Real-world effectiveness of pre-exposure prophylaxis in men at high risk of HIV infection in France: a nested case-control study.

BACKGROUND: Pre-exposure prophylaxis (PrEP) has shown high efficacy in clinical trials, but few observational studies have confirmed its effectiveness when prescribed in real life to users with diverse profiles. This study aimed to assess real-world PrEP effectiveness. METHODS: We did a matched, nested case-control study among adult men at high risk of HIV infection between Jan 1, 2016, and June 30, 2020, using data from the French national health data system. Men who were newly diagnosed with HIV infection up to Dec 31, 2020, were individually matched with up to five controls for age, socioeconomic status, place of residence, calendar year, and follow-up duration. PrEP use was characterised on the basis of tenofovir disoproxil fumarate plus emtricitabine dispensing over time. Conditional logistic regression was used to calculate the adjusted odds ratios (ORs) of PrEP use associated with HIV infection. PrEP effectiveness (computed as 1-adjusted OR), was estimated overall, by mode of PrEP use, and by individuals' sociodemographic characteristics. FINDINGS: Among a total of 46 706 individuals, 256 patients with HIV infection were identified and matched with 1213 controls. PrEP users accounted for 29% of cases and 49% of controls. PrEP effectiveness was 60% (95% CI 46 to 71) overall, reaching 93% (84 to 97) for a high amount of PrEP consumption, and 86% (78 to 92) if excluding periods after PrEP discontinuation. PrEP effectiveness was significantly reduced in people younger than 30 years (26% [-21 to 54]) and in those who were socioeconomically deprived (-64% [-392 to 45]), both of which groups showed low amounts of PrEP consumption and high rates of PrEP discontinuation. INTERPRETATION: PrEP effectiveness appears to be lower in real-world conditions than is reported in clinical trials. Strengthening efforts to improve the monitoring of PrEP compliance will be essential to ensure PrEP effectiveness, especially among young and socioeconomically deprived recipients. FUNDING: None.

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.

The Benzodiazepine-Dementia Disorders Link: Current State of Knowledge.

The short-term effects of benzodiazepines on memory are well established and are suspected in the long term. Eleven studies have been published so far concerning benzodiazepine use and the risk of dementia disorders; nine of these studies concluded these drugs have a deleterious effect, one found a protective effect, and one (the most recently published) observed no effect. The positive association found in some studies could be due to a reverse causation bias since the main indications for benzodiazepines (e.g. sleep disorders, anxiety) can also be prodromes of dementia disorders. This bias is less likely for treatments started more than 10 years before the diagnosis. Among others, three mechanisms could underlie the potential influence of benzodiazepines on the development of dementia disorders. First, benzodiazepines can decrease beta-site amyloid precursor protein-cleaving enzyme 1 (BACE-1) and γ-secretase activity and slow down the accumulation of Aß oligomers in the brain. This potential positive effect has never been confirmed; the same is true for the prevention of excitotoxicity through benzodiazepine anti-glutamatergic action. Second, since astrocytes located in the area of amyloid plaques could have gamma-aminobutyric acid (GABA)-secreting activity, patients with pre-dementia lesions could be at increased risk of presenting with more pronounced deleterious cognitive effects of benzodiazepines. Finally, owing to the neural compensation and cognitive reserve concepts, some subjects could cope with initial lesions by using/developing alternative networks. By lowering the brain activation level, benzodiazepines could limit this capacity. In conclusion, it is essential that animal studies explore the mechanistic hypotheses of this association found by most of the pharmacoepidemiological studies conducted on this topic.