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.

Broad-based SARS-CoV-2 testing program for healthcare workers in a primary care hospital in France.

A broad-based SARS-CoV-2 testing program for all symptomatic healthcare workers (HCWs) was implemented in Tenon hospital, Paris, France. From February 26 to April 22, 2020, 701 symptomatic HCWs were screened, of whom 247 (35.2%) tested positive for SARS-Cov-2. Myalgia, fever, anosmia and ageusia were associated with RT-PCR positivity. Testing of HCWs is an essential step toward control of the epidemic. Further studies could establish clinical algorithms for SARS-CoV-2 diagnosis to compensate for RT-PCR test and chest CT limits or unavailability.

Invasive Infections with Nannizziopsis obscura Species Complex in 9 Patients from West Africa, France, 2004-20201.

Nine new human invasive infections caused by the keratinophilic fungi Nannizziopsis obscura have been reported in France since 2004. The patients had variable clinical manifestations, had frequent dissemination, were mainly T-cell immunocompromised, and all originated from sub-Saharan West Africa. Before collection of the isolates, the etiologies of these infections were often misidentified, underscoring the extent of microscopic and cultural polymorphisms. All isolates but 1 had low MICs for the 8 antifungal drugs tested. When treated, patients received mainly azole therapy. Two of 7 patients with a known outcome died. We performed multilocus sequence analysis of N. obscura clinical strains and several strains of Nannizziopsis spp. isolated from reptiles. The human strains were clearly differentiated from the animal strains. N. obscura might be endemic to West Africa and responsible for undetected infections, which might become reactivated when immunosuppression occurs. N. obscura infection is probably underestimated because only sequencing enables proper identification.

Risk of Severe Bacterial Infection in People Living Human Immunodeficiency Virus Infection in the Combined Antiretroviral Therapy Era.

BACKGROUND: Severe bacterial infections are the first cause of morbidity in people with human immunodeficiency virus (PWH). We aimed to assess their incidence and to analyze their determinants. METHODS: We studied human immunodeficiency virus (HIV)-1-infected individuals aged at least 15 years and prospectively followed between 2006 and 2015 in the French Hospital Database on HIV. The Andersen and Gill model was used to calculate the adjusted hazard ratios (HRs), focusing on heavy alcohol use and neutrophil function-altering comorbidities. RESULTS: Of 25 795 participants, 1414 developed 1883 severe bacterial infections. Between 2006 and 2009 and 2013 and 2015, the incidence fell from 13.2 (95% confidence interval [CI], 12.3-14.1) to 7.1 (95% CI, 6.3-7.8) per 1000 person-years. Heavy alcohol use was associated with an increased risk of severe bacterial infection (HR = 1.3, 95% CI = 1.1-1.7 for 40-80 g/day and HR = 1.6, 95% CI = 1.2-2.1 for >80 g/day), as were diabetes, chronic kidney disease, and end-stage liver disease (HR = 1.2, 95% CI = 1.0-1.4 when 1 comorbidity; HR = 2.3, 95% CI = 1.6-3.4 when more than 1 comorbidity), and nonacquired immune deficiency syndrome-defining malignancy (HR = 2.0; 95% CI, 1.6-2.4). CONCLUSIONS: Heavy alcohol use was associated with an increased risk of severe bacterial infection, as were neutrophil function-altering comorbidities. Controlled-drinking approaches should be promoted and comorbidity management should be strengthened in PWH.

Daily or on-demand oral tenofovir disoproxil fumarate/emtricitabine for HIV pre-exposure prophylaxis: experience from a hospital-based clinic in France.

BACKGROUND: On-demand oral tenofovir disoproxil fumarate and emtricitabine (TDF/FTC) has been approved for pre-exposure prophylaxis (PrEP) in MSM in France following the results of clinical studies, but data are limited on real-world experience. DESIGN: A single-center, open-label, prospective cohort study that recruited people at high risk of HIV infection in Paris. METHODS: Participants were enrolled in a single hospital-based outpatient clinic and were proposed to start PrEP with daily or on demand TDF/FTC. At baseline and every 3 months thereafter, patients were tested for HIV and creatinine plasma levels, and data on sexual behavior, other sexually transmitted infections (STIs), and tolerability were collected. RESULTS: From 10 November 2015 to 30 April 2017, 1069 patients were screened and 1049 (98.1%) started PrEP. Median age was 36 years, 99.4% were MSM with a median number of partners of 10, and 793 (75.6%) opted for on demand PrEP. Over 486 person-years of follow-up, four HIV-infections were diagnosed in poorly or nonadherent patients (incidence 0.82/100 person-years). Rate of condomless sex at last intercourse increased from 53.3% at baseline to 79% at month 12 (P < 10), but increase in bacterial STI rates was modest (14.6% at baseline vs. 19.2% at month 12; P < 10). Most adverse events were gastrointestinal and did not lead to PrEP discontinuation. CONCLUSIONS: Most PrEP users were high-risk MSM and opted for on-demand PrEP. PrEP use was associated with a low HIV incidence and a high rate of condomless sex with a modest increase in bacterial STIs.

The ANRS-Ipergay trial, an opportunity to use qualitative research to understand the perception of the "participant"-physician relationship.

The ANRS-IPERGAY trial consisted in providing sexual activity-based antiretroviral prophylaxis for HIV prevention (PrEP) with a package of prevention tools (counselling, condoms, HIV and sexually transmitted infections' screening) to highly exposed HIV-negative men who have sex with men (MSM). Few data exist concerning the patient-physician relationship in the particular context of PrEP, where physicians discuss sexual behaviours with MSM who are not classic patients, in that consultation is for prevention purposes, not for illness. This study took place during the open-label extension of ANRS-IPERGAY trial when all participants received PrEP. In this qualitative study, we examined how physicians perceived their relationship with participants in the ANRS-IPERGAY trial. Of all 30 physicians involved in the trial who were contacted by email to participate in an interview about their opinions and perceptions of ANRS-IPERGAY 18 volunteered to participate in the current sub-study. We performed a vertical analysis for each interview to identify the extract in each physician's discourse concerning their relationship with MSM participants, and conducted a horizontal analysis to construct the thematic tree and subsequently investigate differences and similitudes between themes. An analysis of all physicians' discourses showed that the participant-physician relationship during the trial could be described through 4 themes: (i) personal experience of the relationship, (ii) trust and non-judgement, (iii) positive relational climate and (iv) influence of physician's characteristics (age, gender, etc.) on relationship. We found that the particular context of PrEP led some physicians to adopt a patient-as-partner approach during consultations rather than a paternalist or hierarchical approach. Indeed, the close follow-up provided by the trial and the active role of patients in their own prevention care trajectory, are more compatible with the patient-as-partner approach. The prescription of PrEP may lead to an evolution in patient-physician relationships and may even modify the professional identity of physicians.

Doxycycline Prophylaxis for Bacterial Sexually Transmitted Infections: Promises and Perils.

Despite their high global incidence, sexually transmitted infections (STIs) remain a neglected area of research. Increased rates of STIs have been reported in particular among men who have sex with men (MSM) probably because of the advances in the treatment and prophylaxis of human immunodeficiency virus (HIV) infection with a decrease in condom use. A recent report among MSM showed that the use of postexposure prophylaxis with doxycycline could dramatically reduce the incidence of chlamydia and syphilis but not of gonorrhea. The long-term consequences of this strategy are yet unknown, especially the risk of selection and dissemination of syphilis and chlamydia strains with doxycycline resistance, which has not been reported yet.

SUMOylation of human septins is critical for septin filament bundling and cytokinesis.

Septins are cytoskeletal proteins that assemble into nonpolar filaments. They are critical in diverse cellular functions, acting as scaffolds for protein recruitment and as diffusion barriers for subcellular compartmentalization. Human septins are encoded by 13 different genes and are classified into four groups based on sequence homology (SEPT2, SEPT3, SEPT6, and SEPT7 groups). In yeast, septins were among the first proteins reported to be modified by SUMOylation, a ubiquitin-like posttranslational modification. However, whether human septins could be modified by small ubiquitin-like modifiers (SUMOs) and what roles this modification may have in septin function remains unknown. In this study, we first show that septins from all four human septin groups can be covalently modified by SUMOs. We show in particular that endogenous SEPT7 is constitutively SUMOylated during the cell cycle. We then map SUMOylation sites to the C-terminal domain of septins belonging to the SEPT6 and SEPT7 groups and to the N-terminal domain of septins from the SEPT3 group. We finally demonstrate that expression of non-SUMOylatable septin variants from the SEPT6 and SEPT7 groups leads to aberrant septin bundle formation and defects in cytokinesis after furrow ingression. Altogether, our results demonstrate a pivotal role for SUMOylation in septin filament bundling and cell division.