Antimony to Cure Visceral Leishmaniasis Unresponsive to Liposomal Amphotericin B.

We report on 4 patients (1 immunocompetent, 3 immunosuppressed) in whom visceral leishmaniasis had become unresponsive to (or had relapsed after) treatment with appropriate doses of liposomal amphotericin B. Under close follow-up, full courses of pentavalent antimony were administered without life-threatening adverse events and resulted in rapid and sustained clinical and parasitological cure.

Pharmacokinetic-pharmacodynamic modeling of unboosted Atazanavir in a cohort of stable HIV-infected patients.

Limited data on the pharmacokinetics and pharmacodynamics (PK/PD) of unboosted atazanavir (uATV) in treatment-experienced patients are available. The aim of this work was to study the PK/PD of unboosted atazanavir in a cohort of HIV-infected patients. Data were available for 58 HIV-infected patients (69 uATV-based regimens). Atazanavir concentrations were analyzed by using a population approach, and the relationship between atazanavir PK and clinical outcome was examined using logistic regression. The final PK model was a linear one-compartment model with a mixture absorption model to account for two subgroups of absorbers. The mean (interindividual variability) of population PK parameters were as follows: clearance, 13.4 liters/h (40.7%), volume of distribution, 71.1 liters (29.7%), and fraction of regular absorbers, 0.49. Seven subjects experienced virological failure after switch to uATV. All of them were identified as low absorbers in the PK modeling. The absorption rate constant (0.38 ± 0.20 versus 0.75 ± 0.28 h(-1); P = 0.002) and ATV exposure (area under the concentration-time curve from 0 to 24 h [AUC(0-24)], 10.3 ± 2.1 versus 22.4 ± 11.2 mg · h · liter(-1); P = 0.001) were significantly lower in patients with virological failure than in patients without failure. In the logistic regression analysis, both the absorption rate constant and ATV trough concentration significantly influenced the probability of virological failure. A significant relationship between ATV pharmacokinetics and virological response was observed in a cohort of HIV patients who were administered unboosted atazanavir. This study also suggests that twice-daily administration of uATV may optimize drug therapy.

First presentation for care of HIV-infected patients with low CD4 cell count in Lyon, France: risk factors and consequences for survival.

To identify the risk factors associated with presentation for care with CD4 cell count ≤ 200 cells/mm(3) and death in HIV-infected patients in Lyon, France. Data were analyzed on participants from mid-1992 to December 2006 in the Lyon section of the French Hospital Database on HIV Infection. Patients were stratified into two categories according to CD4 cell count at first presentation for care in University of Lyon hospitals: Group 1 (Gr1) patients with CD4 ≤ 200 cells/mm(3) and Group 2 (Gr2) patients with CD4 >200 cells/mm(3). Multivariate logistic regression assessed the risk factors associated with first presentation for care with CD4 ≤ 200 cells/mm(3). Survival was analyzed according to the Cox regression model. Among 3569 eligible patients (838 females and 2731 males, mean age: 36.3 ± 10.3 years), 1139 (31.9%) were categorized as Gr1. The factors associated with first presentation for care with CD4 ≤ 200 cells/mm(3) were: older age, male gender, route of HIV transmission, migrant populations, geographical areas other than Rhône-Alpes, and access to care in 1992-1997. Overall mortality was higher in Gr1 than in Gr2 (24.4% [278/1139] vs. 4.1% [101/2430]; p<0.001). The risk of death was 5.81 [4.61-7.32] in Gr1 compared to Gr2. In addition to CD4 cell count, age and enrollment periods for care were factors independently related to death. Despite public health efforts in Lyon, one-third of HIV-infected patients reach the health care system with CD4 cell count ≤ 200 cells/mm(3), which was linked with higher mortality.

Imported pulmonary histoplasmosis in three French cavers after a trip to Cuba.

Pulmonary histoplasmosis is a rare disease in France, where all cases are imported. Diagnosis is difficult in nonendemic areas, often based on travel history and observation of epidemic in a group. We report three cases of pulmonary histoplasmosis that occurred in a group of 12 French cavers traveling to Cuba.

T-cell response to superantigen restimulation during menstrual toxic shock syndrome.

Menstrual toxic shock syndrome (MTSS) is a severe toxin-mediated disease associated with Staphylococcus aureus producing toxic shock syndrome toxin 1 (TSST-1), a superantigen that mediates a potent activation of Vß-2 T cells. In animal models, superantigen treatment of responsive T cells induces their initial proliferation, followed by unresponsiveness upon further superantigen stimulation. To determine whether T cell unresponsiveness occurs in humans during the acute phase of MTSS, we collected T cells from a patient with MTSS and restimulated them ex vivo with recombinant TSST-1. The expansion of T cells collected during the acute phase of disease was compared with positive controls including basal-state T cells (collected 70 days after MTSS) restimulated with TSST-1, and T cells stimulated with enterotoxin B superantigen. We found that TSST-1-induced expansion of acute phase T cells was not inferior to that observed in positive controls. We conclude that T cells were still reactive to TSST-1 during the acute phase of MTSS in this patient. As the persistence of TSST-1 production could thus be associated with further expansion of TSST-1-reactive T cells and a rapid worsening of symptoms, this study adds further support to the need for immediate eradication of the focus of infection as soon as MTSS is suspected.

Effectiveness of antibiotics for acute sinusitis in real-life medical practice.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: Determining bacterial aetiology of acute sinusitis is difficult without employing invasive procedures. Most episodes of acute sinusitis resolve spontaneously. Antibiotics have demonstrated efficacy for the treatment of acute bacterial sinusitis in clinical trials yet little is known of their effectiveness in real-life treatment settings. WHAT THIS STUDY ADDS: Most cases of untreated acute sinusitis resolved spontaneously. Antibiotics were more effective when given within the first 10 days of treatment. This had no effect on later recurrence. Patients with poor oro-dental condition or recent antibiotic use may derive the most benefit from an antibiotic prescription and this should be considered by prescribers. The antibiotics used were found to be equally effective. Existing recommendations to identify acute sinusitis with high probability of bacterial origin, such as the French recommendations, fever or duration of symptoms fail to identify patients in whom antibiotics are more effective. AIMS: To assess the effectiveness of antibiotics in acute bacterial sinusitis. METHODS: This was a prospective cohort study with 2 months follow-up of 5640 patients with acute sinusitis included by a random sample from 1174 GPs and 120 ENT specialists. Main outcomes were short-term initial success, defined as the absence of prescription of (another) antibiotic or sinus lavage within 10 days, and lack of recurrence between the 11th and 60th day, after initial success. RESULTS: Initial success was found in 88.7% (95% CI 85.1, 91.4%) of patients without antibiotic prescription at inclusion and 96.2% (95% CI 95.7, 96.7%) of patients prescribed antibiotics. The 10 day adjusted hazard ratio (HR) for treatment failure (new antibiotic prescription or sinus drainage) with initial antibiotics compared with no antibiotics was 0.30 (95% CI 0.21, 0.42) with no difference between antibiotics. Antibiotics were more effective in patients with poor oro-dental condition (HR 0.04, 95% CI 0.01, 0.20) and in patients who had already used antibiotics during the previous 2 months (HR 0.09, 95% CI 0.03, 0.28). For patients without failure at 10 days, recurrence between the 11th and 60th day was similar whether or not they had initially been prescribed an antibiotic, 94.1% (95% CI 93.4, 94.7%) and 93.4% (95%CI 90.3, 95.5%), respectively. CONCLUSION: Most acute sinusitis cases not prescribed antibiotics resolve spontaneously. Antibiotics reduced by 3.3-fold the risk of failure within 10 days, without impact on later recurrence. The greatest benefit of antibiotics was found for patients with poor oro-dental condition or with antibiotic use within the previous 2 months.

Health-related quality of life in HIV-1-infected patients on HAART: a five-years longitudinal analysis accounting for dropout in the APROCO-COPILOTE cohort (ANRS CO-8).

BACKGROUND: The long-term efficacy of Highly Active Antiretroviral Therapies (HAART) has enlightened the crucial role of health-related quality of life (HRQL) among HIV-infected patients. However, any analysis of such extensive longitudinal data necessitates a suitable handling of dropout which may correlate with patients' health status. METHODS: We analysed the HRQL evolution over 5 years for 1,000 patients initiating a protease inhibitor (PI)-containing therapy, using MOS SF-36 physical (PCS) and mental (MCS) scores. In parallel with a classical separate random effects model, we used a joint parameter-dependent selection model to account for non-ignorable dropout. RESULTS: HRQL evolved according to a two-phase pattern, characterized by an initial improvement during the year following HAART initiation and a relative stabilization thereafter. Immunodepression and self-reported side effects were found to be negative predictors of both PCS and MCS scores. Hepatitis C virus coinfection and AIDS clinical stage were found to affect physical HRQL. Results were not significantly altered when accounting for dropout. CONCLUSION: Such results, obtained on a large sample of HIV-infected patients with extensive follow-up, underline the need for a regular monitoring of patients' immunological status and for a better management of their experience with hepatitis C and HAART.

Factors associated with nonadherence to highly active antiretroviral therapy: a 5-year follow-up analysis with correction for the bias induced by missing data in the treatment maintenance phase.

This study aimed to identify factors associated with nonadherence during the maintenance phase of highly active antiretroviral therapy (months 12-60) in the Anti PROtease Cohort (APROCO) cohort after correcting for the bias due to missing outcome data. A Heckman 2-stage approach (generalized estimating equations probit model) was used to compare visits with moderate or poor adherence and visits with high adherence. Between months 12 and 60, at least 1 self-reported adherence measure was available for 970 of the 1110 patients with at least 12 months of follow-up (3889 visits with adherence assessments). Adherence was rated as high at 2466 visits, moderate at 1125, and poor at 298. After adjustment for "missingness," moderate and poor adherence were independently associated with age (younger), perceived treatment side effects, dosing frequency different from twice daily, and a protease inhibitor-based regimen. They were also associated with depression and lack of support from the main partner. High adherence was most likely among patients born outside the European Union. A comparison restricted to poor-adherence and high-adherence visits yielded a similar pattern of predictors. Adjusting for missing outcome data changed the predictor set. Reasons for nonadherence are multifactorial. Psychosocial interventions and the selection of the best-tolerated regimens are needed to improve long-term adherence of HIV-infected patients to their lifelong treatment.

Secondary pulmonary syphilis: report of a likely case and literature review.

We report the case of a homosexual, HIV-positive man with typical secondary syphilis and multiple excavated pulmonary subpleural nodules. Syphilis with direct pulmonary involvement was suggested by a positive result of PCR of a bronchoalveolar lavage fluid specimen, then confirmed by a positive therapeutic test result. Only 9 reports of pulmonary involvement in secondary syphilis have been reported to date in the English-language literature. Clinicians should be aware of this atypical localization of syphilis.

Prevalence of toxoplasma encephalitis in AIDS patients treated with Didanosine hospitalised in a French infectious service.

In a previous work, we have showed in mice infected with an avirulent strain of Toxoplasma gondii and receiving a didanosine treatment, an important decrease of brain cysts. It is why, the purpose of this study was to investigate the effect of didanosine treatment on AIDS patients having developed Toxoplasma encephalitis. 60 patient reports were analyzed: 22 patients (group 1) did not received didanosine in their antiretroviral treatment and 38 (group 2) were treated with didanosine. The results showed that an antiretroviral therapy was prescribed for 93% of patients, 50% of them received only zidovudine and protease inhibitors were prescribed for 37%. The regimens given most frequently were those including zidovudine plus lamivudine or zidovudine plus indinavir. Among the group 1, 18% have had a relapse of Toxoplasma encephalitis. In the group 2, 37% of the patients suffered from one episode of TE while 16% have had two TE after the pause in their didanosine treatment, the maximum occurring between 4 and 24 months after the pause of didanosine. This study showed that didanosine seems to have an effect on cerebral cysts. Also, this work made a synthesis about the different treatment used in AIDS patients and the new molecules yet in development against T. gondii.

Value of preoperative investigations in diagnosing prosthetic joint infection: retrospective cohort study and literature review.

The diagnosis of a prosthetic joint infection is difficult, but crucial for appropriate treatment. Scintigraphy with specific markers for infection (labelled white cells or immunoglobulin-G) has been reported as a more reliable diagnostic tool than clinical assessment (fever, fistula), laboratory studies (polynuclear neutrophil count, erythrocyte rate sedimentation, and C-reactive protein), and preoperative aspiration. In the first part of this study, we retrospectively reviewed 230 patients admitted with a suspected prosthetic joint infection, and examined the validity of the different diagnostic tools for the group as a whole and for subgroups according to the Coventry classification. In the second part, we reviewed 35 articles about preoperative evaluation of infection in prosthetic joints and compared them to our findings. Our study indicates that C-reactive protein and joint aspiration are the most useful tools to diagnose prosthetic joint infection even in situations of chronic infection (Coventry type II).

Failure and success of HIV tests for the prevention of HIV-1 transmission by blood and tissue donations.

French blood banks recently implemented nucleic acid testing (NAT) of all blood donations to reduce the risk of HIV transmission during the pre-seroconversion period. For tissue donation, HIV infection screening relies on HIV p24 antigen and anti-HIV-1 and 2 antibody detection. In this report, two related cases of infectious donations are described from a cornea donor during the preseroconversion window who was infected by an HIV antibody and NAT negative blood donor. After investigation, the blood donor was found to be herself in the preseroconversion window. Two months after donation, she was found to be HIV positive. The residual risk of HIV infectious blood donations since NAT has been introduced is estimated to be lower than one out of 2.5 millions. Individual NAT instead of minipool testing would not increase significantly the blood transfusion safety. In contrast, introduction of NAT should be considered to increase tissue donation safety as soon as such screening will be possible technically.

Impact of a patient education program on adherence to HIV medication: a randomized clinical trial.

Patients' knowledge of their HIV condition and its treatment, which has been recognized as a factor that influences adherence to antiretroviral therapy, can be improved through educational programs. This prospective, randomized, controlled trial compared an experimental group that participated in an educational program and a control group with standard care. The study evaluated the impact of an educational intervention on adherence to antiretroviral therapy, patients' knowledge, quality of life, and therapeutic response in patients treated with highly active antiretroviral therapy. Three hundred twenty-six patients were analyzed at inclusion. A higher level of adherence was associated with patients who were older, had higher incomes, and did not smoke. CD4 cell count and plasma viral load were correlated with adherence at entry. The educational intervention had an impact on adherence and knowledge in the experimental group at 6 months, which was maintained at 12 and 18 months. A delayed increase in adherence was observed in the control group at 12 months. No significant impact on quality of life was observed over time. The patients' health status improved in 56% of the experimental group subjects and 50% of the control subjects. However, no significant impact was shown on CD4 cell count and plasma viral load. This study shows that an educational intervention improves adherence to antiretroviral regimens and health status and suggests that it should be initiated early in therapy.

Health-related quality of life after 1 year of highly active antiretroviral therapy.

OBJECTIVE: We investigated the impact of the first year of highly active antiretroviral therapy (HAART) on health-related quality of life (HRQL). METHODS: Medical data for patients in the French APROCO cohort were collected at enrollment (M0) and month 12 (M12). A self-administered questionnaire gathered information about HRQL (Medical Outcome Study 36-Item Short Form Health Survey) and toxicity-related symptoms. Using the twenty-fifth percentile of HRQL scales in the French population as a threshold, patients with normal values in at least three mental and three physical scales were considered to have a "normal HRQL." RESULTS. Of the 1053 patients followed through M12, HRQL data at M0 and M12 were available for 654. Among the 233 patients with a normal baseline HRQL, 63 (27.0%) experienced a deterioration of HRQL at M12. Among the 421 patients with a low baseline HRQL, 121 achieved a normal HRQL at M12. Logistic regression showed that factors independently associated with a normal HRQL at M12 were normal baseline HRQL, baseline CD4 count <500 cells/mm, time since HIV diagnosis <8 years, undetectable HIV-RNA at M12, and lower number of self-reported symptoms at M12. CONCLUSION: An assessment of HRQL should be integrated to efficacy outcomes to evaluate and compare long-term strategies properly and to optimize the durability of response to antiretroviral therapy.