analyzing case register data and by direct investigation of a representative sample of first-admitted patients. The main finding that males fall ill at an earlier age than females can be confirmed even after ruling out other interpretations due to sample bias, different time span between real onset and first hospital admission, gender differences in symptom development or other confounding factors. When looking for causes of these gender differences it seems that disturbances in early social development must be understood as a consequence of beginning schizophrenia rather than a prerequisite. The need for explanatory models is stressed that allow for the empirical testing of hypotheses concerning gender specific development of schizophrenia

Fatal case due to methicillin-resistant Staphylococcus aureus small colony variants in an AIDS patient.

We describe the first known case of a fatal infection with small colony variants of methicillin-resistant Staphylococcus aureus in a patient with AIDS. Recovered from three blood cultures as well as from a deep hip abscess, these variants may have resulted from long-term antimicrobial therapy with trimethoprim/sulfamethoxazole for prophylaxis of Pneumocystis carinii pneumonia