Comparison of the Alinity M STI with the GeneXpert CT/NG for the detection of sexually transmitted microorganisms.

We assess the performances of the Alinity M STI assay (Abbott Molecular) in comparison to the Xpert CT/NG assay (Cepheid). We first retrospectively used a collection of 70 frozen samples of which 33, 31, and 6 were positives for Chlamydia trachomatis (CT), Neisseria gonorrhoea (NG), and both micro-organisms respectively. The Alinity M STI and the Xpert CT/NG results were in accordance for all. The mean difference in cycle threshold values between the Xpert CT/NG and the Alinity M STI were -1.6 and 0.0 for CT and NG respectively. Then 214 fresh samples collected from 121 patients were prospectively tested with both instruments. Anal swabs, throat swabs, vaginal swabs, and urines accounted each for about 25%. Seven (3.2%) samples of which 5 anal swabs, provided inconclusive results with the Alinity M STI. In conclusion, the Alinity M STI is an accurate device for the microbiological diagnosis of NG and CT infections.

Monkeypox Virus Infection in 18-Year-Old Woman after Sexual Intercourse, France, September 2022.

A monkeypox virus outbreak has spread worldwide since April 2022. We report a young woman in France positive for monkeypox virus transmitted through oral and vaginal sex. Ulceronecrotic lesions developed intravaginally and around her vulva. Health professionals should become familiar with all aspects of infection from this virus, including possible vertical transmission.

Monkeypox Vaccine Hesitancy in French Men Having Sex with Men with PrEP or Living with HIV in France.

People with pre-exposure prophylaxis (PrEP) or living with HIV are a high-risk population for monkeypox virus (MPXV) infection. It is important to achieve high MPXV vaccination coverage rates in this group. This project used self-reporting to assess vaccine hesitancy for the smallpox vaccine and acceptance among men having sex with men with PrEP or living with HIV. In total, 52 (33.6%) participants among the 155 declared their hesitancy to be vaccinated against MPXV. Moreover, 20.7% patients with PrEP declared a hesitant attitude towards the smallpox vaccine compared to 40.2% of the HIV patients, p = 0.013. This difference remained not significant after adjustment for age (p = 0.119) and after adjustment for both age and number of different sexual partners (p = 0.406). Among PrEP people, those who expressed concerns about people getting more vaccines than needed (p = 0.012) were less likely to accept vaccination, whereas an increased number of different sexual partners during the previous month was significantly associated with acceptance of vaccination (p = 0.034). Among HIV people, those who expressed concerns about being infected by MPXV (p < 0.001), those who expressed that the smallpox vaccine should be compulsory for people at risk (p < 0.001) and those with an increased the number of different sexual partners the previous month (p = 0.018) were significantly associated with higher acceptance of MPXV vaccination. Our results suggest that vaccine strategy would be efficient in France with a communication strategy emphasizing the benefits of vaccination and the potential MPXV risk infection for health in PrEP and HIV people. Other preventive actions should be implemented, including reduction in sexual partners.

Electronic medical record alert increases HIV screening rates: the Foch hospital pilot POP-up project.

BACKGROUND: Despite significant national human immunodeficiency virus (HIV) screening activity, there are persistent delays in screening, and many missed diagnostic opportunities. To facilitate targeted screening, an electronic medical record (EMR) alert reminder was applied in the Foch hospital. Screening rates after implementation were reported. METHODS: A prospective cohort analysis was performed in Foch Hospital between 24 April 2018 and 4 October 2019 among hospitalized patients born in high HIV prevalence countries and/or having social vulnerability criteria (universal health coverage). From the admissions software, when specific low health coverage was provided and/or high-prevalence country of birth was registered, an electronic alert (EMR alert) appeared on the ward where the patient was hospitalized. The EMR alert database was examined for HIV screening and activity responses from each service of the Hospital. RESULTS: Eight thousand one hundred eighty-one alerts were recovered during the period for 1448 patients. 27 services used the EMR alert. Most of the alerts were directly closed (74.4%), 14.5% of the alerts were closed due to doctors declaring that they did not have time to respond. 297 (3.6%) of the 8181 alerts resulted in a prescription of HIV serology corresponding for 20.5% of the patients. CONCLUSION: EMR alert can help to increase the rate of HIV screening in hospital care practice. Through this EMR alert system, HIV screening can be implemented as a common practice like any other medical alternative. Future research should examine the factors influencing physicians' attitudes to this alert system to improve the HIV screening rate.

An Immunogenicity Report for the Comparison between Heterologous and Homologous Prime-Boost Schedules with ChAdOx1-S and BNT162b2 Vaccines.

BACKGROUND: There is a small amount of immunological data on COVID-19 heterologous vaccination schedules in humans. We assessed the immunogenicity of BNT162b2 (Pfizer/BioNTech) administered as a second dose in healthcare workers primed with ChAdOx1-S (Vaxzevria, AstraZeneca). METHODS: 197 healthcare workers were included in a monocentric observational study in Foch hospital, France, between June and July 2021. The main outcome was the immunogenicity measured by serum SARS-CoV-2 IgG antibodies. RESULTS: 130 participants received the ChAdOx1-S/BNT vaccine and 67 received the BNT/BNT vaccine. The geometric mean of IgG antibodies was significantly higher in the BNT/BNT vaccine group compared to the ChAdOx1-S/BNT vaccine group, namely 10,734.9, 95% CI (9141.1-12,589.3) vs. 7268.6, 95% CI (6501.3-8128.3), respectively (p < 0.001). However, after adjustment for time duration between the prime and second vaccinations, no significant difference was observed (p = 0.181). A negative correlation between antibody levels and time duration between second dose and serology test was observed for the BNT/BNT vaccine (p < 0.001), which remained significant after adjustment for all covariates (p < 0.001), but not for the ChAdOx1-S/BNT vaccine (p = 0.467). CONCLUSIONS: Heterologous and homologous schedules of ChAdOx1-S and BNT vaccines present robust immune responses after the second vaccination. The results observed were equivalent after adjustment for covariates and emphasize the importance of flexibility in deploying mRNA and viral vectored vaccines. Nevertheless, applying the ChAdOx1-S schedule vaccination for the heterologous second dose of BNT was associated with decreased IgG antibody levels compared to the homologous BNT/BNT vaccination.

COVID-19 Vaccine Hesitancy among French People Living with HIV.

People living with HIV are a high-risk population concerning the coronavirus 19 (COVID-19) infection, with a poorer prognosis. It is important to achieve high COVID-19 vaccination coverage rates in this group as soon as possible. This project used self-reporting to assess vaccine hesitancy and acceptance among people living with HIV towards the novel COVID-19 vaccine. Sixty-eight (28.7%) participants among the 237 declared their hesitancy to be vaccinated against COVID-19. Participants who expressed concerns about their health (p < 0.001), the requirement of mandatory COVID-19 vaccination (p = 0.017), and their chronic disease status (p = 0.026) were independently associated with the acceptance of vaccination. Conversely, participants presenting general vaccine refusal (p < 0.001), concerns about the serious side effects of COVID-19 vaccines (p < 0.001), and those already thinking having an immune status to COVID-19 (p = 0.008) were independently associated with COVID-19 vaccine hesitancy. Our results suggest that vaccine strategy would be more successful in France with a communication strategy emphasizing the collective benefits of herd immunity in the population living with HIV and reassuring patients with chronic diseases about the safety of the proposed vaccines.

Tocilizumab for Severe Worsening COVID-19 Pneumonia: a Propensity Score Analysis.

BACKGROUND: High levels of serum interleukin-6 (IL-6) correlate with disease severity in COVID-19. We hypothesized that tocilizumab (a recombinant humanized anti-IL-6 receptor) could improve outcomes in selected patients with severe worsening COVID-19 pneumonia and high inflammatory parameters. METHODS: The TOCICOVID study included a prospective cohort of patients aged 16-80 years with severe (requiring > 6 L/min of oxygen therapy to obtain Sp02 > 94%) rapidly deteriorating (increase by ≥ 3 L/min of oxygen flow within the previous 12 h) COVID-19 pneumonia with ≥ 5 days of symptoms and C-reactive protein levels > 40 mg/L. They entered a compassionate use program of treatment with intravenous tocilizumab (8 mg/kg with a maximum of 800 mg per infusion; and if needed a second infusion 24 to 72 h later). A control group was retrospectively selected with the same inclusion criteria. Outcomes were assessed at D28 using inverse probability of treatment weighted (IPTW) methodology. RESULTS: Among the 96 patients included (81% male, mean (SD) age: 60 (12.5) years), underlying conditions, baseline disease severity, and concomitant medications were broadly similar between the tocilizumab (n = 49) and the control (n = 47) groups. In the IPTW analysis, treatment with tocilizumab was associated with a reduced need for overall ventilatory support (49 vs. 89%, wHR: 0.39 [0.25-0.56]; p < 0.001). Albeit lacking statistical significance, there was a substantial trend towards a reduction of mechanical ventilation (31% vs. 45%; wHR: 0.58 [0.36-0.94]; p = 0.026). However, tocilizumab did not improve overall survival (wHR = 0.68 [0.31-1.748], p = 0.338). Among the 85 (89%) patients still alive at D28, patients treated with tocilizumab had a higher rate of oxygen withdrawal (82% vs. 73.5%, wHR = 1.66 [1.17-2.37], p = 0.005), with a shorter delay before being weaned of oxygen therapy (mean 11 vs. 16 days; p < 0.001). At D28, the rate of patients discharged from hospital was higher in the tocilizumab group (70% vs. 40%, wHR = 1.82 [1.22-2.75]; p = 0.003). The levels of CRP and fibrinogen post therapy (p < 0.001 for both variables) were significantly lower in the tocilizumab group (interaction test, mixed model). Rates of neutropenia (35% vs. 0%; p < 0.001) were higher in the tocilizumab group, yet rates of infections (22% vs. 38%, p = 0.089) including ventilator-acquired pneumonia (8% vs. 26%, p = 0.022) were higher in the control group. CONCLUSION: These data could be helpful for the design of future trials aiming to counter COVID-19-induced inflammation, especially before patients require admission to the intensive care unit.

De-simplifying single-tablet antiretroviral treatments for cost savings in France: From the patient perspectives to a 6-month follow-up on generics.

In developed countries, most people living with HIV/AIDS are treated with costly brand single-tablet regimens. Given the economic impact, French guidelines recommend using generic antiretroviral therapy when possible to decrease antiretroviral therapy costs. We aimed to study HIV-infected patients' acceptability to switch from a brand single-tablet regimens [abacavir/lamivudine/dolutegravir (Triumeq®) or emtricitabine/tenofovir disoproxil fumarate/rilpivirine (Eviplera®)] to a treatment comprising of two pills: one is a fixed-dose generic combination of 2 Nucleoside Analogs and the second tablet is the third antiretroviral. This study was a prospective observational study in a French hospital. During their follow-up, patients on stable single-tablet regimens were made aware of the possible cost-saving. They were questioned about their willingness and barriers accepting the substitution. Participants chose between the two regimens, either to remain on single-tablet regimens or switch to the de-simplified regimen. Six months later, a second survey was given to the patient who chose to de-simplify and HIV viral load was controlled. The study included 98 patients: 60 receiving emtricitabine/tenofovir disoproxil fumarate/rilpivirine (Eviplera®) and 38 on abacavir/lamivudine/dolutegravir (Triumeq®). Forty-five patients accepted the de-simplified treatment, 37 refused and 16 were undecided and followed the decision offered by their physician. The main reason for unwillingness to switch is the number of pills (77.3%). In multivariate model analysis, male patients (p = 0.001) who have taken antiretroviral therapy for over 20 years (p = 0.04) and who retrieve their treatment in their community hospital (p = 0.03) are more likely to accept the switch. Fifty-one patients accepted to replace their single-tablet regimens and six months later, the majority was satisfied; only four returned to single-tablet regimens because of suspected side effects. Half of the people living with HIV/AIDS in our cohort accepted to switch from brand single-tablet regimens to a two-tablet regimen containing generic drugs within a process that emphasizes health expenditure savings.

Immunohematologic tolerance of chronic transfusion exchanges with erythrocytapheresis in sickle cell disease.

BACKGROUND: Sickle cell disease (SCD) has become a major public health issue. Hydroxyurea and red blood cell (RBC) transfusion are the cornerstone treatments. Erythrocytapheresis (ECP) is an automated method for transfusion exchange. Given that ECP requires more blood than conventional transfusion, there is concern about alloimmunization and hemolytic transfusion reactions. We evaluate the incidence of hemolytic transfusion reactions and alloimmunization rates in patients receiving conventional blood transfusions and in patients participating in long-term blood exchange programs with ECP. STUDY DESIGN AND METHODS: All hemolytic transfusion reactions and alloimmunizations in SCD patients were recorded over the period 2006 to 2011. Conventional transfusions and ECP were compared. RESULTS: The cohort consisted of 188 SCD patients. The median (±SD) age was 23 (±14) years. The ECP and conventional transfusion groups comprised 49 and 139 patients, respectively. The prevalence of alloimmunization was 33% in the ECP group and 22% in the conventional transfusion group (p = 0.1797). The alloimmunization/RBC unit (RBCU) ratio was lower in the ECP group than in the conventional transfusion group (1.6 and 11.6 per 1000, respectively; p < 0.0001). Although patients in the ECP group received more than 10 times more RBCUs than patients in the conventional transfusion group (206 vs. 19 RBCUs per patient, respectively; p < 0.0001), none of the four recorded hemolytic transfusion reactions (n = 4) occurred. CONCLUSION: Regarding alloimmunization, ECP exhibits a good immunohematologic safety profile relative to conventional transfusion in a large SCD mainly adult cohort.

Clinical features and risk factors for atazanavir (ATV)-associated urolithiasis: a case-control study.

OBJECTIVES: Clinical features and risk factors for atazanavir (ATV)-associated urolithiasis have not been fully investigated. METHODS: We reviewed all cases of ATV-containing urolithiasis identified by infrared spectrophotometry among HIV-infected patients over a 5-year period to describe their clinical features and outcome. A case-control study was performed to identify risk factors associated with ATV-associated urolithiasis using univariate and multivariate logistic regression analyses. RESULTS: 30 cases of ATV-associated urolithiasis were analyzed. Patients were mostly men (87%), median age: 45.5 years, median CD4 cell count: 443 cells/µL and 97% had plasma HIV RNA level <50 cp/mL. Median time between the initiation of ATV-containing regimen and the diagnosis of urolithiasis was 3.1 years. Patients presented with flank pain in 90% and macroscopic hematuria in 82.6%, 34% had renal dysfunction and 44.8% needed ureteroscopic treatment. In univariate analysis, chronic hepatitis C, a history of urolithiasis, prior use of indinavir, ATV duration, undetectable plasma HIV RNA, use of ritonavir as a booster and serum free bilirubin level were associated with ATV-urolithiasis. Multivariate models retained serum free bilirubin level (OR: 2.31, p<0.02) and either ATV duration (OR:  = 1.42, p = <0.03) or a history of urolithiasis (OR = 4.79, p<0.02) when adjusting on serum free bilirubin level as risk factors associated with urolithiasis. CONCLUSIONS: ATV-containing urolithiasis are associated with frank clinical symptoms and may require surgical intervention. A high serum bilirubin level, a long exposure to ATV and a history of urolithiasis are risk factors for this rare adverse event.

Is clinical practice concordant with the changes in guidelines for antiretroviral therapy initiation during primary and chronic HIV-1 infection? The ANRS PRIMO and COPANA cohorts.

OBJECTIVE: Guidelines for initiating HIV treatment are regularly revised. We explored how physicians in France have applied these evolving guidelines for ART initiation over the last decade in two different situations: chronic (CHI) and primary HIV-1 infection (PHI), since specific recommendations for PHI are also provided in France. METHODS: Data came from the ANRS PRIMO (1267 patients enrolled during PHI in 1996-2010) and COPANA (800 subjects enrolled at HIV diagnosis in 2004-2008) cohorts. We defined as guidelines-inconsistent during PHI and CHI, patients meeting criteria for ART initiation and not treated in the following month and during the next 6 months, respectively. RESULTS: ART initiation during PHI dramatically decreased from 91% of patients in 1996-99 to 22% in 2007 and increased to 60% in 2010, following changes in recommendations. In 2007, however, after the CD4 count threshold was raised to 350 cells/mm(3) in 2006, only 55% of the patients with CD4≤350 were treated and 66% in 2008. During CHI, ART was more frequently initiated in patients who met the criteria at entry (96%) than during follow-up: 83% when recommendation to treat was 200 and 73% when it was 350 cells/mm(3). Independent risk factors for not being treated during CHI despite meeting the criteria were lower viral load, lower educational level, and poorer living conditions. CONCLUSION: HIV ART initiation guidelines are largely followed by practitioners in France. What can still be improved, however, is time to treat when CD4 cell counts reach the threshold to treat. Risk factors for lack of timely treatment highlight the need to understand better how patients' living conditions and physicians' perceptions influence the decision to initiate treatment.

Switching to darunavir/ritonavir 800/100 mg once-daily containing regimen maintains virological control in fully suppressed pre-treated patients infected with HIV-1.

The objective of this study was to evaluate the switch to once-daily darunavir/ritonavir 800/100 mg in treatment-experienced patients with suppressed HIV-1 replication on a twice-daily ritonavir-boosted protease-inhibitor (bid PI/r) containing regimen, that is in a setting where genotypic resistance test cannot be performed. In this open label, non-comparative, multicenter study, patients on a bid PI/r-containing triple combination, with suppressed viral replication, were switched to once-daily darunavir/r 800/100 mg containing triple combination. The primary endpoint was the proportion of patients with plasma HIV-RNA < 50 copies/ml 24 weeks after the switch. Intensive darunavir pharmacokinetic evaluation was performed at Week 4 (W4) in 11 patients. Eighty-five patients were enrolled. All had HIV-RNA < 50 copies/ml at screening with a pre-exposure to a median of 2 PI/r (1-5). By intent-to-treat analysis (missing = failure), 78/85 patients (92%, 95% CI [83;96]) maintained an HIV-RNA < 50 copies/ml at W24. Seven patients experienced protocol-defined treatment failure between baseline and W24: Two had confirmed low-level viral rebound, one discontinued study treatment for adverse event, three withdrew their consent, and one was lost to follow-up. By on-treatment analysis, 78/80 patients (97%, 95% CI [91;99]) maintained an HIV-RNA < 50 copies/ml at W24. Results were similar at Week 48. The median area under the darunavir plasma concentration-time curve measured in 11 patients was 61,380 ng hr/ml; darunavir median trough concentration 1,340 ng/ml and darunavir half-life was 12.2 hr. Tolerability of once-daily darunavir/r 800/100 mg was excellent. Optimally suppressed, treatment-experienced patients can switch safely from a twice-daily PI/r regimen to a once-daily darunavir/r 800/100 mg containing regimen.