[Pre-exposure prophylaxis in HIV--a vision or soon a reality?]. / Präexpositionsprophylaxe bei HIV - Vision oder bald Realität?

Condom use is propagated as the most efficient measure to prevent HIV-transmission. For several reasons, condoms are NOT ALWAYS used or misapplied during sexual intercourse. Therefore, alternative preventive measures through intake of antiretroviral drugs before sexual intercourse with a (presumably) HIV-positive person are being considered, so called Pre-Exposure Prophylaxis (PrEP). In animal models the efficacy of HIV-PrEP was shown for Tenofovir alone or in combination with Emtricitabine). Several clinical studies are currently being conducted in different HIV-risk groups on various continents. First results from these studies are anticipated for the year 2010. In case of proven efficacy for HIV-PrEP, our health system would face a large interdisciplinary challenge. It would be a difficult task to define the appropriate recipients. Measures would have to be taken to limit possible misuse of antiretroviral drugs, due to the negative consequences with development of resistance, adverse events and illegal trading. It is already evident that HIV-PrEP will not provide absolute protection, nor will it replace other preventive strategies. However, if used cautiously, HIV-PrEP might be established as a useful supplement in the prevention of HIV. Paramount questions from the fields of epidemiology, behavioural science, logistics, health politics and ethics should be answered in advance.

[Epidemiology of primary drug resistance in chronically HIV-infected patients in Nordrhein-Westfalen, Germany, 2001-2005]. / Epidemiologie der primären Medikamentenresistenz bei chronisch HIV-Infizierten in Nordrhein-Westfalen 2001-2005.

BACKGROUND AND OBJECTIVE: Primary HIV drug resistance, characterized by mutant virus strains in untreated HIV-infected persons, is of significant epidemiological significance. Primary resistance is associated with reduced efficacy of antiretroviral therapy (ART). We determined the prevalence of primary resistance in Nordrhein-Westfalen, Germany. PATIENTS AND METHODS: Genotypic resistance testing was performed in a prospective multicenter study in chronically infected previously untreated HIV-positive patients before administration of first-line ART. Mutations were classified according to the International AIDS Society USA guidelines and the geno2pheno interpretation tool. RESULTS: Between January 2001 and December 2005, resistance testing was performed in 831 patients. 77.4% were males, the mean age was 39 years (SD: 10.5). The mean duration of diagnosis of HIV infection was 1.6 years (SD: 3.4). 32.4% of patients were at CDC stage C, mean CD4 cell count was 236 /microl (SD: 205), and mean viral load was 206,855 copies/ml (SD: 450,610). In total, resistance-associated mutations were detected in 75 patients (9.0%; 95%CI, 7.1-11.0). After inclusion of mutations E44D and V118I, resistance was identified in 99 patients (11.9%; 95%CI, 9.7-14.1). 5.4% had mutations indicating nucleoside reverse transcriptase inhibitor (NRTI) resistance (95%CI, 3.9-7.0), 3.0% had non-NRTI resistance (95%CI, 1.8-4.2), and 2.4% had protease inhibitor resistance (95%CI, 1.4-3.4), respectively. Two-class resistance was detected in 0.8% (95%CI, 0.2-1.5), three-class resistance in 0.5% (95%CI, 0.01-1.0). Mutations indicating revertant variants of resistant strains were found in 3.9% (95%CI, 2.5-5.2). Considering the variables age, gender, time since diagnosis, CDC stage, CD4 cell count, viral load, HIV subtype, ethnic origin, and HIV transmission group, no significant risk factor for the presence of primary resistance was demonstrated in univariate and mutlivariate analyses. CONCLUSION: The prevalence of primary resistant virus strains was about 10% in chronically infected ART-naive HIV-patients in the largest federal state of Germany. The majority of these patients had NRTI-associated resistance. No risk factor for the presence of primary drug resistance was identified. Because of the high prevalence and the possible impact on efficacy of drug treatment, routine genotypic resistance testing should be performed in untreated HIV-positive patients before administration of first-line ART.

[Passive prophylactic immunisation against post-transfusion hepatitis by immunoglobulin preparations: a prospective clinical study]. / Passive Immunprophylaxe der Posttransfusionshepatitis durch Immunglobulin-Präparationen. Eine prospektive klinische Studie.

In the course of a randomised prospective study involving 98 patients who had undergone cardiac surgery, 51 patients were given 20 g human immunoglobulin i.v. over four months, 47 received merely blood transfusions, like all other patients, averaging 4.4 units per patient. Antibodies against HBs antigen or Hbc antigen were present in 20% of patients before operation. After operation (plus blood transfusions) antibodies against hepatitis-B virus were demonstrated in 43% of the control group but 94% of those treated with immunoglobulins. These antibodies persisted in the course of further immunoglobulin administrations, while they fell in the control group. Hepatitis-B infections occurred in ten patients of the control group, after 30-90 days; three of them developed acute hepatitis. In the group treated with immunoglobulins there were only two patients with an infection, one of whom developed hepatitis. Antibodies against cytomegalic virus increased in the control group but not in the treatment group. In both groups there was the same incidence of non-A-non-B hepatitis.

[Transfer factor (TF) treatment of patients with HBs-Ag-positive chronic active hepatitis. A prospective, controlled study (author's transl)]. / Transfer-Faktor (TF) Behandlung von Patienten mit HBS-Ag-positiver chronisch aktiver Hepatitis. Eine prospektive, kontrollierte Studie.

It is a clinically and experimentally well supported working hypothesis that infection with hepatitis B virus may result in chronic active hepatitis in patients with suspected immune deficiencies. On this basis, a pilot study was performed in order to evaluate the effect of "specific" transfer factor (TF) in the treatment of HBS-Ag-positive chronic active hepatitis. From the leukocytes of 500 ml venous blood each of 40 volunteers that had completely recovered from acute virus hepatitis B within the last 6 months, a unique TF pool (40 units of TF) was prepared according to the method of Lawrence. Preexaminations indicated that this preparation was able to enhance cellular immune reactions in vitro. Thirteen patients with HBS-antigenemia and chronic active hepatitis (i.e., two liver biopsies within the last 6 or more months with the histological criteria of chronic aggressive hepatitis according to de Groote, elevated serum levels of bilirubin, alkaline phosphatase, transaminase activities, and/or gamma-globulines) were randomized: Seven received s.c. injections of two units of TF each on days 1 and 15, the other six saline. Conversion of skin reactions to some ubiquitous antigens occurred in the TF group, but no significant and constant drop of HBS-Ag serum titers was observed. Although some of the biochemical parameters seemed to ameliorate in the TF group, the differences versus the control group did not prove to be significant within the limited number of patients under observation. The in vitro reactivity of patients' lymphocytes to HBS-Ag, tested by means of the 3H-thymidine uptake, was never found enhanced after TF application. In the used doses, "specific" TF was not effective in the treatment of HBS-Ag-positive chronic active hepatitis; unfavorable side-effects were not observed.

Controlled clinical studies with an antidote against the urotoxicity of oxazaphosphorines: preliminary results.

A randomized study in 20 patients with cancer was carried out to test the clinical efficacy of sodium-2-mercaptoethane sulfonate (ASTA D-7093; mesnum) as an agent to prevent urotoxic side effects (in particular, hemorrhagic cystitis) during cytostatic therapy with the oxazaphosphorines cyclophosphamide and ifosfamide. Eleven patients received mesnum iv and nine patients received a standard prophylaxis. The frequency of microhematuria was significantly lower in the patients receiving mesnum. A slight microhematuria was observed in one patient. With the standard prophylaxis, all nine patients receiving single-agent therapy with ifosfamide or cyclophosphamide had hematuria and three of these had macrohematuria. According to the available results, a daily mesnum dose of 60% (wt/wt) of the ifosfamide or cyclophosphamide dose is recommended. This dose should be divided into three equal fractions. The first administration should be given concurrently with the cytostatic agent and the subsequent two administrations at 4 and 8 hours after administration of the cytostatic agent. Significantly higher doses of mesnum (eg, 133% of the cyclophosphamide or ifosfamide doses) lead to gastrointestinal disorders, which are easily reversible.

The fate of injected human IgG in the mouse liver: Uptake, immunological inactivation, and lysosomal reactions.

1. Human IgG is stored in the form of remarkable droplets in the cytoplasm of mouse hepatocytes following intravenous injection. 2. The earliest protein uptake occurs within 1 minute after injection and droplets can be found up to 32 hours thereafter; 64 hours p.i. the foreign protein is no longer visible in hepatocytes. 3. Electron microscopy reveals that the uptake occurs by a process of "macropinocytosis". The resulting protein droplets fuse with primary lysosomes and are transformed into phagolysosomes. 4. At the same time as the phagolysosomes are formed the IgG-droplets loose their immunological activity--as early as 2 hours after injection.