Recovery of long-term natural protection against reactivation of CMV retinitis in AIDS patients responding to highly active antiretroviral therapy.

OBJECTIVES: To see whether in severely immunosuppressed AIDS patients (with prior Cytomegalovirus retinal disease) who have significant increases in CD4+ lymphocytes following the initiation of highly active antiretroviral therapy (HAART) anti-Cytomegalovirus (CMV) maintenance therapy can be withdrawn with no subsequent progression of CMV retinitis. METHODS: Eight patients with AIDS and one or more previous episodes of CMV retinitis interrupted anti-CMV maintenance therapy following the successful beginning of HAART. CD4 cell counts and HIV-RNA were monitored monthly while measurement of CMV antigenemia and ophthalmoscopy were carried every 2 weeks thereafter. RESULTS: The HAART recipients in whom anti-CMV maintenance therapy had been interrupted had measureable increases of CD4+ T lymphocytes, substantial control of both HIV-RNA and CMV viraemia and did not show recurrence of retinitis during a mean follow-up of 98.4 weeks (range 78-120, SD 15.2). CONCLUSIONS: Anti-CMV maintenance therapy can be interrupted with no subsequent progression of retinal damage over a long time in patients with AIDS who successfully respond to HAART with a significant increase in CD4 cell count.

Twice-weekly dapsone for primary prophylaxis against Pneumocystis carinii pneumonia in HIV-1 infection: efficacy, safety and pharmacokinetic data.

OBJECTIVES: In this study we evaluated the pharmacokinetics, efficacy and safety of dapsone given 100 mg twice weekly as primary prophylaxis against Pneumocystis carinii pneumonia (PCP) in patients with HIV-1 infection. METHODS: This was a prospective open trial, evaluating a total of 55 HIV-1-infected patients with CD4 cell counts below 200/mm3 and without previous episodes of PCP. Plasma concentrations of dapsone were determined with high-performance liquid chromatography (HPLC). After a mean follow-up of 471 days, the PCP rates per year of observation were 6.79%. Discontinuation of treatment as a result of severe side effects was required in four patients (7.5%). At steady state, mean plasma concentrations 24, 72, 96 and 144 h following the administration of dapsone were 1.46plus minus0.8, 0.28plus minus0.20, 0.30plus minus0.21 and 0.37plus minus0.27 mg/L, respectively. Dapsone plasma levels showed a high interpatient variability. The values for the pharmacokinetic parameters were comparable to those described for healthy volunteers. CONCLUSIONS: The administration of 100 mg twice weekly of dapsone seems appropriate to maintain effective plasma concentrations of the drug and to prevent PCP with good safety in patients with HIV-1-related immunodeficiency.

Stability of cefodizime in solution and compatibility with other injectable drugs.

The stability of cefodizime in five intravenous infusion fluids (0.9% sodium chloride, 5% dextrose in water, 10% dextrose in water, 5% amino acid injection, 3% polygeline) was studied at room temperature and at 4 degrees C. The compatibility of cefodizime with commonly used injectable drugs (ranitidine, metoclopramide, folinic acid, furosemide, aminophilline, 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 degrees 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 degrees 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.(ABSTRACT TRUNCATED AT 250 WORDS)

Risk of reactivation of tuberculosis in the course of human immunodeficiency virus infection.

OBJECTIVES: To establish, in a longitudinal study, whether reactivation of latent tuberculous infection takes place below an identifiable immunological threshold in subjects with human immunodeficiency virus (HIV) infection. METHODS: We followed up for 2 years 44 subjects with HIV infection who had a positive intradermal reaction to tuberculin. All subjects were asymptomatic at enrollment. End points of the study were the development of active tuberculosis or the final evaluation (24 months since the beginning) for those who did not develop tuberculosis over the study period. Total lymphocyte count, CD4+ lymphocyte count and beta-2 microglobulin serum levels were measured at baseline, during the period of observation (every 3-6 months) and at the end point. Multiple Antigen Skin Testing and purified protein derivative (PPD) testing were also performed at baseline and end point, as well as in intermediate phases of the study (every 6 and 12 months respectively). RESULTS: Ten subjects (22.7%) developed tuberculosis during the study period. Both baseline and end point values of the parameters investigated differed significantly between subjects who developed tuberculosis and those who did not. Cox's model showed that total and CD4+ lymphocyte counts as well as beta-2 microglobulin levels had a prognostic value at a univariate analysis; CD4+ and beta-2 microglobulin retained statistical significance in a multivariate evaluation. CD4+ lymphocyte count was the parameter most strongly associated with the development of tuberculosis. CONCLUSIONS: Tuberculosis in this setting most often reactivates only when immune surveillance has fallen to an identifiable level. Planners of antituberculous chemoprophylactic policies should consider the downgrading tendency of immune function in these subjects in order to choose the most appropriate time to intervene in the course of HIV infection. Starting prophylaxis in HIV-infected subjects only when CD4+ cells have dropped below the value of 500/mm3 seems to be a more fruitful option than the currently adopted strategy, which recommends time-limited (12 months) administration of daily isoniazid to all PPD+ HIV-infected subjects regardless their immunological status.

[Acute pneumonia and cell-mediated immunity in patients with HIV infection]. / Polmoniti acute e immunità cellulo-mediata in pazienti con infezione da HIV.

The aim of this retrospective study is to evaluate the correlation between T-cell immunity and pulmonary disorders in a group of Italian subjects with HIV infection. HIV-infected patients seen at the Institute of Infectious Diseases, University of Verona, were included in this study if they had a specific acute pneumonia, a CD4+ cell count and a CD4+/CD8+ ratio during the 60 days immediately before the onset of pulmonary disease. Cases receiving any antimicrobial prophylaxis were excluded. Pneumonia was recognized by usual clinical and radiologic abnormalities. The diagnostic procedure included sputum examination, bronchoscopy with bronchoalveolar lavage and transbronchial biopsy. The specimens were processed for bacterial, mycobacterial and fungal stains and cultures. Ziehl-Neelsen, periodic acid-Schiff and silver methenamine stains were performed on the transbronchial biopsy specimens in addition to usual pathologic examinations mononuclear. Determination of percentage of peripheral blood mononuclear cells bearing CD4+ and CD8+ markers was done by conventional fluorescent antibody cell-sorter analysis of the mononuclear cell population. Absolute number of CD4+ lymphocytes was determined by multiplying the total lymphocyte count by the percent of mononuclear cells bearing CD4+ marker. From October 1987 to August 1991, 61 patients, 50 males and 11 females, had 65 episodes of specific pneumonia. The average age of patients was 31.4 years (range 29-59 years). The risk factors for HIV infection included intravenous drug abuse (47 patients), homosexuality (6 patients), bisexuality (3 patients) and heterosexual contact (5 patients). Before the onset of pulmonary disorders, patients were classified in the following clinical HIV-related stages: asymptomatic state (22 episodes), ARC (22 episodes) and AIDS (21 episodes). In decreasing order of frequency diagnosis of pneumonias were PCP (29 episodes), community-acquired bacterial pneumonia (16 episodes), pulmonary tuberculosis (8 episodes), nonspecific interstitial pneumonia (4 episodes), PCP and pulmonary tuberculosis (3 episodes), cytomegalovirus pneumonia (2 episodes), and one of each episode of PCP and pulmonary cryptococcosis, pulmonary candidiasis, pulmonary Kaposi's sarcoma. The mean and the standard deviation of immunologic values regarding the four primary diagnostic groups were: PCP CD4+/CD8+ 0.50 +/- 0.42, CD4+/mm3 196 +/- 190; bacterial pneumonia CD4+/CD8+ 0.53 +/- 0.44, CD4+/mm3 247 +/- 139; pulmonary tuberculosis CD4+/CD8+ 0.62 +/- 0.38, CD4+/mm3 260 +/- 170; nonspecific interstitial pneumonia CD4+/CD8 + 0.57 +/- 0.48, CD4+/mm3 240 +/- 189. No significant statistical differences with respect to CD4+/CD8 ratios and CD4+ cell counts among these diagnostic groups were found by standard analysis of variance.(ABSTRACT TRUNCATED AT 400 WORDS)

[Chemotaxis deficiency in patients with HIV infection]. / Deficit della chemiotassi in pazienti con infezione da HIV.

Increased susceptibility to bacterial recurrent infection is characteristically associated with impaired B cells function but also with a defective PMN function. We studied PMN CT in 15 HIV positive drug addicts patients with persistent generalized lymphoadenopathy (PGL), in 15 symptom free HIV negative drug addicts (SFDA) and in 15 healthy blood donors to evaluate influence of HIV infection on PMN functions. CT of patients with PGL was reduced to 78% (p < 0.0001) and 75% (p < 0.00001) of CT in SFDA patients and healthy blood donors, respectively. We conclude that HIV infection causes defective PMNL CT and then it can increase susceptibility to bacterial recurrent infections in these patients.

Nosocomial epidemic of active tuberculosis among HIV-infected patients.

In an investigation of a nosocomial outbreak of tuberculosis, 18 HIV-infected inpatients were found to have been exposed to Mycobacterium tuberculosis; active tuberculosis developed in 8, 7 within 60 days of diagnosis of the index case. The patients with lower total lymphocyte and CD4 lymphocyte counts were more likely to get the disease than were those with higher counts. A low score on multiple antigen skin testing was also associated with the development of active tuberculosis. 4 of the 18 patients had a positive tuberculin skin test before exposure to M tuberculosis; none of them subsequently got the disease.

[Cutaneous leishmaniasis: an autochtonous case in Switzerland?]. / Kutane Leishmaniose: autochthoner Fall in der Schweiz

Different kinds of Phlebotomus, which are responsible for the infectiousness of cutaneous leishmaniasis, have been identified at different places in Europe. The pathogenic agent, Leishmania tropica, essentially linked to climatic circumstances, seems slowly to gain ground north of the Mediterranean Sea. The chance of having an autochthonous case in Ticino (Southern Switzerland) is existing. A treatment with Rifampicin has been successful.