Clinical epidemiology and survival of progressive multifocal leukoencephalopathy in the era of highly active antiretroviral therapy: Data from the Italian Registry Investigative Neuro AIDS (IRINA)

Human immunodeficiency virus (HIV)-associated progressive multifocal leukoencephalopathy (PML) remains a relevant clinical problem even in the era of highly active antiretroviral therapy (HAART). Aims of the study were to analyze clinical and treatment-related features and the survival probability of PML patients observed within the Italian Registry Investigative Neuro AIDS (IRINA) during a 29-month period of HAART. Intravenous drug use, the presence of focal signs, and the involvement of white matter at neuroradiology increased the risk of having PML. A reduced probability of PML was observed when meningeal signs were reported. Patients starting HAART at PML diagnosis and previously naïve for antiretrovirals showed significantly higher 1-year probability of survival (.58), compared to those continuing HAART (.24), or never receiving HAART (.00). Higher CD4 cell count were associated with a higher survival probability (.45). At multivariate analysis, a younger age, higher CD4, starting HAART at PML diagnosis, the absence of previous acquired immunodeficiency syndrome (AIDS)-defining events, and the absence of a severe neurologic impairment were all associated with a reduced hazard of death. The use of cidofovir showed a trend towards a reduced risk of death.     

West African Immigrants and New Patterns of Malaria Imported to North Eastern Italy

Background : With the settlement of increasing numbers of immigrants from tropical African countries into Italy over the last decade, the epidemiologic pattern of imported malaria underwent significant change. Italian immigrants originating from endemic areas who revisit their country of origin have exhibited an increasing incidence of malaria: the Italian Ministry of Health recorded an increase of from 14% in 1986 to 40.4% in 1991.
Methods : This retrospective study reviews the epidemiology of all malaria cases recorded from 1988 to 1991 in a regional reference center in North Eastern Italy. Epidemiologic factors, including the details of their travel experience, were examined for all cases, and the relation of immigrants to Italian-born citizens were compared.
Results : Of the 100 cases recorded during this period, 36 were diagnosed in 1988–1989 and 64 in 1990–1991. Immigrants accounted for six times more cases during the latter than during the former time period. Compared to nonimmune short-term travelers, immigrants experienced significantly milder forms of the disease and lower levels of parasitemia ( Plasmodium falciparum ) on admission. Notably, 10 cases of malaria in immigrants were not recognized at first observation on microbiology.
Conclusions : With the advent of this new risk group of immigrants that originate from endemic countries, especially those making occasional short visits to their native countries, this new epidemiologic profile of malaria imported into Italy shows the need for improvement in the areas of prophylaxis, pretravel education, and diagnostic services.     

Sorafenib Therapy for Hepatocellular Carcinoma in an HIV–HCV Coinfected Patient: A Case Report

Background/Aims.

HIV and hepatitis C virus (HCV) share common modes of transmission, resulting in about 33% incidence of coinfection among people infected with HIV. The survival benefit from highly effective antiretroviral therapy (HAART) for HIV infection is resulting in an increased incidence of hepatocellular carcinoma (HCC) in this population. There are no reports to date regarding the coadministration of HAART and sorafenib for hepatocellular carcinoma.

Methods.

We report the case of a 42-year-old male patient coinfected with HIV and HCV who developed advanced HCC not amenable to curative therapy. The patient was treated with sorafenib, an oral multikinase inhibitor shown to lead to a longer median survival time and time to progression in patients with advanced HCC. Antiretroviral therapy was continued during sorafenib therapy.

Results.

The patient achieved a partial tumor response after 3 months and continued to respond at subsequent assessments. His serum α-fetoprotein normalized from 2,172 IU/ml to 2 IU/ml. He had durable stable disease after 23 months of therapy. Antiretroviral therapy was efficacious (CD4⁺ lymphocyte count, 377/μl; HIV viremia, <50 copies/ml). The simultaneous administration of these therapies was well tolerated. No grade 3 or 4 toxicities were observed. Exacerbation of pre-existing hypertension, grade 2 diarrhea, and grade 1 skin reaction were observed.

Conclusions.

This is the first report in which sorafenib has been successfully used to treat HCC in a patient with HIV–HCV coinfection.     

Stability of Cefodizime in Solution and Compatibility with Other Injectable Drugs

Summary

The stability of cefodizime in five intravenous infusion fluids (0.9% sodium chloride, 5% dextrose in water, 1096 dextrose in water, 5% amino acid injection, 3% polygelinc) was studied at room temperature and at 4°C. The compatibility of cefodizime with commonly used injectable drugs (ranitidine, metoclopramide, folinic acid, furoscmide, aminophillinc, methylprednisolone, betamethasone, hydrocortisone, dexamethasone, ketoprofen, noramidopyrine, acetylcysteine, digoxin, diazepam, acetylsalicylic acid, chlorpromazine, clonidine, clomipramine) was studied in 0.9% sodium chloride and 5% dextrose at room temperature. At intervals during the storage periods (up to 24 hrs at room temperature; up to 6 days at 4°C) color, clarity and solution pH were examined; cefodizime content was determined by a microbiological method. Cefodizime concentrations remained greater than 90% of the initial concentrations in all infusion fluids for at least 24 hrs at room temperature and 6 days at 4°C. No visual changes or appreciable changes in pH were observed for any of the solutions. Immediate clouding was observed when chlorpromazine was combined with the solution of cefodizime. A color change was observed when acetylcysteine was mixed with cefodizime. An increase in pH was noted when aminophilline was added to the solution of cefodizime. However, cefodizime concentrations remained greater than 90% of the initial concentrations of the solutions after mixture with all the tested drugs for at least 24 hrs at room temperature. We conclude that, under the conditions of this study, cefodizime sodium 4 mg/ml is stable for at least 24 hours at room temperature and for at least 6 days at 4°C in all infusion fluids tested, and that numerous injectable agents did not affect cefodizime concentrations when admixed in 0.9% sodium chloride or 5% dextrose in water for 24 hours at room temperature.     

Clinical epidemiology and survival of progressive multifocal leukoencephalopathy in the era of highly active antiretroviral therapy: data from the Italian Registry Investigative Neuro AIDS (IRINA)

Human immunodeficiency virus (HIV)-associated progressive multifocal leukoencephalopathy (PML) remains a relevant clinical problem even in the era of highly active antiretroviral therapy (HAART). Aims of the study were to analyze clinical and treatment-related features and the survival probability of PML patients observed within the Italian Registry Investigative Neuro AIDS (IRINA) during a 29-month period of HAART. Intravenous drug use, the presence of focal signs, and the involvement of white matter at neuroradiology increased the risk of having PML. A reduced probability of PML was observed when meningeal signs were reported. Patients starting HAART at PML diagnosis and previously na?ve for antiretrovirals showed significantly higher 1-year probability of survival (.58), compared to those continuing HAART (.24), or never receiving HAART (.00). Higher CD4 cell count were associated with a higher survival probability (.45). At multivariate analysis, a younger age, higher CD4, starting HAART at PML diagnosis, the absence of previous acquired immunodeficiency syndrome (AIDS)-defining events, and the absence of a severe neurologic impairment were all associated with a reduced hazard of death. The use of cidofovir showed a trend towards a reduced risk of death.