J.-M. Molina

High rate of virologic suppression with raltegravir plus etravirine and darunavir/ritonavir among treatment-experienced patients infected with multidrug-resistant HIV: results of the ANRS 139 TRIO trial.

BACKGROUND The introduction of 2 or 3 fully active drugs in human immunodeficiency virus (HIV)-infected patients receiving failing antiretroviral therapy is a key determinant of subsequent treatment efficacy. The aim of this study was to assess the safety and efficacy of a regimen containing raltegravir, etravirine, and darunavir/ritonavir for treatment-experienced patients infected with multidrug-resistant HIV. METHODS Patients enrolled in this phase II, noncomparative, multicenter trial were naive to the investigational drugs and had plasma HIV RNA levels >1000 copies/mL, a history of virologic failure while receiving nonnucleoside reverse-transcriptase inhibitors (NNRTI), > or =3 primary protease inhibitor and nucleoside reverse transcriptase inhibitor (NRTI) mutations, and < or =3 darunavir and NNRTI mutations. The primary end point was the proportion of patients with plasma HIV RNA levels <50 copies/mL at 24 weeks. RESULTS A total of 103 patients enrolled in the study. At baseline, genotypic resistance profiles showed a median of 4 primary protease inhibitor mutations, 1 NNRTI mutation, and 6 NRTI mutations. In addition to the investigational drugs, 90 patients (87%) received optimized background therapy that included NRTIs (86 patients) or enfuvirtide (12 patients). At week 24, 90% of patients (95% confidence interval, 85%-96%) had an HIV RNA level <50 copies/mL. At week 48, 86% (95% confidence interval, 80%-93%) had an HIV RNA level <50 copies/mL. The median CD4 cell count increase was 108 cells/mm(3). Grade 3 or 4 clinical adverse events were reported in 15 patients (14.6%). Only 1 patient discontinued the investigational antiretroviral regimen, because of an adverse event. CONCLUSION In patients infected with multidrug-resistant virus who have few remaining treatment options, the combination of raltegravir, etravirine, and darunavir/ritonavir is well tolerated and is associated with a rate of virologic suppression similar to that expected in treatment-naive patients.

Effects of Recombinant Human Interleukin 7 on T-Cell Recovery and Thymic Output in HIV-Infected Patients Receiving Antiretroviral Therapy: Results of a Phase I/IIa Randomized, Placebo-Controlled, Multicenter Study

Interleukin 7 induces a well-tolerated, dose-dependent, and sustained increase of CD4 T cells in human immunodeficiency virus-infected individuals treated with antiretroviral therapy, through an expansion of peripheral T cells that do not express activation markers, and increases thymic output in some patients.

Occurrence of Pneumocystis jiroveci pneumonia after allogeneic stem cell transplantation: a 6-year retrospective study

Summary:Pneumocystis jiroveci pneumonia (PCP) has become a rare opportunistic infection due to the efficacy of prophylactic regimens. We conducted a 6-year retrospective study at our institution. A total of 13 cases of PCP were diagnosed among 519 patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) (2.5%). In three patients, PCP occurred within the first 5 months following HSCT. These severely immunocompromised patients were receiving prophylaxis and had concomitant aspergillosis that caused rapid death in two of them. In 10 other patients, PCP occurred a median of 14.5 months after HSCT. In all these patients, PCP prophylaxis had been discontinued, mainly because of the suspected bone-marrow toxicity of the prophylactic regimen. Median CD4+ T cell count was 131/μl at diagnosis. Seven of these 10 patients were receiving immunosuppressive therapy for chronic graft versus host disease and three had a relapse of their hematological malignancy. One patient died from PCP despite high doses of cotrimoxazole. We conclude that PCP is still occurring after allogeneic HSCT, mainly as a late complication in patients in whom PCP prophylaxis had been prematurely discontinued. Long-term PCP prophylaxis should be maintained in patients receiving immunosuppressive drugs, and in those with low CD4+ T cell counts or a relapse of their hematological malignancy.

Breakthrough invasive fungal disease in patients receiving posaconazole primary prophylaxis: a 4-year study

Posaconazole (PSC) is currently recommended as primary prophylaxis in neutropenic patients with acute myeloid leukaemia (AML) and in allogenic haematopoietic stem cell transplantation (AHSCT) recipients with graft-versus-host disease (GVHD). Studies focusing on breakthrough invasive fungal disease (IFD) upon PSC prophylaxis show disparate results. In order to evaluate the incidence of IFD in patients on PSC prophylaxis and identify IFD risk factors, we carried out a retrospective study of all consecutive patients on PP from January 2007 to December 2010 in our hospital. Breakthrough IFDs were identified from the database of the central pharmacy and the French administrative database (PMSI), registering final medical diagnoses of hospitalized patients. Medical data were reviewed to study proven or probable IFD, according to EORTC/MSG definition. PSC plasma concentrations (PPC) were also retrieved. Poisson models were used for statistical analysis. Two hundred and seventy-nine patients received PSC prophylaxis for a median duration of 1.4 months (range 0.2-17.9). Proven (n=6) or probable (n=3) IFDs were diagnosed in nine cases (3.2%). IFD incidence rate per 100 person-month was 1.65 (95% CI, 0.79-2.97). IFDs were candidaemia (Candida glabrata, n=2), pulmonary invasive aspergillosis (n=3), disseminated fusariosis (n=2) and pulmonary mucormycosis (n=2). Seven deaths were reported, directly related to IFD in three patients (33.3%). First dosage of PPC under 0.3 mg/L was the single significant risk factor for IFD (RR, 7.77; 95% CI, 1.30-46.5; p 0.025). Breakthrough IFD in patients receiving PSC prophylaxis is rare but associated with a poor outcome. Low PSC plasma concentrations are associated with an increased risk of IFD.

Isosporiasis in patients with HIV infection in the highly active antiretroviral therapy era in France.

Isosporiasis, a rare cause of diarrhoea among HIV‐infected patients in the pre‐highly active antiretroviral therapy (HAART) era, seems to be re‐emerging.

Hepatosplenic candidiasis in the era of new antifungal drugs: a study in Paris 2000-2007

We report a retrospective study of 24 patients with haematological malignancy and hepatosplenic candidiasis. Clinical and biological features were similar to previous reports. No patient previously received antifungal prophylaxis. Liver or spleen histological examination revealed yeasts in 6/24 patients (25%) on direct examination but all cultures were negative. After a median duration of 7 months, antifungal treatment was discontinued in 58% of the patients with no relapse. Eleven (46%) patients died during follow up. After multivariate analysis, independent factors associated with death were the duration of neutropenia (p 0.022) and relapsing haematological malignancy (p 0.015).

Trichoderma fungaemia in a neutropenic patient with pulmonary cancer and human immunodeficiency virus infection

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Pharmacokinetic Study of Raltegravir in HIV-Infected Patients With End-Stage Liver Disease: The LIVERAL-ANRS 148 Study

BACKGROUND The end-stage LIVER disease and RALtegravir-Agence Nationale de Recherche sur le Sida et les hépatites (LIVERAL-ANRS) 148 study aimed to evaluate the safety, efficacy, and pharmacokinetic parameters of raltegravir (RAL) in human immunodeficiency virus (HIV)-infected patients with end-stage liver disease (ESLD) (substudy 1) and to assess the lack of pharmacokinetic interaction between RAL and the immunosuppressive regimen introduced after liver transplant (substudy 2). METHODS All patients received 400 mg RAL twice daily plus 2 nucleoside reverse transcriptase inhibitors. Liver function and immunovirological parameters were monitored throughout the study. Serial blood samples were drawn to explore RAL pharmacokinetics. Plasma concentrations of protein unbound, total RAL, and RAL glucuronide were determined by liquid chromatography-tandem mass spectrometry. RESULTS Ten patients with ESLD were analyzed in substudy 1. Despite an increased RAL exposure, RAL was well tolerated in all patients and no patient had to stop RAL therapy because of adverse events. Four patients were analyzed in substudy 2. No pharmacokinetic interaction was observed between cyclosporine, mycophenolic acid, and RAL. RAL tolerability was excellent; there were no episodes of acute rejection or opportunistic infection. HIV-RNA levels remained controlled and CD4 cell counts remained stable in all patients throughout the study. CONCLUSIONS The results of the substudy 1 support RAL administration to patients with ESLD. Substudy 2 assesses the safety, tolerability, and efficacy of RAL therapy in HIV-infected patients after liver transplant. RAL might be recommended as a suitable antiretroviral therapy in HIV-infected patients undergoing liver transplant.

Polylactic acid vs. polyacrylamide hydrogel for treatment of facial lipoatrophy: a randomized controlled trial [Agence Nationale de Recherches sur le SIDA et les Hépatites Virales (ANRS) 132 SMILE]

The aim of the study was to demonstrate the noninferiority of polyacrylamide hydrogel (PH) vs. polylactic acid (PLA) for the treatment of facial lipoatrophy in HIV‐infected adults.

Prevalence and clinical predictors of pulmonary tuberculosis among isolated inpatients: a prospective study

Guidelines help to prevent the transmission of Mycobacterium tuberculosis in healthcare settings, but may also result in the unnecessary isolation of many patients. We performed a prospective study to assess the prevalence and identify clinical predictors of culture-proven tuberculosis among inpatients isolated for suspected pulmonary tuberculosis (PTB) at our hospital. We also wished to validate a pre-existing clinical decision rule to improve our isolation policy. From August 2005 to January 2007, 134 patients isolated on admission to the ward for suspicion of PTB were prospectively enrolled. The admitting team made the decision to isolate patients on the basis of clinical and radiological findings, without the use of the clinical decision rule, and graded the overall suspicion of PTB. Twenty-six of the 134 isolated patients had PTB (prevalence: 19.4%), as well as one patient not isolated at admission. Univariate analysis revealed that PTB was significantly associated with young age, lack of human immunodeficiency virus (HIV) infection, weight loss, night sweats, fever, upper lobe disease and, especially, cavitary lesions on chest X-ray (adjusted OR 25.4, p <0.0001). Low suspicion of PTB by the admitting team and low clinical decision rule score had negative predictive values of 98.5% and 95.8% for PTB, respectively. Use of the clinical decision rule in addition to the team assessment would have led to the isolation of the patient with PTB not isolated on admission, and avoided 16 (14.8%) unnecessary isolations. In conclusion, the prevalence of PTB among isolated inpatients was high, and the use of a clinical decision rule in addition to clinical impression might improve isolation decisions.