Willingness-to-use and preferences for model-informed antenatal doses: a cross-sectional study among European healthcare practitioners and pregnant women

Background: Physiological changes in pregnancy may affect drug safety and efficacy, sometimes requiring dose adjustments. Pregnancy-adjusted doses, however, are missing for most medications. Increasingly, pharmacokinetic models can be used for antenatal dose finding. Given the novelty of this technique and questions regarding dose credibility, the acceptability of model-informed antenatal doses should be explored. // Objective: We aimed to assess the willingness-to-use and preferred features for model-informed antenatal doses among healthcare practitioners (HCPs) and pregnant women in European countries. // Methods: A cross-sectional, web-based study drawing on two open surveys was performed between 8 September and 30 November 2022. Each survey comprised statements drawn from prior focus groups, associated with Likert-scales. Themes included respondents’ information needs, search behaviours along with their willingness-to-use and preferred features for model-informed antenatal doses. The surveys were disseminated through professional societies, pregnancy websites and social media. A descriptive analysis was performed. // Results: In total, 608 HCPs from different specialties and 794 pregnant women across 15 countries participated, with 81% of respondents across both groups in the Netherlands or Belgium. Among pregnant women, 31% were medical professionals and 85% used medication during pregnancy. Eighty-three percent of HCPs found current antenatal pharmacotherapy suboptimal and 97% believed that model-informed antenatal doses would enhance the quality of antenatal care. Most HCPs (93%) and pregnant women (75%) would be willing to follow model-informed antenatal doses. Most HCPs desired access to the evidence (88%), including from pharmacokinetic modelling (62%). Most pregnant women (96%) wanted to understand antenatal dosing rationales and to be involved in dosing decisions (97%). // Conclusion: The willingness-to-use model-informed antenatal doses is high among HCPs and pregnant women provided that certain information needs are met

Oral abstracts of the 21st International AIDS Conference 18-22 July 2016, Durban, South Africa

The rate at which HIV-1 infected individuals progress to AIDS is highly variable and impacted by T cell immunity. CD8 T cell inhibitory molecules are up-regulated in HIV-1 infection and associate with immune dysfunction. We evaluated participants (n=122) recruited to the SPARTAC randomised clinical trial to determine whether CD8 T cell exhaustion markers PD-1, Lag-3 and Tim-3 were associated with immune activation and disease progression.Expression of PD-1, Tim-3, Lag-3 and CD38 on CD8 T cells from the closest pre-therapy time-point to seroconversion was measured by flow cytometry, and correlated with surrogate markers of HIV-1 disease (HIV-1 plasma viral load (pVL) and CD4 T cell count) and the trial endpoint (time to CD4 count <350 cells/μl or initiation of antiretroviral therapy). To explore the functional significance of these markers, co-expression of Eomes, T-bet and CD39 was assessed.Expression of PD-1 on CD8 and CD38 CD8 T cells correlated with pVL and CD4 count at baseline, and predicted time to the trial endpoint. Lag-3 expression was associated with pVL but not CD4 count. For all exhaustion markers, expression of CD38 on CD8 T cells increased the strength of associations. In Cox models, progression to the trial endpoint was most marked for PD-1/CD38 co-expressing cells, with evidence for a stronger effect within 12 weeks from confirmed diagnosis of PHI. The effect of PD-1 and Lag-3 expression on CD8 T cells retained statistical significance in Cox proportional hazards models including antiretroviral therapy and CD4 count, but not pVL as co-variants.Expression of ‘exhaustion’ or ‘immune checkpoint’ markers in early HIV-1 infection is associated with clinical progression and is impacted by immune activation and the duration of infection. New markers to identify exhausted T cells and novel interventions to reverse exhaustion may inform the development of novel immunotherapeutic approaches

Striving for balance in decisions on antenatal pharmacotherapy

Most individuals use medication during pregnancy. However, decision making on antenatal pharmacotherapy presents considerable ethical and scientific challenges. Amid a sociocultural paradigm prioritising the elimination of fetal risks, available evidence and guidance are limited, and current decision making on antenatal drugs mostly proceeds in an ad-hoc and, often, biased manner. This approach might undermine the health of both mother and child. The need for a systematic approach towards antenatal drug decisions is becoming even more pressing with the growing knowledge of pregnancy-induced changes in drug disposition and effects. With this new complexity, pregnancy-specific doses might be necessary, potentially altering the balance between maternal and fetal benefits and risks. In this Viewpoint, we argue that ethical principles and a pregnant individual's values must be integrated alongside existing evidence when making decisions on antenatal drug use and dosing. We use the example of sertraline to outline practical strategies for achieving this goal. This approach is urgently needed to foster better-informed and balanced decisions on antenatal pharmacotherapy