First year of pre-exposure prophylaxis implementation in France with daily or on-demand tenofovir disoproxil fumarate/emtricitabine.

BACKGROUND: In January 2016, the French Medicine Agency initiated a Temporary Recommendation for Use (TRU) to allow the use of oral intake of tenofovir disoproxil fumarate and emtricitabine for pre-exposure prophylaxis (PrEP) in adults at high risk of HIV. We report the results of the first year of PrEP implementation in France. METHODS: Data were collected by physicians using a secured web subject-monitoring interface, with two forms: an initiation form, with patients' baseline characteristics, and an HIV seroconversion form. Univariate and adjusted multivariate analysis using a logistic regression model were performed to identify baseline factors associated with on-demand PrEP regimen prescription. RESULTS: From 4 January 2016 to 28 February 2017, 3405 subjects were enrolled, with 2774 initiation forms completed; 98.1% were male and 96.9% were MSM. An on-demand regimen was prescribed to 57% of subjects. Older age (OR for participants older than 50 years = 1.76, 95% CI 1.35-2.3, P < 0.001) and site of prescription (OR of former IPERGAY sites = 2.28, 95% CI 1.84-2.83, P < 0.001) were associated with on-demand prescription. Those reporting sexually transmitted infection (STI) and condomless anal sex with at least two different partners were less likely to receive on-demand PrEP (OR = 0.68, 95% CI 0.57-0.82 and 0.75, 95% CI 0.57-0.98, respectively; P < 0.05 for all). Four breakthrough HIV infections were reported during the study, in the context of PrEP interruption or acute infection at the time of PrEP initiation. CONCLUSIONS: In a real-life setting in France, PrEP was used, either daily or on-demand, mostly by MSM, with breakthrough infections being rare.

Daily cannabis and reduced risk of steatosis in human immunodeficiency virus and hepatitis C virus-co-infected patients (ANRS CO13-HEPAVIH).

Liver steatosis is common in human immunodeficiency virus (HIV)-hepatitis C virus (HCV)-co-infected patients. Some recent studies have found that cannabis use is negatively associated with insulin resistance in the general population and in HIV-HCV-co-infected patients. Given the causal link between insulin resistance and steatosis, we hypothesized that cannabis use has a positive impact on steatosis. Therefore, we aimed to study whether cannabis use in this population was associated with a reduced risk of steatosis, measured by ultrasound examination. ANRS CO13-HEPAVIH is a French nationwide multicentre cohort of HIV-HCV-co-infected patients. Medical and socio-behavioural data from clinical follow-up visits and annual self-administered questionnaires were prospectively collected. A cross-sectional analysis was conducted using data from the first visit where both ultrasound examination data for steatosis (positive or negative diagnosis) and data on cannabis use were available. A logistic regression model was used to evaluate the association between cannabis use and steatosis. Among study sample patients (n = 838), 40.1% had steatosis. Fourteen per cent reported daily cannabis use, 11.7% regular use and 74.7% no use or occasional use ("never or sometimes"). Daily cannabis use was independently associated with a reduced prevalence of steatosis (adjusted odds ratio [95% CI] = 0.64 [0.42;0.99]; P = .046), after adjusting for body mass index, hazardous alcohol consumption and current or lifetime use of lamivudine/zidovudine. Daily cannabis use may be a protective factor against steatosis in HIV-HCV-co-infected patients. These findings confirm the need for a clinical evaluation of cannabis-based pharmacotherapies in this population. Eudract.ema.europa.eu number, DGS050367.

Efficacy, safety and patient-reported outcomes of ledipasvir/sofosbuvir in NS3/4A protease inhibitor-experienced individuals with hepatitis C virus genotype 1 and HIV coinfection with and without cirrhosis (ANRS HC31 SOFTRIH study).

OBJECTIVES: Studies evaluating the efficacy and safety of the fixed-dose combination ledipasvir (LDV)/sofosbuvir (SOF) in patients coinfected with HIV-1 and hepatitis C virus (HCV) have mainly included treatment-naïve patients without cirrhosis. We aimed to evaluate the efficacy and safety of this combination in treatment-experienced patients with and without cirrhosis. METHODS: We conducted a multicentre, open-label, double-arm, nonrandomized study in patients coinfected with HIV-1 and HCV genotype 1 with and without cirrhosis, who had good viral suppression on their antiretroviral regimens. All patients were pretreated with a first-generation NS3/4A protease inhibitor (PI) plus pegylated interferon/ribavirin. Patients received a fixed-dose combination of LDV/SOF for 12 weeks, or for 24 weeks if cirrhosis was present. The primary endpoint was a sustained virological response (SVR) 12 weeks after the end of therapy. Secondary endpoints included safety, pharmacokinetics and patient-reported outcomes. RESULTS: Of the 68 patients enrolled, 39.7% had cirrhosis. Sixty-five patients [95.6%; 95% confidence interval (CI): 87.6-99.1%; P < 0.0001] achieved an SVR, with similar rates of SVR in those with and without cirrhosis. Tolerance was satisfactory, with mainly grade 1 or 2 adverse events. Among patient-reported outcomes, only fatigue significantly decreased at the end of treatment compared with baseline [odds ratio (OR): 0.36; 95% CI: 0.14-0.96; P = 0.04]. Mean tenofovir area under the plasma concentration-time curve (AUC) at week 4 was high, with mean ± SD AUC variation between baseline and week 4 higher in cirrhotic than in noncirrhotic patients (3261.57 ± 1920.47 ng/mL vs. 1576.15 ± 911.97 ng/mL, respectively; P = 0.03). Mild proteinuria (54.4%), hypophosphataemia (50.0%), blood bicarbonate decrease (29.4%) and hypokalaemia (13.2%) were reported. The serum creatinine level was not modified. CONCLUSIONS: LDV/SOF provided a high SVR rate in PI-experienced subjects coinfected with HCV genotype 1 and HIV-1, including patients with cirrhosis.

[Environmental radiation exposure of a thyroid cancer patient resulting from adjuvant iodine radiotherapy]. / Narazenie radiacyjne otoczenia chorego na raka tarczycy w wyniku uzupelniajacego leczenia jodem promieniotwórczym.

The aim of the study was to evaluate radiation risk in the environment of patients treated with 131I as an ablative therapy following radical surgery for the differentiated thyroid cancer. The activities of radioiodine used in this form of therapy approximate 2.8 GBq (76 mCi) and the in cases of the cancer metastases to other organs may be as high as 7.4 GBq (200 mCi). Dose equivalent rates were estimated in nine seated patients at the level of the thyroid close to the gland surface, and 0.5 and 1 m away from it. The measurements were performed at one, 24, 48, 72, 96, 120, 144, and 168 hours after the injection of 131I. The dose equivalent rates at various distances from the thyroid surface at different times were approximated with the exponential function by the least square method. Then, the dose equivalents were calculated from the moment of 131I application to the moment of the total removal of the isotope from the organism. From this relation, time intervals after which the annual threshold doses of 1, 5, and 50 mSv would be exceeded were computed as the function of the applied 131I activity. The results of the present study indicate that attendants of the patients treated with 131I will not be exposed to the doses of ionising radiation exceeding the acceptable annual thresholds provided with the limited time intervals. In addition, the present results may be useful in elaborating procedures of dealing with and handling the patients during their stay at hospital, at home, and at work.

[Intestinal parasites in four Warsaw kindergarten children in 1994-1996]. / Wystepowanie pasozytów jelitowych u dzieci w czterech przedszkolach warszawskich w latach 1994-1996.

In 1994/96 there were examined 588 children attending four Warsaw's kindergartens. Investigations were made by means of a standard coprological methods and by ELISA method for the presence of coproantigens of Giardia. The extensiveness of the infection was about 12.5%. It seems that now only oxyuriosis is the most important epidemiological problem among these children. The complexity of diagnosis and treatment of infected children and some health's education may improve their health and prevent the spreading of invasion.

Transport of lanthanides in milk into suckling rats.

The aim of this paper was to examine the transport of lanthanides in milk of contaminated rats into their sucklings and the retention of lanthanides in the sucklings. The research involved 55 female Wistar rats contaminated in the period of lactation and their offspring (400 infant rats). The study showed that in the period of lactation the transport in milk from the mother to the offspring of the lanthanide radionuclides under examination (144Ce, 147Nd, 152Sm, 155Eu and 160Tb) increased with their mass numbers: CE < Nd < Sm < Eu < Tb, and varied from 0.01% for 144Ce to 17.7% for 160Tb of the administered dose per litter. It was demonstrated that lanthanides were not absorbed from the digestive tract of sucklings because they were not detected beyond its area. Because of its highest concentration in milk 160Tb was chosen for further investigation of the kinetics of transport in individual segments of the digestive tract. The model for determining the function of lanthanide retention in separate parts of the digestive tract of sucklings and the half life of effective accumulation and elimination of 160Tb in the whole organism as well as in individual segments of the digestive tract are presented. Terbium-160 accumulation in sucklings increased whereas its elimination decreased with the age of the infant. No significant differences in 160Tb specific activity in stomach, and small and large intestines were observed in sucklings one to 21 days old. Biological half lives for retention of the contaminated milk were as follow: 0.25 +/- 0.021 per day for the stomach, 0.92 +/- 0.12 per day for the small intestine and 5.03 +/- 0.22 per day for the large intestine. The data obtained can be used in the evaluation of the doses absorbed from 160Tb and from other lanthanide radionuclides that are nonabsorbable from the digestive tract, as well as in estimation of the radiation risk to the offspring of mothers contaminated in the period of lactation.

Pharmacokinetics of amikacin in gamma-irradiated mice.

Concentrations of amikacin in sera, investigated 24 h after irradiation with 9 Gy gamma-rays of mice, were monitored using TDX system (Abbott), based on the fluorescence polarization immunoassay. Pharmacokinetic parameters of disposition (distribution + elimination) of the drug were calculated from the obtained data. In irradiated mice fast and slow phases of amikacin disposition were noted. In contrary, in the non irradiated mice only one-fast phase of the drug disposition was observed. The dependence of the disposition parameters of the antibiotic to the postirradiation tubular dystrophia and vascular changes was discussed.

The effect of toxic doses of lanthanum and cerium on the placental barrier and the blood/organ barrier in mice after intravenous injection of these elements.

In earlier studies the toxicity of the lanthanides was determined on the basis of the LD50/30 value, increase of serum ornithine carbamoyltransferase activity, and the degree of passage of the lanthanides to the fetuses and milk. The purpose of the present work was to investigate the effects of toxic doses of lanthanum and cerium on the function of the placental barrier and the blood/organ barrier in mice using substances of known molecular weight labelled with radionuclides (14C-aminoisobutyric acid--AIB, 3H-thymidine and 125I-albumin). Increased uptake of 14C-AIB and 3H-thymidine was demonstrated in the liver, spleen and placenta of mice after toxic doses of La and Ce indicating disturbances in the function of the blood/organ barrier (liver, spleen, placenta) due to damage to the vascular endothelium or cell membranes. No disturbances were shown in the function of the placental barrier (which would have caused increased passage of these markers to the fetus), and rupture of the cell membranes in the studied tissues was not demonstrated (it would have caused increased passage of 125I-albumin, a macromolecular compound) in any of the studied organs in mice.

Estimation of I131 doses absorbed by the thyroid in the period from May to June 1986.

In a randomly selected group of subjects the uptake of iodine radioisotopes was measured over the thyroid in the period May 6-23, 1986. From the obtained results the doses were estimated which were absorbed from April 28, 1986 until the time of complete disappearance of I131 from the thyroid. The highest dose of radiation absorbed from I131 by the thyroid was found in the youngest group (children aged 5 to 12 years) and it was 227.8 mGy (about 23 rads).

The metabolism of 4-iodantipyrine--I125 (RIAP) in rat organism after intravenous injection.

Radioactive antipyrine labelled with I125 (RIAP) is used in radioisotope diagnostic methods for determination of the total water content of the organism, and cerebral and cardiac blood flow. The purpose of this study was to investigate RIAP metabolism in rats after intravenous administration. The distribution, excretion and passage with milk to the newborn animals were studied. Electrophoresis of the urine of the rats treated with this radioisotope was done as well. A rapid accumulation of the radioisotope in the thyroid was observed (the T 1/2 value was about 4 hours, and the greatest accumulation of RIAP was after 15 hours). The biological time of RIAP elimination from the thyroid was 5 days. I125 concentration in other organs was below 1% of the injected dose. Excretion was mainly with urine in three phases. In the urine of the rats two I125-containing fractions were found (a iodide fraction and an unidentified fraction). RIAP administration to lactating females caused passage of between 10 and 20% of the administered dose to pass to the newborns with milk. RIAP administration to pregnant rats raised this proportion by several per cent. Thyroid blockade with potassium iodide had no effect on RIAP passage with milk to the newborns. These results suggest a rapid loss of iodine from RIAP after intravenous injection.