Factors Associated with PrEP Persistence and Loss of Follow-Up: A 5-Year Historic Cohort.

OBJECTIVE: HIV Pre-Exposure Prophylaxis (PrEP) has been used in France since 2016. Its effectiveness is no longer to be demonstrated. However, follow-up and adherence remain the main pitfalls. The main objective of this study was to identify factors associated with persistence or loss of PrEP follow-up. DESIGN: An historic cohort of PrEP users was compiled from the database of consultations in the Indre-et-Loire dedicated sexual health centers (CeGIDD) from June 2016 to June 2021. METHODS: Kaplan-Meier curves were performed to compare the group of persistent PrEP users to the discontinuation group. Factors associated with PrEP discontinuation were identified using Cox modelling, considering time-dependent variables. Final variables included in the model were selected based on the Akaike Information Criterion (AIC) and clinical relevance. RESULTS: Over the period, 568 PrEP users were included in the cohort. Median follow-up was 2.3 years. A quarter of users were lost to follow-up within 3 months after PrEP initiation. Sexual risk reduction AIDS community-based support (HR = 0.65[0.42;0.99]), being in a couple (HR = 0.51[0.38;0.68]), and history of syphilis (HR = 0.57[0.40;0.81]) were significantly associated with persistence of follow-up. Remote consultations (HR = 2.74[1.63;4.61]), chemsex practices (HR = 2.01[1.29;3.14]), and side effects (HR=1.72[1.03;2.88]) were significantly associated with a loss of follow-up. CONCLUSION: These results suggest that more sexual risk reduction AIDS community-based counseling could be a key, necessary for supporting PrEP users in their follow-up pathway. Indeed, AIDS community-based support could be used to build a basis for developing safe pathways. Remote consultations could represent a response to the issue of access to PrEP. To create a significant impact on global HIV incidence, the PrEP offer must be extended, and at-risk PrEP users supported to maintain PrEP use.

Performance of French medico-administrative databases in epidemiology of infectious diseases: a scoping review.

The development of medico-administrative databases over the last few decades has led to an evolution and to a significant production of epidemiological studies on infectious diseases based on retrospective medical data and consumption of care. This new form of epidemiological research faces numerous methodological challenges, among which the assessment of the validity of targeting algorithm. We conducted a scoping review of studies that undertook an estimation of the completeness and validity of French medico-administrative databases for infectious disease epidemiological research. Nineteen validation studies and nine capture-recapture studies were identified. These studies covered 20 infectious diseases and were mostly based on the evaluation of hospital claimed data. The evaluation of their methodological qualities highlighted the difficulties associated with these types of research, particularly those linked to the assessment of their underlying hypotheses. We recall several recommendations relating to the problems addressed, which should contribute to the quality of future evaluation studies based on medico-administrative data and consequently to the quality of the epidemiological indicators produced from these information systems.

Quantitative analysis of the formation of nucleoprotein complexes between HIV-1 Gag protein and genomic RNA using transmission electron microscopy.

In HIV, the polyprotein precursor Gag orchestrates the formation of the viral capsid. In the current view of this viral assembly, Gag forms low-order oligomers that bind to the viral genomic RNA triggering the formation of high-ordered ribonucleoprotein complexes. However, this assembly model was established using biochemical or imaging methods that do not describe the cellular location hosting Gag-gRNA complex nor distinguish gRNA packaging in single particles. Here, we studied the intracellular localization of these complexes by electron microscopy and monitored the distances between the two partners by morphometric analysis of gold beads specifically labeling Gag and gRNA. We found that formation of these viral clusters occurred shortly after the nuclear export of the gRNA. During their transport to the plasma membrane, the distance between Gag and gRNA decreases together with an increase of gRNA packaging. Point mutations in the zinc finger patterns of the nucleocapsid domain of Gag caused an increase in the distance between Gag and gRNA as well as a sharp decrease of gRNA packaged into virions. Finally, we show that removal of stem loop 1 of the 5'-untranslated region does not interfere with gRNA packaging, whereas combined with the removal of stem loop 3 is sufficient to decrease but not abolish Gag-gRNA cluster formation and gRNA packaging. In conclusion, this morphometric analysis of Gag-gRNA cluster formation sheds new light on HIV-1 assembly that can be used to describe at nanoscale resolution other viral assembly steps involving RNA or protein-protein interactions.

PrEP monitoring and HIV incidence after PrEP initiation in France: 2016-18 nationwide cohort study.

BACKGROUND: Clinical trials have demonstrated that oral pre-exposure prophylaxis (PrEP) has high efficacy in preventing HIV transmission. In many countries, HIV testing is recommended prior to PrEP initiation, 1 month after and quarterly thereafter. We assessed the uptake of HIV testing and estimated the incidence of HIV infections after oral PrEP initiation, by using the French national health database (SNDS). METHODS: A historic cohort study included every adult person who started oral PrEP between 1 January 2016 and 30 June 2018 in France. HIV infection was tracked in the follow-up, from first PrEP dispensation up to 31 December 2018. Factors associated with adherence to HIV testing in PrEP follow-up were analysed using a generalized linear mixed model. RESULTS: PrEP users (9893) were followed for a median duration of 551 days (IQR 350-769). The first HIV test, 1 month after PrEP initiation, was performed by 64% of users. For subsequent tests, this rate exceeded 81% and remained stable over time. HIV testing was lower among PrEP users without prescription refill (OR 0.15; 99% CI 0.12-0.20), but higher if the last prescription was made by a hospital practitioner (OR 2.03; 99% CI 1.69-2.45). Twenty-nine HIV infections were identified, leading to an incidence of 0.19 cases per 100 person-years (99% CI 0.12-0.30). CONCLUSIONS: We confirmed good adherence to HIV testing and efficacy of PrEP in users, which should help in decreasing HIV incidence in France. This study also revealed that SNDS could be a powerful automated tool for the epidemiological monitoring of PrEP users.