Successful treatment of disseminated Acanthamoeba sp. infection with miltefosine.

We report on an HIV-negative but immunocompromised patient with disseminated acanthamoebiasis, granulomatous, amoebic encephalitis and underlying miliary tuberculosis and tuberculous meningitis. The patient responded favorably to treatment with miltefosine, an alkylphosphocholine. The patient remained well with no signs of infection 2 years after treatment cessation.

Granulomatous amoebic encephalitis caused by Acanthamoeba amoebae of genotype T2 in a human immunodeficiency virus-negative patient.

Acanthamoeba amoebae of genotype T2 were identified as the causative agent of Acanthamoeba skin lesions and granulomatous amoebic encephalitis (GAE) in a human immunodeficiency virus-negative patient with underlying tuberculosis. To our knowledge this, is the first case of GAE involving genotype T2.

Efficacy and safety of TMC114/ritonavir in treatment-experienced HIV patients: 24-week results of POWER 1.

BACKGROUND: The ongoing phase IIb POWER 1 (TMC114-C213) trial is designed to assess efficacy and safety of the protease inhibitor (PI) TMC114 (darunavir) in treatment-experienced HIV-1-infected patients. DESIGN: This randomized, partially blinded, 24-week dose-finding study compared efficacy and safety of four doses of TMC114 plus low-dose ritonavir (TMC114/r) with investigator-selected control PI(s) (CPI[s]). METHODS: Patients with one or more primary PI mutation and HIV RNA > 1000 copies/ml received optimized background therapy, plus TMC114/r 400/100 mg once daily, 800/100 mg once daily, 400/100 mg twice daily or 600/100 mg twice daily, or CPI(s). The primary endpoint (intent-to-treat) compared proportions of patients achieving viral load reduction >or= 1.0 log10 copies/ml from baseline. RESULTS: In total, 318 patients were treated. Baseline mean viral load was 4.48 log10 copies/ml; median CD4 cell count was 179 cells/microl. In the CPI arm 62% of patients discontinued (virological failure: 54%); 10% of TMC114/r patients discontinued. More TMC114/r (69-77%) than CPI patients (25%) reached the primary endpoint (P < 0.001); 43-53% of TMC114/r patients and 18% of the CPI arm achieved viral load < 50 copies/ml (P < 0.001). TMC114/r demonstrated greater mean CD4 cell count increases versus CPI(s) (68-124 versus 20 cells/microl; P < 0.05). TMC114/r 600/100 mg twice daily demonstrated the highest virological and immunological responses. Adverse event incidence was similar between treatments; headache and diarrhoea were more common with CPI(s). CONCLUSIONS: TMC114/r demonstrated statistically higher 24-week virological response rates and CD4 cell count increases than CPI(s). TMC114/r 600/100 mg twice daily has received regulatory approval in treatment-experienced patients.

Antiviral activity of the neutralizing antibodies 2F5 and 2G12 in asymptomatic HIV-1-infected humans: a phase I evaluation.

BACKGROUND: The human monoclonal antibodies (MAbs) 2F5 and 2G12 were identified to be two of the most potent neutralizing antibodies against HIV-1. In a first human study they have been shown to be safe after repeated intravenous infusions to asymptomatic HIV-1-infected individuals. However, the antiviral effects of antibody treatment have not been fully analyzed in this first clinical trial. METHODS: The aim of the present study was to gain a preliminary insight into the antiviral effects of 2F5 and 2G12 in humans. For this purpose, plasma samples obtained from the previous phase I study were studied for RNA copy numbers by reverse transcriptase-polymerase chain reaction. As a measure for activation of complement levels of the major complement factor C3 were measured by enzyme-linked immunosorbent assay. Flow cytometry was used to study T-lymphocyte counts and the amount of infected peripheral blood mononuclear cells (PBMC) was determined by co-culture with uninfected donor PBMC. Virus escape from antibody neutralization was determined in vitro in a PBMC neutralization assay. RESULTS: Transient reduction in viral loads was observed in five of seven patients. Vigorous complement activation was observed directly after HIV-specific antibody infusions. The number of infective peripheral blood mononuclear cells was reduced in some patients whereas CD4+ T-lymphocyte counts and CD4+/CD8+ ratios were transiently increased in all patients. Virus escape occurred only against 2G12. CONCLUSIONS: Analysis of disease progression markers indicate that antibody therapy may have antiviral effects. These findings suggest that neutralizing antibodies should be further evaluated as an alternative therapeutic approach in HIV-1 disease.

A phase I trial with two human monoclonal antibodies (hMAb 2F5, 2G12) against HIV-1.

OBJECTIVE: To study the safety, immunogenicity and pharmacokinetics of two intravenously administered human monoclonal antibodies (hMAb 2F5, 2G12) against HIV-1 in humans. DESIGN: Open label clinical phase I trial. SETTING: Primary institutional care. PATIENTS: Seven HIV-1-infected healthy volunteers with > or = 500 x 10(6)CD4 cells/l and < or = 10,000 HIV-1 RNA copies/ml, not treated with highly active antiretroviral therapy (HAART), entered and finished the study. INTERVENTIONS: and main outcome measures: Eight separate infusions of the hMAb were administered over a 4-week period (total dose 14 g). The safety was assessed by physical examination, blood chemistry, complete blood cell count and recording adverse events. 2F5 and 2G12 plasma levels were determined prior to and at the end of each infusion and during the follow-up period of 22 weeks. RESULTS: No clinical or laboratory abnormalities were observed throughout the study. The median distribution half-life (t(1/2 alpha)) of 2F5 and 2G12 was 1.02 (range, 0.77-1.47) days and 2.49 (range, 0.92-4.59) days, respectively. The elimination half-life (t(1/2 beta)) was calculated to be 7.94 (range, 3.46-8.31) days for 2F5 and 16.48 (range, 12.84-24.85) days for 2G12. The median plasma concentration immediately after the first infusion was 216 microg/ml (range, 158-409 microg/ml) for 2F5 and 238 microg/ml (range, 197-402 microg/ml) for 2G12. Multiple infusions resulted in maximum plasma concentrations of 374 microg/ml (range, 304-700 microg/ml) and 605 microg/ml (range, 479-897 microg/ml) for 2F5 and 2G12, respectively. CONCLUSIONS: This study showed that the hMAb 2F5 and 2G12 are safe and well tolerated by HIV-1-infected subjects.

Absence of human immunodeficiency virus infection after intentional injection of infected blood.

We report the case of a young man who injected himself intravenously with 2 mL of human immunodeficiency virus (HIV)-infected blood and failed to develop HIV infection.

A prospective, randomized, double-blind multicenter comparison of parenteral ertapenem and ceftriaxone for the treatment of hospitalized adults with community-acquired pneumonia.

BACKGROUND: Ertapenem is a once-daily parenteral beta-lactam licensed in the United States in November 2001 and in Europe in May 2002. OBJECTIVE: This study compared the efficacy and safety profiles of ertapenem with those of ceftriaxone for the treatment of hospitalized adult patients with serious community-acquired pneumonia (CAP) requiring parenteral therapy. METHODS: In this prospective, double-blind (with sponsor blinding), multicenter study, adult patients with CAP were stratified by Pneumonia Severity Index (< or = 3 or > 3) and age (< or = 65 or > 65 years) and randomized (2:1) to receive IV or intramuscular (IM) ertapenem 1 g once daily or IV or IM ceftriaxone 1 g once daily. Investigators could switch patients to an oral antimicrobial agent if clinical improvement was shown after at least 3 days of parenteral therapy. RESULTS: A total of 364 patients were randomized to treatment: 239 to the ertapenem group and 125 to the ceftriaxone group. Three patients in the ertapenem group and 2 in the ceftriaxone group did not receive study therapy. Of the treated patients, 77.1% (182/236) of patients in the ertapenem group and 75.6% (93/123) in the ceftriaxone group were clinically evaluable. Among clinically evaluable patients, the mean (SD) durations of parenteral and total (parenteral plus optional oral) therapy were 5.5 (2.6) and 11.5 (2.7) days for ertapenem and 5.6 (2.8) and 11.7 (3.0) days for ceftriaxone, respectively. Streptococcus pneumoniae was the most frequently isolated pathogen in both treatment groups. Cure rates were 92.2% for clinically evaluable patients in the ertapenem group and 93.6% for those in the ceftriaxone group (95% CI for the difference, adjusted for stratum, -8.6 to 5.7), fulfilling the criteria for statistical equivalence. At completion of parenteral therapy, 94.7% of patients in the ertapenem group and 95.8% in the ceftriaxone group showed clinical improvement. Infused vein complications (ertapenem, 3.4% [8/236]; ceftriaxone, 7.3% [9/123]) and elevated transaminase levels (ertapenem, 6.3% [13/207]; ceftriaxone, 7.1% [8/113]) were the most common adverse events in both groups. CONCLUSIONS: In this study of hospitalized adult patients, ertapenem therapy, with an oral switch option, was as effective as ceftriaxone with the same oral switch option for treatment of CAP requiring initial parenteral therapy. The overall safety profiles of the 2 drugs were comparable.

[Bronchial asthmatic disease associated with tobacco dust--an occupational lung disease?]. / Tabakassoziiertes Asthma--eine Berufskrankheit?

Hypersensitivity to allergens in tobacco leaf as a cause of occupational asthma in workers of the tobacco manufacturing industry has been reported previously. We describe the case of a female employee working in a tobacco plant with asthmatic symptoms occurring at the working place. The symptoms described by the patient and the strong correlation to periods at work is highly suggestive for an occupational disease. The diagnosis of occupational bronchial asthma is supported by a positive skin test and bronchial provocation test with tobacco dust.

The role of antiretroviral therapy in the incidence of pancreatitis in HIV-positive individuals in the EuroSIDA study.

AIM: This study investigated the incidence of pancreatitis and its association with antiretroviral therapy (ART), focussing on stavudine and didanosine. METHODS: EuroSIDA has collected information on pancreatitis since Summer 2001. All identified cases have been verified by the coordinating centre. Individuals were followed from June 2001 or the date of entry into EuroSIDA (whichever occurred later) until a diagnosis of pancreatitis or the last study visit. Factors associated with pancreatitis were investigated using Poisson regression. Cumulative lengths of exposure to didanosine without stavudine, stavudine without didanosine, stavudine with didanosine, and other ART were time-updated variables. Treatment variables were fitted with a 6-month time lag. RESULTS: There were 43 (nine presumptive) pancreatic events in 9678 individuals during 33 742 person-years (incidence 1.27/1000 person-years). The incidence among those with no, 2 or less and over 2 years' exposure to ART including stavudine and didanosine was 1.24, 1.73 and 0.78/1000 person-years, respectively. In multivariable analysis, higher baseline CD4 cell counts were associated with a decreased risk of pancreatitis. There was no evidence of an association of pancreatitis with cumulative exposure to didanosine and stavudine, didanosine without stavudine, stavudine without didanosine, or other ART. CONCLUSION: We observed a low overall rate of pancreatitis in the years 2001-2006, and did not find an association of an increased incidence of pancreatitis with cumulative exposure to antiretroviral agents generally, and to didanosine and stavudine in particular.

Factors associated with the development of opportunistic infections in HIV-1-infected adults with high CD4+ cell counts: a EuroSIDA study.

BACKGROUND: Limited data exist on factors predicting the development of opportunistic infections (OIs) at higher-than-expected CD4(+) cell counts in human immunodeficiency virus (HIV) type 1-infected adults. METHODS: Multivariate Poisson regression models were used to determine factors related to the development of groups of OIs above their respective traditional upper CD4(+) cell count thresholds: group 1 (>or=100 cells/ microL), OIs caused by cytomegalovirus, Mycobacterium avium complex, and Toxoplasma gondii; group 2 (>or=200 cells/ microL), Pneumocystis pneumonia and esophageal candidiasis; and group 3 (>or=300 cells/ microL), pulmonary and extrapulmonary tuberculosis. RESULTS: In groups 1, 2, and 3, 71 of 9,219, 125 of 7,934, and 36 of 7,838 patients, respectively, developed >or=1 intragroup OI. The strongest predictor of an OI in groups 1 and 2 was current CD4(+) cell count (for group 1, incidence rate ratio [IRR] per 50% lower CD4(+) cell count, 5.37 [95% confidence interval {CI}, 3.71-7.77]; for group 2, 4.28 [95% CI, 2.98-6.14]). Injection drug use but not current CD4(+) cell count predicted risk in group 3. Use of antiretroviral treatment was associated with a lower incidence of OIs in all groups, likely by reducing HIV-1 RNA levels (IRR per 1-log(10) copies/mL higher HIV-1 RNA levels for group 1, 1.50 [95% CI, 1.15-1.95]; for group 2, 1.68 [95% CI, 1.40-2.02]; and for group 3, 1.89 [95% CI, 1.40-2.54]). CONCLUSION: Although the absolute incidence is low, the current CD4(+) cell count and HIV-1 RNA level are strong predictors of most OIs in patients with high CD4(+) cell counts.

Ertapenem versus ceftriaxone for the treatment of community-acquired pneumonia in adults: combined analysis of two multicentre randomized, double-blind studies.

The efficacy and safety of ertapenem, 1 g once a day, for the treatment of community-acquired pneumonia (CAP) requiring parenteral therapy were compared with those of ceftriaxone, 1 g once a day, in 866 hospitalized adults randomized in two prospective, double-blind, multicentre studies. Patients were stratified according to Pneumonia Severity Index (< or = 3 or >3) or age (< or = 65 or >65 years). After > or = 3 days of parenteral antimicrobial therapy, patients who had clinically improved could be switched to oral co-amoxiclav. The median durations of parenteral, oral and total therapy in the 658 clinically evaluable patients, of whom 88% were switched to oral therapy, were 4, 7 and 12 days, respectively, in both treatment groups. The most common pathogen was Streptococcus pneumoniae, of which 79% (143/181) were penicillin susceptible and 3.3% (6/181; three in each treatment group) were penicillin resistant. Cure rates for the two treatments were equivalent: 91.9% for ertapenem and 92.0% for ceftriaxone (95% confidence interval for the difference, adjusted for strata: -4.5 to 4.4). Cure rates in the different severity and age strata and bacterial eradication rates for both treatment groups were also similar. The most common drug-related adverse events in both treatment groups were diarrhoea and mild-to-moderate elevations in aminotransferase levels. The results of these studies demonstrate that ertapenem, 1 g once a day, was highly effective therapy for CAP in hospitalized adults with moderate-to-severe disease.