Incidence and factors associated with PrEP discontinuation in France.

OBJECTIVES: HIV pre-exposure prophylaxis (PrEP) is effective in preventing HIV, but some seroconversions occur due to poor adherence or PrEP discontinuation. Our objective was to estimate the incidence of PrEP discontinuation and describe the reasons and factors associated with discontinuations. METHODS: A retrospective cohort was conducted in three French hospitals between January 2016 and June 2022. PrEP users who attended at least twice within 6 months during study period were included and followed up until December 2022. The incidence rate of PrEP discontinuation was estimated by censoring lost to follow up individuals. Factors associated with PrEP discontinuations were identified using a multivariate Cox model. RESULTS: A total of 2785 PrEP users were included, with 94% men and 5% transgender people. Median age was 35 years. By December 2022, 653 users had stopped PrEP (24%). The incidence rate was 10.8 PrEP discontinuations for 100 person-years (PY). The main causes of discontinuation were being in a stable relationship (32%), and not judging the treatment useful anymore (12%). Individuals who discontinued PrEP were younger [<29, HR = 1.45 (1.17-1.80)], and more likely to be women [HR = 2.44 (1.50-3.96)] or sex workers [HR = 1.53 (0.96-2.44)]. They were more likely to report PrEP side effects [HR = 2.25 (1.83-2.77)] or ≥2 sexually transmitted infections [HR = 1.87 (1.53-2.27)] during the last year. CONCLUSION: The incidence of PrEP discontinuations was quite low compared to rates observed in other cohorts. Users who stopped PrEP were sometimes still exposed to HIV, emphasizing the need for targeted interventions to prepare and support PrEP discontinuations and limit seroconversion risk.

Clinical characteristics of ambulatory and hospitalized patients with monkeypox virus infection: an observational cohort study.

OBJECTIVES: A global outbreak of monkeypox virus infections in human beings has been described since April 2022. The objectives of this study were to describe the clinical characteristics and complications of patients with a monkeypox infection. METHODS: All consecutive patients with a polymerase chain reaction (PCR)-confirmed monkeypox infection seen in a French referral centre were included. RESULTS: Between 21 May and 5 July 2022, 264 patients had a PCR-confirmed monkeypox infection. Among them, 262 (262/264, 99%) were men, 245 (245/259, 95%) were men who have sex with men, and 90 (90/216, 42%) practiced chemsex in the last 3 months. Seventy-three (73/256, 29%) patients were living with human immunodeficiency virus infection, and 120 (120/169, 71%) patients were taking pre-exposure prophylaxis against human immunodeficiency virus infection. Overall, 112 (112/236, 47%) patients had contact with a confirmed monkeypox case; it was of sexual nature for 95% of the contacts (86/91). Monkeypox virus PCR was positive on the skin in 252 patients, on the oropharyngeal sample in 150 patients, and on blood in eight patients. The majority of patients presented with fever (171/253, 68%) and adenopathy (174/251, 69%). Skin lesions mostly affected the genital (135/252, 54%) and perianal (100/251, 40%) areas. Overall, 17 (17/264, 6%) patients were hospitalized; none of them were immunocompromised. Complications requiring hospitalization included cellulitis (n = 4), paronychia (n = 3), severe anal and digestive involvement (n = 4), non-cardia angina with dysphagia (n = 4), blepharitis (n = 1), and keratitis (n = 1). Surgical management was required in four patients. CONCLUSION: The current outbreak of monkeypox infections has specific characteristics: it occurs in the men who have sex with men community; known contact is mostly sexual; perineal and anal areas are frequently affected; and severe complications include superinfected skin lesions, paronychia, cellulitis, anal and digestive involvement, angina with dysphagia, and ocular involvement.

Histological Features Associated With Human Mpox Virus Infection in 2022 Outbreak in a Nonendemic Country.

Skin histology of papules and pustules from 5 men having sex with men with mpox infection showed viral intracytoplasmic cytopathic changes, interface dermatitis, marked inflammatory dermic infiltrate including superficial neutrophils and perivascular and periadnexal deep lymphocytes. Histologic description of mpox lesions improves our understanding about clinical presentations and may have some therapeutic implications.

Risk Factors Associated with Severe/Critical COVID-19 in People Living with HIV-1.

INTRODUCTION: Our objective was to determine the risk factors of a "severe/critical" form of COVID-19 in a cohort of people living with HIV-1 (PLWH1) followed in the Bichat University Hospital center in PARIS, FRANCE. METHODS: This study was an observational retrospective monocentric cohort of PLWH1 diagnosed with COVID-19 between February 1 st and November 31 st, 2020. Risk factors associated with "severe/critical" forms were determined using stepwise forward selection. RESULTS: One-hundred-and-twenty-nine PLWH1 with COVID-19 were included. COVID-19 diagnosis was confirmed in 98 cases (75.9%) and deemed probable according to the association of clinical criteria and contact case in 31 cases (24.1%). Clinical presentation of COVID-19 was "asymptomatic/mild/moderate" in 95 (73.6%), "severe" in 26 (21.7%) and "critical" in eight (6%). Patients with "severe/critical" COVID-19 tended to be older (median 54 year old), have a higher BMI (median 28.8 kg/m²) and were likely to have diabetes (9 versus 5) or chronic kidney disease (5 versus 2). Transgender women had higher risk too (OR: 4.9 (IC95: 1.35-24.0)). No association was observed between severity of COVID-19 and viral suppression or CD4 rates. CONCLUSION: Risk factors for severe COVID-19 were similar in PLWH1 than in the general population and PLWH1 transgender women were at higher risk.

Flame Retardancy and Excellent Electrical Insulation Performance of RTV Silicone Rubber.

Room temperature vulcanized (RTV) silicone rubber filled with aluminum trihydrate (ATH) is substantially engaged in electrical outdoor insulation applications. The pristine silicone rubber is highly combustible. ATH filled silicone rubber offers excellent electrical insulation but lacks in providing adequate flame retardancy. This short communication reports the novel results on improved flame retardancy of pristine and ATH filled silicone rubber whilst retaining the electrical insulation properties to a great extent. Results suggest that the presence of only one percent of graphene nanoplatelets with ATH sharply reduces the heat release rate and rate of smoke release. A minor reduction in dielectric breakdown strength and volume resistivity is noticed. Furthermore, permittivity and dielectric loss at power frequency suggest that a marginal 1% concentration of nanoplatelet with ATH is an excellent approach to fabricate flame retardant silicone rubber with an acceptable electrical insulation level.

Contribution of rapid lateral flow assays from capillary blood specimens to the diagnosis of COVID-19 in symptomatic healthcare workers: a pilot study in a university hospital, Paris, France.

BACKGROUND: This study aimed to assess, by rapid tests, the immune status against COVID-19 among Healthcare Workers (HCW) with history of symptoms, and for whom SARS-CoV-2 detection was either not documented or negative. METHODS: Whole blood by finger prick and serum samples were taken from HCW for use with 2 rapid lateral flow tests and an automated immunoassay. RESULTS: Seventy-two HCWs were included, median duration between symptoms onset and serology sampling was 68 days. Anti-SARS-CoV-2 antibodies were detected by rapid test in 11 HCW (15.3%) and confirmed in the 10 with available serum by the automated immunoassay. The frequency of ageusia or anosmia was higher in participants with SARS-CoV-2 antibodies (P = 0.0006 and P = 0.029, respectively). CONCLUSIONS: This study, among symptomatic HCW during the first wave in France, showed that 15% had IgG anti-SARS-CoV-2, a higher seroprevalence than in the general population. Rapid lateral flow tests were highly concordant with automated immunoassay.

A study of pathological characteristics and BRAF V600E status in Langerhans cell histiocytosis of Vietnamese children.

BACKGROUND: Langerhans cell histiocytosis (LCH) is more common in children than adults and involves many organs. In children, the BRAF V600E mutation is associated with recurrent and high-risk LCH. METHODS: We collected paraffin blocks of 94 pediatric LCH patients to detect BRAF V600E mutation by sequencing. The relationship between BRAF V600E status and clinicopathological parameters were also critically analyzed. RESULTS: BRAF V600E mutation exon 15 was detected in 45 cases (47.9%). Multiple systems LCH showed a significantly higher BRAF V600E mutation rate than a single system (p=.001). No statistical significance was evident for other clinical characteristics such as age, sex, location, risk organs involvement, and CD1a expression. CONCLUSIONS: In Vietnamese LCH children, the proportion of BRAF V600E mutational status was relatively high and related to multiple systems.

Pre-exposure HIV prophylaxis (PrEP) among transgender women: 3 years of follow-up in a university hospital in Paris.

OBJECTIVES: The principal outcome was to describe clinical characteristics of a transgender male-to-female (TGW) cohort followed for pre-exposure HIV prophylaxis (PrEP). INTRODUCTION: Few efforts and preventive interventions have targeted transgender population, despite them being at great risk of HIV infection. METHODS: This was a retrospective transgender male-to-female (TGW) cohort followed for PrEP at Bichat Hospital Sexual Health Clinic between February 2016 and January 2019.The principal outcome was to describe clinical characteristics of this TGW population: modalities of PrEP uptake, treatment adherence and tolerance, sanitary system retention, hormonal therapy and STIs.Data about age, ethnicity, language, sex work and sanitary healthcare insurance coverage were also collected. RESULTS: Forty-nine TGW were included, with a median age of 33 years; 43/49 (87.7%) were from South America and 43/49 (87.7%) were sex workers. Forty-four 44/49 TGW (89.7%) had no regular healthcare insurance coverage. Nineteen out of 49 (38.7%) had a history of STI in the last 12 months. Hormone intake was reported in 16/49 (32.60%). PrEP with oral TDF/FTC was prescribed on a daily basis for 45/49 TG (91.8%). Two TGW discontinued PrEP for gastrointestinal intolerance. No case of renal toxicity or HIV seroconversion has been reported. Retention rate was high (71.4%), but average follow-up was 9 months. CONCLUSIONS: Our data showed a very vulnerable population, with a high proportion of migrants, sex workers and with a low healthcare insurance coverage. Retention rate was high (71.4%). Further multi-component interventions are needed to improve global sex health approach, PreP follow-up and sanitary system retention among TGW population.

Simulation and Experimental Investigation on Carbonized Tracking Failure of EPDM/BN-based Electrical Insulation.

* Correspondence: tariq [...].

Incidence of and risk factors for medical care interruption in people living with HIV in recent years.

OBJECTIVES: With HIV treatment as a prevention strategy, retention in care remains a key for sustained viral suppression. We sought to identify HIV-infected patients at risk for medical care interruption (MCI) in a high-income country. METHODS: The HIV-infected patients enrolled had to attend the clinic at least twice between January 2010 and October 2014 and were followed up until May 2016. MCI was defined as patients not seeking care in or outside the clinic for at least 18 months, regardless of whether they returned to care after the interruption. The association between MCI and sociodemographic, clinical, and immuno-virological characteristics at HIV diagnosis and during follow-up was assessed using Cox models. RESULTS: The incidence rate of MCI was 2.5 per 100 persons-years (95% confidence interval [CI] = 2.3-2.7). MCI was more likely in patients who accessed care >6 months after diagnosis (hazard ratio [HR] = 1.30, 95% CI = 1.10-1.54 vs. ≤6 months) or did not report a primary care physician (HR = 2.40; 95% CI = 2.03-2.84). MCI was less likely in patients born in sub-Saharan Africa (HR = 0.75, 95% CI = 0.62-0.91 vs. born in France). During follow-up, the risk of MCI increased when the last CD4 count was ≤350 (HR = 2.85, 95% CI = 2.02-4.04 vs. >500 cells/mm3) and when the patient was not on antiretroviral therapy (HR = 3.67, 95% CI = 2.90-4.66). CONCLUSIONS: The incidence of MCI is low in this hospital that serves a large proportion of migrants. Low or no recorded CD4 counts for a medical visit could alert of a higher risk of MCI, even more in patients who accessed HIV care late or did not report a primary care physician.

Metabolic syndrome and endocrine status in HIV-infected transwomen.

BACKGROUND: HIV-infected transwomen face multiple specific issues. Economic and social marginalization, sex work, substance abuse, hormonal consumption and silicone injection may affect the course of HIV infection and lead to metabolic and endocrine complications. METHODS: A matched case-control study was performed between 2013 and 2015 in a University Hospital and compared metabolic syndrome (MetS), thyroid and adrenal functions in HIV-infected transwomen (i.e. cases) and cisgender HIV-infected men (i.e. controls) matched for age and antiretroviral therapy. The interaction between hormonal consumption, the course of HIV infection and antiretroviral therapy was also studied. Clinical and biological data (CD4 cell count, HIV RNA load, antiretroviral plasma drug concentration, HDL, triglycerides, glucose, cortisol, thyroid stimulating hormone, free thyroxine, prolactine) were measured. RESULTS: A total of 292 HIV-infected patients (100 cases and 192 controls) were prospectively included. There was no difference between the two populations in terms of frequency of MetS, but subclinical hypothyroidism and adrenal insufficiency were more frequent in cases than in controls with, respectively, 12 vs. 3% (P < 0.002) for hypothyroidism and 20 vs. 8% (P < 0.001) for adrenal insufficiency. Prolactinemia, only performed in transwomen, was often elevated (21%) but rarely confirmed as true active hyperprolactinemia (monomeric form) (3%). Although hormonal intake was frequent among transwomen (31%), no impact on antiretroviral bioavailability and efficacy was detected. CONCLUSION: In this study, no increase in the prevalence of MetS was detected in HIV-infected transwomen patients. In contrast, adrenal and thyroid functions abnormalities were frequent and should be systematically assessed in this population. No impact of hormonal intake on antiretroviral bioavailability and efficacy was detected.

Orogenital Transmission of Neisseria meningitidis Causing Acute Urethritis in Men Who Have Sex with Men.

Neisseria meningitidis sequence type 11 is an emerging cause of urethritis. We demonstrate by using whole-genome sequencing orogenital transmission of a N. meningitidis sequence type 11 isolate causing urethritis in a monogamous couple of men who have sex with men. These results suggest dissemination of this clonal complex among low-risk patients.

High virological suppression regardless of the genotypic susceptibility score after switching to a dolutegravir-based regimen: week 48 results in an observational cohort.

Objectives: To assess, in a clinical cohort, the efficacy of switching current ART in virologically suppressed patients to a dolutegravir-based regimen, regardless of the genotypic susceptibility score (GSS). Patients and methods: This was an observational single-centre study assessing ART-treated patients with plasma viral load (pVL) <50 copies/mL who were switched to a dolutegravir-based regimen with 1 year of follow-up. PCR negative was defined as an undetected PCR signal. Trough plasma concentration (C24) was determined using UPLC-MS/MS. Results: Two hundred and thirty-nine patients initiated a dolutegravir-based regimen: 12%, 29% and 59% had a total GSS of 1 or 1.5 (group 1), 2 or 2.5 (group 2) and 3 (group 3), respectively. At switch initiation, the median time since first ART and the median duration with pVL <50 copies/mL were 13 years (IQR = 6-19) and 3 years (IQR = 1-6), respectively. Median times since last genotype were 9, 10 and 5 years for groups 1, 2 and 3, respectively. Twenty patients (8.4%) discontinued the dolutegravir-based regimen due to adverse events. During the study, 96.4% (n = 661/686) of all pVL were <50 copies/mL. Four patients (1.7%) experienced virological failure (two pVL >50 copies/mL) without emergence of resistance; these patients' GSSs were 2, 2.5, 3 and 3. The median dolutegravir C24 was 1545 ng/mL (IQR = 1150-2097). Of the patients with pVL <20 copies/mL, 72% were PCR negative during the follow-up, with no difference between the three groups of patients. Conclusions: This observational cohort study showed a high level of virological suppression maintenance in the first year following the switch to a dolutegravir-based regimen, even in patients with GSS ≤2.

Leigh syndrome T8993C mitochondrial DNA mutation: Heteroplasmy and the first clinical presentation in a Vietnamese family.

Leigh syndrome is a rare inherited, heterogeneous and progressive neurometabolic disorder that is mainly caused by specific mutations in nuclear DNA (nDNA) or mitochondrial DNA (mtDNA). The present study reported a case of childhood Leigh syndrome with a point mutation at bp 8,993 in the mitochondrial ATPase6 gene. A 21­month­old male child had developed epilepsy, muscular weakness and vomiting, which was accompanied by high fever. Magnetic resonance imaging indicated typical characteristics of Leigh syndrome, including a symmetric abnormal signal in the dorsal medulla oblongata and Sylvian fissure enlargement in association with an abnormal signal in the periventricular white matter and in the putamina and caudate heads. The diagnosis was further supported with genetic tests including polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), sequencing, and quantitative PCR. The patient was found to carry a mitochondrial T8993C (m.T8993C) mutation in peripheral blood with 94.00±1.34% heteroplasmy. Eight of his relatives were also subjected to quantification of the m.T8993C mutation. The percentages of heteroplasmy in samples taken from the grandmother, mother, aunt, cousin 1, and cousin 2 were 16.33±1.67, 66.81±0.85, 71.66±3.22, 87.00±1.79, and 91.24±2.50%, respectively. The mutation was not found in samples taken from the father, the husband of the aunt, or the grandfather of the patient. The obtained data showed that the mutation was maternally inherited and accumulated through generations. Even though the heteroplasmy levels of his mother, aunt, cousin 1, and cousin 2 were relatively high (66.81­91.24%), they remained asymptomatic, indicating that the threshold at which this mutation shows effects is high. To the best of our knowledge, this is the first report of a case of Leigh syndrome in a Vietnamese individual harboring a mtDNA mutation at the 8,993 bp site, and showing a correlation between the heteroplasmy and clinical phenotype. These findings may be useful in helping to improve the clinical diagnosis and treatment of Leigh syndrome.

Use of PCR Signal and Therapeutic Drug Monitoring in a Switch Cohort Study to Tenofovir/Emtricitabine/Rilpivirine: A W96 Follow-Up.

OBJECTIVE: To assess, in a clinical cohort, the efficacy of switching treatment in virologically-suppressed patients to tenofovir/emtricitabine/rilpivirine as a single-tablet regimen (STR) using the PCR signal of the viral load (VL) assay and plasma drug determination (C24h). PATIENTS AND METHODS: An observational single-centre study enrolling patients with VL<50 copies/mL initiating rilpivirine-based STR. C24h and VL were performed until W48 and W96 of STR, respectively. PCRneg was defined as an undetected PCR signal. Medians (IQR) were presented. RESULTS: 116 patients were enrolled. At STR baseline, time since first antiretroviral therapy and time of virological suppression were 6 years (2-9) and 17 months (7-43), respectively. Before STR initiation, patients were receiving protease inhibitors and non-nucleoside reverse transcriptase inhibitors-based regimen in 44% and 47% of cases, respectively. Historical genotype showed virus resistant to one drug of the STR in 6 patients (5%). At W96, 17 (15%) discontinued STR due to adverse events. The proportion of patients maintaining VL <50 copies/mL on treatment was 98%, 99%, 100%, 100%, 100% and 100% at W12, W24, W36, W48, W72 and W96, respectively. Among them, 70%, 66%, 68%, 59%, 74%, 68% and 60% were PCRneg at baseline, W12, W24, W36, W48, W72 and W96, respectively. Median rilpivirine C24h was 91 ng/mL (57-141, n = 285), with 91% of rilpivirine C24h >50 ng/mL, the target effective concentration. CONCLUSIONS: In this clinical cohort of virologically-suppressed patients switching to a new STR, most subjects had adequate rilpivirine C24h and displayed a high level of virological suppression with no residual viremia until W96.

Hepatitis B and human immunodeficiency virus co-infection.

Hepatitis B and human immunodeficiency virus (HBV and HIV) infection share transmission patterns and risk factors, which explains high prevalence of chronic HBV infection in HIV infected patients. The natural course of HBV disease is altered by the HIV infection with less chance to clear acute HBV infection, faster progression to cirrhosis and higher risk of liver-related death in HIV-HBV co-infected patients than in HBV mono-infected ones. HIV infected patients with chronic hepatitis B should be counseled for liver damage and surveillance of chronic hepatitis B should be performed to screen early hepatocellular carcinoma. Noninvasive tools are now available to evaluate liver fibrosis. Isolated hepatitis B core antibodies (anti-HBc) are a good predictive marker of occult HBV infection. Still the prevalence and significance of occult HBV infection is controversial, but its screening may be important in the management of antiretroviral therapy. Vaccination against HBV infection is recommended in non-immune HIV patients. The optimal treatment for almost all HIV-HBV co-infected patients should contain tenofovir plus lamivudine or emtricitabine and treatment should not be stopped to avoid HBV reactivation. Long term tenofovir therapy may lead to significant decline in hepatitis B surface Antigen. The emergence of resistant HBV strains may compromise the HBV therapy and vaccine therapy.

Vaccination against viral hepatitis of HIV-1 infected patients.

Reciprocal interactions between HIV and HAV or HBV can increase risk of morbidity and mortality in HIV disease and/or worsened the natural course of the hepatitis viruses. Hepatitis A vaccination is recommended for HIV infected patients at risk for exposure or severe disease: men who have sex with men, injecting drug users, patients with chronic liver disease and patients traveling in high endemic countries. As for healthy adults the scheme of vaccination is two doses 6 or 12 mo apart, nevertheless, seroconversion rates are lower. A third dose could improve the seroconversion rates. Hepatitis B vaccination is recommended for all HIV infected persons lacking prior immunity. As the immune response to hepatitis B vaccines is impaired in HIV-infected adults, four double doses of hepatitis B vaccine could enhance serological response. To assume a higher immune response, vaccines should be administered in HIV-infected patients with undetectable HIV viral load and high CD4 cell count.

Darunavir: an effective protease inhibitor for HIV-infected patients.

Darunavir is a new-generation nonpeptidic HIV protease inhibitor (PI), used with low doses of ritonavir for pharmacologic enhancement (boosting). It has demonstrated potent activity against multidrug-resistant HIV, with a robust resistance profile and a distinct set of mutations. In heavily treatment-experienced patients with HIV infection, darunavir administered twice daily with ritonavir has shown higher rates of efficacy than the control PI. In less treatment-experienced patients, boosted darunavir was noninferior to boosted lopinavir. In treatment-naive patients, boosted darunavir administered once daily was noninferior to boosted lopinavir, and showed higher virologic and immunological response rates in patients with high baseline viral load and low baseline CD4(+) cell counts. Monotherapy with boosted darunavir is an acceptable option in some specific conditions. Boosted darunavir was generally well tolerated, with lower incidence of diarrhea and a more favorable lipid profile than boosted lopinavir in treatment-naive patients.