Increased risk of IRIS-associated tuberculosis in HIV-infected patients receiving Integrase Inhibitors.

BACKGROUND: Tuberculosis is associated with a risk of immune reconstitution inflammatory syndrome (IRIS) after ART initiation. METHODS: Data from all patients with newly diagnosed tuberculosis disease and uncontrolled HIV infection from 1997 to 2017 in a French center were retrospectively collected. We evaluated the incidence of tuberculosis-IRIS in patients initiating ART with or without integrase inhibitors (INSTI) RESULTS: Fifty-five patients were included: 21 receiving an INSTI regimen and 34 a non-INSTI regimen. Except with regard to ART regimen, the two groups were comparable (median CD4 of 85/mm3). The overall percentage of IRIS was 34% (19/55), with 52% IRIS in INSTI regimen and 23% in non-INSTI regimen respectively (P=0.04). In a multivariate logistic model, we observed an increased risk of IRIS in the INSTI regimen compared to the non-INSTI, with an OR at 3.33 [95% CI, 1.01-11.1] (P=0.05) CONCLUSIONS: ART containing integrase inhibitors could be associated with increased incidence of TB-associated IRIS.

Infectious complications in HIV-infected kidney transplant recipients.

Renal transplantation is now a viable alternative for dialysis in HIV-infected patients who achieve good immunovirological control with current antiretroviral therapy regimens available. However, there are few studies that analyze the incidence of post-transplant infections in this population. In this study, a retrospective analysis of data files of 24 HIV-infected kidney transplant (KT) recipients was undertaken, matched to 21 non-infected controls. All patients received induction with anti-interleukin-2 antibodies and were followed in the Pitié-Salpêtrière Hospital in Paris, France. The rate of incidence of post-transplant infections was 23.58 and 26.98/100 patient-years, in HIV-infected and HIV-negative groups (relative risk [RR]: 0.90; 95% confidence interval [CI]: 0.58-1.39; p = 0.63). In HIV-infected KT recipients, bacterial infections were the most frequent (67.7%), followed by viral (14.7%) and fungal and parasitic infections (8.8%). Similar trends were seen in the control group. Incidence of opportunistic infections was similar in HIV-infected KT recipients and controls (38.2 vs. 26.5%; p = 0.44). There were three post-transplant HIV reactivations in two patients, secondary to poor adherence to medication. HIV status did not influence survival, but infections increased the risk of unfavorable outcome. Incidence of post-transplant infections was similar in HIV-infected KT recipients and controls. Infections, but not HIV status, had adverse effects on patient and graft survival.

Darunavir/ritonavir monotherapy at a low dose (600/100 mg/day) in HIV-1-infected individuals with suppressed HIV viraemia.

Background: Darunavir/ritonavir is a potent PI with a high genetic barrier and pharmacological robustness favourably investigated as monotherapy. Whether darunavir could be dose reduced in the context of monotherapy deserves investigation. Methods: Patients with HIV suppressed viraemia (plasma viral load <50 copies/mL for 12 months) under ART who had switched to darunavir/ritonavir monotherapy at 600/100 mg/day between 2013 and 2015 were included in this observational 48 week single-centre study. The primary outcome was the proportion of patients with virological success (defined as plasma viral load <50 copies/mL) at week 24. Secondary outcomes included treatment strategy success and resistance. Results: Thirty-one patients were included with the following baseline characteristics [median (IQR)]: age 52 years (47-57), CD4+ 649 cells/mm3 (463-813), ART duration 16.3 years (9.2-22.3), nadir CD4+ 195 cells/mm3 (144-261) and duration of HIV suppression 7.8 years (4.8-9.7). Prior to switch, ART consisted of PI monotherapy for 28 of 31 patients [darunavir/ritonavir 800/100 mg/day (n = 26), lopinavir/ritonavir (n = 1) and atazanavir/ritonavir (n = 1)] and a triple drug regimen for 3 of 31 patients. Within the 48 weeks of follow-up, no virological failure occurred and two patients discontinued 600/100 mg of darunavir/ritonavir due to side effects at week 16 and 40, leading to a virological suppression rate of 100% (95% CI = 89-100) at weeks 24 and 48. Strategy success rates were 96.8% (95% CI = 83.3-99.9) at week 24 and 93.5% (95% CI = 78.6-99.2) at week 48. Median (IQR) Ctrough values of 800/100 mg of darunavir/ritonavir and 600/100 mg of darunavir/ritonavir were 1537 ng/mL (1286-1724) and 1255 ng/mL (873-2161), respectively. Conclusions: A lower dose of darunavir/ritonavir used as monotherapy (600/100 mg/day) was highly effective in virologically suppressed HIV-infected patients. Further studies are needed to confirm these data.

Changes in eosinophil count during bacterial infection: revisiting an old marker to assess the efficacy of antimicrobial therapy.

INTRODUCTION: Eosinopenia as a criterion of sepsis has been the subject of debate for decades. Different authors have proposed different cut-off values. METHODS: A prospective study was conducted from February to August 2016. Hospitalized adults suffering from a bacterial infection with eosinopenia, defined as an eosinophil count <100/mm3, were included. Patients were divided into two groups according to the first day of effective antimicrobial therapy. They were observed for 5days in order to evaluate whether recovery from eosinopenia was predictive of an appropriate antibiotic regimen. RESULTS: One hundred and twenty-two patients were screened and 96 were included. Group 1 patients (n=70) received effective antimicrobial therapy from day 0. Their eosinophil count increased significantly between day 0 and day 1 (p<0.0001). Group 2 patients (n=26) received delayed effective antimicrobial therapy, and there was no significant difference in eosinophil count between day 0 and day 1 (p=0.55). Moreover, eosinophil counts normalized on day 5 in both groups. The mean duration of antimicrobial therapy was comparable in the two groups (7.7±1.16 days). The antibiotics most often prescribed in both groups were intravenous cephalosporins. During follow-up, all patients were considered to be cured after day 30. CONCLUSIONS: The eosinophil count appears to normalize faster than C-reactive protein (CRP) and polymorphonuclear neutrophils in eosinopenic patients on appropriate antimicrobial therapy. This simple test is easy to perform as part of a regular complete blood count, with no additional costs as required for CRP or procalcitonin.

Rapid plasma viral suppression in naive HIV-infected patients with high CD4 cells and low viraemia initiating a dual nucleoside reverse transcriptase inhibitor strategy: a proof-of-concept study.

OBJECTIVES: To evaluate whether a dual nucleoside reverse transcriptase inhibitor (NRTI) strategy can control HIV replication in antiviral therapy (ART)-naive HIV-infected patients with a high CD4 cell count and a low viral load (VL). METHODS: This observational study included all HIV-infected treatment-naive patients with a CD4 cell count >300 cells/mm(3), a plasma HIV RNA between 1000 copies/mL and 30,000 copies/mL and wild-type virus who initiated dual NRTI ART between January 2008 and December 2012. HIV RNA and CD4 cell count were assessed at Day 0, Week (W) 4, W12, W24 and W48. The primary endpoint was the proportion of patients with a plasma VL (pVL) <50 copies/mL at W24. RESULTS: Twenty patients were included. The median (IQR) baseline characteristics were: time since HIV diagnosis, 25 months (8-66 months); CD4 cell count, 592 cells/mm(3) (405-798 cells/mm(3)); HIV RNA, 10,395 copies/mL (4106-16,566 copies/mL); and HIV DNA, 464 copies/10(6) peripheral blood mononuclear cells (195-1168 copies/10(6) PBMC). Nineteen patients received tenofovir/emtricitabine and one patient received abacavir/lamivudine. At W12, 88% of the patients with available data (n = 16/18, 95% CI 0.65-0.99) had a pVL <50 copies/mL. Overall, the proportion of patients with a pVL <50 copies/mL was 100% (n = 20/20, 95% CI 0.83-1.0) at W24 and 95% (n = 18/19, 95% CI 0.74-0.99) at W48 (with one patient lost to follow-up and one patient with poor treatment compliance). The median increase in CD4 cells was 83 cells/mm(3) (40-310 cells/mm(3)). There was no discontinuation of antiretroviral therapy for any reason such as lack of efficacy or toxicity. CONCLUSIONS: This pilot study suggests that, in patients with a high CD4 cell count and a low VL, a dual NRTI strategy may represent a potentially effective treatment strategy to control HIV replication. This needs to be confirmed in larger controlled clinical studies.

Real-time sonoelastography in the diagnosis of prostate cancer.

AIMS: Sonoelastography (SEG) is a noninvasive ultrasound (US) method able to differentiate tissues according to their stiffness. Our objective was to establish whether transrectal (TR) SEG may improve prostate cancer detection, alone or associated with other US methods. PATIENTS AND METHODS: We analyzed the data of 65 patients, mean age 68 years (49 - 81 years), examined March 2009-September 2010. The patients had at least one of the following malignancy suspicion criteria: PSA > 4 ng /ml (minimum 2 determinations), nodule(s) at digital rectal examination (DRE +) or previous gray scale TRUS positive appearance. All patients underwent TRUS, Doppler-US and SEG in the same session, followed by systematic prostate biopsies (6-12 cores). Histopathology and imaging findings were correlated. RESULTS: Twenty-eight out of 65 patients (43%) were diagnosed with prostate cancer. Overall, SEG had a sensitivity of 67.85%, specificity 62.16%, positive predictive value 57.57% and negative predictive value 71.85%. However, SEG diagnostic reliability appeared to be higher for subgroups of patients having PSA >10 ng / ml, lower number of fragments collected by PBP (6 vs. 10-12 cores) and age > 70 years. CONCLUSION: SEG appears to be useful in the diagnosis of prostate cancer as it may increase the diagnosis accuracy in specific target groups.

Value of ultrasound elastography in the diagnosis and management of prostate carcinoma.

The aim of the paper is to review and illustrate the role of sonoelastography in the diagnostic and therapeutic approach of prostate cancer. The examination technique and normal appearance are presented. The paper describes and illustrates the appearance of prostate cancer and suggested diagnostic scores. Artifacts, causes for false results and limitations are discussed and also illustrated. The diagnostic influence of intraprostatic tumor location, tumor volume and Gleason score are presented. The paper also reviews the statistical diagnostic value of the method, the relation to prostate biopsy and magnetic resonance assessment. In the end, potential uses and future developments of the method are mentioned.