The purpose of this study was to compare treatment and outcome of patients with Waldenström's macroglobulinemia (WM) in four private oncology practices (PP) and a university hospital (UH) in southwest Germany. We retrospectively reviewed the charts of all patients with WM of the last two decades of four PP in Mannheim, Heidelberg, Karlsruhe, and Speyer and the Department of Hematology of the University of Heidelberg. One hundred seventy patients could be identified, 74 from PP, 96 from the UH. Median age was 63.3 years. Patients from PP were older (median 65.3 vs. 62.5 years, p = 0.01). Only 54 % of patients from PP have received treatment during the observation time, as compared to 78.1 % of the UH (p < 0.001). In PP, 35 % of treated patients have received rituximab, as compared to 62.6 % of the patients of the UH (p < 0.001). Sixty percent of treated patients of PP have received bendamustine, as compared to only 8 % of the patients of the UH (p < 0.001). Time to first treatment was significantly shorter in patients from the UH compared to PP (median 13.7 vs. 52.9 months, p = 0.05). A trend towards a better overall survival was observed for patients treated with a rituximab-containing first-line regimen. The International Prognostic Scoring System for WM had significant prognostic value. Median overall survival was 25.0 years and did not differ between PP and UH. Despite different treatment strategies between PP and UH today overall survival of patients with WM is excellent, and better than previously reported.

Aim: For several years Nonnucleoside reverse transciptase inhibitors (NNRTIs) in antiretroviral therapy have been associated with hepatic side effects. Particularly the hepatotoxic potential of Nevirapine is well analysed today. We performed a prospective, multicenter study to compare the hepatotoxicity of Efavirenz (EFV) with that of Nevirapine (NVP) and to investigate further risk factors.Material and Methods: The study, included HIV-1-infected patients from five clinics and private medical practices in south-western Germany who initiated an antiretroviral therapy with NVP or EFV between July 1998 and December 2001. Among 296 patients in total, 151 received EFV and 145 received NVP. Laboratory tests during the course of treatment included liver enzymes, HIV-RNA and CD4 cell-count. Additionally, signs of clinical hepatitis were recorded. Hepatotoxicity was graded in the manner of Sulkowsky et al. ( 000), Who used a scale modified from that of the AIDS Clinical Trials Group.Results: Hepatitis C virus and hepatitis B virus were detected in 10.1% and 4.1% of patients, respectively. The overall rate of severe hepatotoxicity (grade 3 to 4 elevations in aspartate aminotransferase and/or alanine aminotransferase) was 2 of 151 (1.3%) in patients prescribed EFV and 3 of 145 (2.1%) in patients prescribed NVP. Mild-to-moderate hepatotoxicity (grade 2 elevation) was observed in 6.0% (EFV and 3.4% (NVP) of patients. Incidence of mild-to-moderate and severe hepatotoxicity did not differ significantly between the study groups. 3 of 14 patients (2.1%) with grade 2 elevation of liver enzymes (LEE) and 4 of 5 patients (80%) with grade 3 to 4 LEE were symptomatic. Only risk factor for the development of mild-to-moderate hepatotoxicity was hepatitis C coinfection.Conclusion: Increases of liver enzymes during therapy with NVP or EFV are not unusual, but are mostly mild-to-moderate and asymptomatic. LEE occurs just as frequent in patients prescribed ETV as in patients prescribed NVP.

OBJECTIVE:To evaluate the long-term effects of antiretroviral treatment (ART) interruptions on metabolic, immunological, virological and clinical outcomes in chronically HIV-1 infected patients.METHODS:Multi-centric, prospective, controlled 24-month cohort study in HIV-1 infected patients interrupting ART once or several times and for at least two weeks. Patients were compared to a frequency-matched control group continuing on ART.RESULTS:A total of 399 HIV-1 infected patients were included, among them 133 patients with treatment interruption (TI) and 266 control patients. Baseline characteristics were well matched. Median baseline CD4 cell count was 379/microl in TI-patients and 410/microl in control patients (p = ns). Median duration of the first TI was 1.1 months, and 37 % of patients had two or further TI's. Whereas CD4 cell count in control patients had increased significantly by a median of 67/microl at month 24 (p<0.0001), median CD4 cell count at month 24 in the TI-patients did not differ significantly from baseline. However, two-year AIDS-free survival was not significantly different between TI- and control patients. Liver enzymes and blood lipids improved significantly during TI.CONCLUSION:TI was associated with a significant immunological disadvantage at 24-month follow-up compared to continued ART. In this relatively immunocompetent cohort, however, TI's did not lead to an increased risk of disease progression within two years of follow-up.

Efavirenz und Nevirapin zählen zu den oft verwendeten Medikamenten bei HIV-Infektion. Wichtige Nebenwirkung dieser Substanzen sind Arzneimittelexantheme. In der vorliegenden Studie werden die Exantheme als häufigste Nebenwirkung beider Substanzen charakterisiert.

Efavirenz and nevirapine are frequently used drugs in antiretroviral therapy. Rashes are common side effects of these drugs. In this study, we examined the characteristics of efavirenz- and nevirapine-associated rashes. This prospective nonrandomized multicenter study included 662 HIV-infected patients (efavirenz: 325, nevirapine: 337) to determine incidence, duration, cross-reactivity, and outcome upon reexposure. Of the treated patients, 4.5% (n=30) developed rashes (nevirapine: 2.4% and efavirenz: 6.4%). In four patients treatment was not interrupted. Three patients were re-exposed to the initial drug without any side effects. Therapy with nevirapine or efavirenz does not have to be interrupted if rashes exhibit no blistering, mucosal manifestations, or systemic signs.

The non-nucleoside reverse transcriptase inhibitors (NNRTIs) efavirenz (EFV) and nevirapine (NVP) taken in combination with nucleoside reverse transcriptase inhibitors (NRTIs) have both shown to be just as highly effective as protease inhibitors (PIs) in reducing viral load in patients infected with HIV. Our study compares the performance of these two NNRTIs with each other. This was a non-randomized, prospective, two-arm, multi-centre trial. We evaluated all patients with an EFV- or NVP-containing antiretroviral regimen. The primary endpoint was the difference in success rates defined as a viral load of =50 copies/mL at week 48. chi(2)-tests were used for naïve and pretreated patients using intention-to-treat (ITT) and on-treatment analysis. As secondary endpoints, a viral load of =500 copies/mL and CD4 count at week 48 for naïve patients were evaluated. A Cox regression was used to adjust for prespecified covariates. We included 662 patients (NVP 337, EFV 325). The difference in success rates in the ITT analysis was 4.5% ( -11.5%, 19.0%), P=0.578. Pretreated patients with a triple therapy show a difference of 10.1 (-0.3, 20.6), P=0.056. Non-significant results appeared for all secondary analyses. In this trial, no difference between EFV and NVP in combination with NRTI backbone therapy can be shown, regarding viral load. Further randomized studies are necessary to evaluate possible differences.

Efavirenz and nevirapine are frequently used drugs in antiretroviral therapy. Rashes are common side effects of these drugs. In this study, we examined the characteristics of efavirenz- and nevirapine-associated rashes.This prospective nonrandomized multicenter study included 662 HIV-infected patients (efavirenz: 325, nevirapine: 337) to determine incidence, duration, cross-reactivity, and outcome upon reexposure.Of the treated patients, 4.5% (n=30) developed rashes (nevirapine: 2.4% and efavirenz: 6.4%). In four patients treatment was not interrupted. Three patients were reexposed to the initial drug without any side effects.Therapy with nevirapine or efavirenz does not have to be interrupted if rashes exhibit no blistering, mucosal manifestations, or systemic signs.

PURPOSE:To show Didanosin in a new formulation as a once-a-day capsula as a well-tolerated and effective HIV-therapy when used in a protease sparing regimen including genotypic resistance pattern in blood, semen and cerebrospinal fluid before and during treatment.METHOD:Two groups of 58 patients, each containing 9 patients who had not been previously treated with any antiretroviral medication, and 49 patients heavily pretreated for 3,7 (DDI group) and 2,8 (non-DDI group) years, have been followed up for at least half a year. A group of 24 patients taking a special combination of Didanosin plus Efavirenz and Stavudine have been analysed with genotypic resistance testing concerning viral load response and resistance pattern under therapy.RESULTS:Suppression of plasma HIV-1 RNA to <50 copies/mL and <500 copies/mL in the DDI group was achieved in 74% and 84% of the pretreated patients, respectively, and in 100% of the naive patients after 24 weeks. In the non-DDI group suppression was achieved in 59% and 69% of the pretreated patients, respectively, and in also 100% of the naive patients. The viral load reduction in the DDI containing regimen at week 24 was 1.7 log subset 10 for the pretreated and 3,4 log subset 10 for the naive patients. In the non-DDI group, the reduction was 1.5 for the pretreated and 4,0 for the naive patients. CD4 cell counts increased from 440 to 517 cells/microL at week 24 for the pretreated, and from 171 to 289 for the naive patients in the DDI containing regimen. In the other group, cells increased from 396 to 406 for the pretreated and from 155 to 321 for the naive patients. In each group, 12 patients discontinued treatment; 4 patients in the DDI group and 7 patients in the non-DDI group because of adverse events. There were no AIDS-defining events in the antiretroviral-treated patients in both groups. 16 patients of the special combination group (DDI, D4T and EFV) were evaluated for more than 24 weeks. Suppression of HIV-1 RNA to <50 copies /mL were found in 75% of the naive and 43% of the pretreated patients. No relevant mutations were found during treatment.CONCLUSION:The new formulation of Didanosin as a once-a-day capsula in a protease sparing regimen was well-tolerated, effective in reducing viral load and in preventing AIDS-defining events. The combination of DDI, D4T and EFV proved to be a potent therapy without developing relevant mutations.