Patients’ high acceptability of a future therapeutic HIV vaccine in France: a French paradox?

International audienc

Evaluating patient preference and satisfaction for human immunodeficiency virus therapy in France

Objectives The objectives were 1) to elicit relative preferences for attributes of antiretroviral therapies (ART) in people living with HIV (PLWH) and 2) to explore satisfaction and adherence with current ART. Patients and methods We conducted a multicenter cross-sectional study, consecutively enrolling PLWH receiving an ART. The quantitative part estimated the strength of preference for different attributes using an online discrete choice experiment (DCE). DCE data were analyzed using a mixed logit regression model. Qualitative data were collected through individual interviews. A preliminary coding framework was developed which was then further refined and applied during thematic analysis of factors influencing satisfaction and adherence. Results A total of 101 PLWH took part in the quantitative part and 31 in the qualitative part. Over 90% had an undetectable viral load. Quantitative data revealed a strong preference for a treatment with limited drug–drug interactions, diarrhea and long-term health problems (P<0.0001), and that did not need to be taken on an empty stomach (P<0.0001). Patients also preferred to avoid problems associated with treatment failure (P<0.0001) or one that left them with a higher viral load after the first weeks of treatment (P=0.044). Differences in CD4 cell count, and pills that must be taken with food were not significant drivers of treatment choice. The strength of these attributes was reflected in the qualitative data, highlighting the importance patients place on treatment efficacy, and also suggesting that some of these attributes may impact adherence. Many factors influencing adherence and satisfaction with treatment were identified, including pill size, worry about sexual transmission and impact on social life. Conclusion Most of the attributes included in this survey were important to participants when choosing an ART, in particular those related to quality of life, and these should be taken into account in order to optimize adherence and satisfaction

Modeling the evolution of the neutralizing antibody response against SARS-CoV-2 variants after several administrations of Bnt162b2

Because SARS-CoV-2 constantly mutates to escape from the immune response, there is a reduction of neutralizing capacity of antibodies initially targeting the historical strain against emerging Variants of Concerns (VoC)s. That is why the measure of the protection conferred by vaccination cannot solely rely on the antibody levels, but also requires to measure their neutralization capacity. Here we used a mathematical model to follow the humoral response in 26 individuals that received up to three vaccination doses of Bnt162b2 vaccine, and for whom both anti-S IgG and neutralisation capacity was measured longitudinally against all main VoCs. Our model could identify two independent mechanisms that led to a marked increase in humoral response over the successive vaccination doses. In addition to the already known increase in IgG levels after each dose, we identified that the neutralization capacity was significantly increased after the third vaccine administration against all VoCs, despite large inter-individual variability. Consequently, the model projects that the mean duration of detectable neutralizing capacity against non-Omicron VoC is between 366 days (Beta variant, 95% Prediction Intervals PI [323; 366]) and 606 days (Alpha variant, 95% PI [555; 638]). Despite a very low protection after three doses, the mean duration of detectable neutralizing capacity against Omicron variants varies between 184 days (BA.5 variant, 95% PI [155; 215]) and 268 days (BA.1 variant, 95% PI [238; 302]). Our model shows the benefit of incorporating the neutralization capacity in the follow-up of patients to better inform on their level of protection against the different SARS-CoV-2 variants as well as their optimal timing of vaccine administration

A prospective, observational study of fidaxomicin use for Clostridioides difficile infection in France.

To describe the characteristics, management and outcomes of hospitalised patients with Clostridioides difficile infection (CDI) treated with and without fidaxomicin. This prospective, multicentre, observational study (DAFNE) enrolled hospitalised patients with CDI, including 294 patients treated with fidaxomicin (outcomes recorded over a 3-month period) and 150 patients treated with other CDI therapies during three 1-month periods. The primary endpoint was baseline and CDI characteristics of fidaxomicin-treated patients. At baseline, the fidaxomicin-treated population included immunocompromised patients (39.1%) and patients with severe (59.2%) and recurrent (36.4%) CDI. Fidaxomicin was associated with a high rate of clinical cure (92.2%) and low CDI recurrence (16.3% within 3 months). Clinical cure rates were ≥90% in patients aged ≥65 years, those receiving concomitant antibiotics and those with prior or severe CDI. There were 121/296 (40.9%) patients with adverse events (AEs), 5.4% with fidaxomicin-related AEs and 1.0% with serious fidaxomicin-related AEs. No fidaxomicin-related deaths were reported. Fidaxomicin is an effective and well-tolerated CDI treatment in a real-world setting in France, which included patients at high risk of adverse outcomes.Trial registration: Description of the use of fidaxomicin in hospitalised patients with documented Clostridium difficile infection and the management of these patients (DAFNE), NCT02214771, www.ClinicalTrials.gov

Resistance of Omicron subvariants BA.2.75.2, BA.4.6 and BQ.1.1 to neutralizing antibodies

Convergent evolution of SARS-CoV-2 Omicron BA.2, BA.4 and BA.5 lineages has led to the emergence of several new subvariants, including BA.2.75.2, BA.4.6. and BQ.1.1. The subvariants BA.2.75.2 and BQ.1.1 are expected to become predominant in many countries in November 2022. They carry an additional and often redundant set of mutations in the spike, likely responsible for increased transmissibility and immune evasion. Here, we established a viral amplification procedure to easily isolate Omicron strains. We examined their sensitivity to 6 therapeutic monoclonal antibodies (mAbs) and to 72 sera from Pfizer BNT162b2-vaccinated individuals, with or without BA.1/BA.2 or BA.5 breakthrough infection. Ronapreve (Casirivimab and Imdevimab) and Evusheld (Cilgavimab and Tixagevimab) lost any antiviral efficacy against BA.2.75.2 and BQ.1.1, whereas Xevudy (Sotrovimab) remained weakly active. BQ.1.1 was also resistant to Bebtelovimab. Neutralizing titers in triply vaccinated individuals were low to undetectable against BQ.1.1 and BA.2.75.2, 4 months after boosting. A BA.1/BA.2 breakthrough infection increased these titers, which remained about 18-fold lower against BA.2.75.2 and BQ.1.1, than against BA.1. Reciprocally, a BA.5 breakthrough infection increased more efficiently neutralization against BA.5 and BQ.1.1 than against BA.2.75.2. Thus, the evolution trajectory of novel Omicron subvariants facilitated their spread in immunized populations and raises concerns about the efficacy of most currently available mAbs.N

Mesure de la qualité de vie dans les maladies chroniques (étude transversale descriptive comparant des patients séropositifs pour le VIH traités par antirétroviraux à des patients insulinodépendants)

TOURS-BU Médecine (372612103) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Perceptions par les patients infectés par le VIH du rôle du médecin généraliste et des autres professionnels de santé dans la prise en charge de leur maladie en ville (étude qualitative par entretiens semi-directifs associée à une étude quantitative multicentrique par auto-questionnaires)

TOURS-BU Médecine (372612103) / SudocSudocFranceF

Retrospective and prospective studies evaluating the performance of the SARS-Cov-2 “AQ+ COVID-19 Ag Rapid Test” from InTec on symptomatic and non-symptomatic patients

For the last two years, the SARS-CoV-2 virus spread all around the world and led to the COVID-19 pandemic. The need of methods to control the pandemic and to propose rapid and efficient diagnostic tools has emerged. In this perspective, SARS-CoV-2 rapid antigen detection tests (RADT) have been developed. We performed a retrospective study on 638 collected nasopharyngeal samples used for reference RT-qPCR diagnosis to compare the AQ + COVID-19 Ag Rapid Test” from InTec (AQ + InTec test) performance with other commercially available RADT (Abbott Panbio, Roche SDBiosensor and Siemens Clinitest). We analysed the sensitivity and specificity of the different tests and showed a better overall performance of the AQ + InTec test, which was confirmed on the SARS-Cov-2 Omicron variant. We then conducted a prospective study on 844patients, to evaluate the sensitivity and specificity of the AQ + InTec test on nasal and nasopharyngeal samples in a point of care setting. We showed that sensitivity and specificity reach acceptable criteria (respectively 94.4% and 99.6% on nasal samples) regarding the official recommendations of the MDCG 2021-21 in both symptomatic and asymptomatic patients. Overall, the results of these two studies confirm that the AQ + InTec test is a valuable tool for testing in a pandemic context with a high proportion of asymptomatic patients who are potential carriers for the SARS-CoV-2 virus and is performant on the most current circulating variant Omicron

Lectin Analysis of SARS-CoV-2-Positive Nasopharyngeal Samples Using GLYcoPROFILE^® Technology Platform

Nasopharyngeal samples are currently accepted as the standard diagnostic samples for nucleic acid amplification testing and antigenic testing for the SARS-CoV-2 virus. In addition to the diagnostic capacity of SARS-CoV-2-positive crude nasopharyngeal samples, their qualitative potential for direct glycan-specific analysis, in order to uncover unique glycol profiles, was assessed. In this study we provide glycan characterization of SARS-CoV-2-positive and -negative nasopharyngeal samples directly from lectin interactions. Although with limited throughput, this study evaluated the clinical sensitivity and specificity of the GLYcoPROFILE® technology platformon45crude nasopharyngeal samples collected between November 2020 and April 2022. Each GLYcoPROFILE® of 39 SARS-CoV-2-positive samples was compared toglycoprofiling on a panel of 10 selected lectins and the results were paralleled with SARS-CoV-2-negative samples’ results. The GLYcoPROFILE® showed a clear distinction between positive and negative samples with WFA, GSL-II, PHA-L (GlcNAc-specific) and BPA (GalNAc-specific) highlighted as relevant lectins in SARS-CoV-2-positive samples. In addition, a significant, positive statistical correlation was found for these lectins (p < 0.01)

Quality control of antibiotics before the implementation of an STD program in Northern Myanmar.

BACKGROUND: The ready availability of poor-quality drugs in developing countries leads to treatment failure and, consequently, excess mortality and morbidity. Moreover, the widespread availability of substandard drugs plays a key role in increasing the resistance to antimicrobial drugs.GOAL As a prerequisite to the establishment of a sexually transmitted disease (STD) control program, this study aimed to evaluate the quality of antibiotics recommended for treatment of STDs that were locally available in the capital of a province of Northern Myanmar. STUDY DESIGN: In addition to the hospital pharmacy, we selected at random 5 of the 41 drug sellers and 5 of the 40 general practitioners who sell antibiotics in the city of Myitkyina. Twenty-one marketing products corresponding to nine different antibiotics used for STD treatment were purchased (benzathine benzylpenicillin, benzylpenicillin, ceftriaxone, chlortetracycline, ciprofloxacin, clotrimazole, co-trimoxazole, doxycycline, and erythromycin). Drugs were sent to France, where they were analyzed according to the WHO guidelines. Drugs were considered to be standard if their dosage remained in the 10% range of the expected value. RESULTS: Among the 21 different specialty products, only three displayed the official "registered" label. Three drugs were expired and the expiration date was not available for six others. One product did not contain the active drug declared (chlortetracycline; Lombisin, Unicorn, China) and did not show any in vitro activity against bacteria. Seven of 21 products (33%) did not contain the stated dosage (1, more than stated dosage; 6, less than stated dosage). The highest deficit observed was 48% in two products (co-trimoxazole, Yong Fong, Myanmar; benzylpenicillin, China [city and manufacturer unknown]). The dosage was not available for five drugs. As a result, only 8 of 21 products (38%) did not contain the stated dosage of active drug. CONCLUSION: These findings suggest that public health policies based on national treatment guidelines should rigorously include the monitoring of quality control of available antimicrobial products. In the absence of such measures, specific treatment strategies are likely to fail and to generate drug resistance