Gilead Sciences (United Kingdom)

A focus group organised by the Drug Safety Research Unit (DSRU) International Working Group (IWG) on New Developments in Pharmacovigilance discussed current challenges and opportunities in pharmacovigilance (PV), emphasising the need for a multimodal approach in data analysis and accessibility of diverse data sources for drug safety surveillance. Nine participants, selected purposefully for their multisectoral expertise in PV, discussed the value of various data types, including data from clinical trials and real-world data (RWD), each offering distinct strengths and limitations. Key challenges identified included data standardisation, quality variability, technological barriers and ethical concerns, particularly with data derived from social media. Emerging tools such as knowledge graphs were highlighted for their potential to enhance data integration and signal detection, however further research is required. The group also addressed disparities in data access, with particular attention to regulatory restrictions, limited infrastructure in low-resource settings and restricted access to industry-held data. Proposed solutions included fostering greater data transparency, establishing secure data-sharing platforms and forming collaborative consortia to facilitate responsible and ethical data use. Overall, the discussion underscored the need for improved integration, access and methodological rigour to strengthen PV practices and enhance global drug safety monitoring.

Abstract Background Maintaining virologic suppression through antiretroviral treatment (ART) is essential for optimizing the health outcomes of people living with HIV (PWH) and reducing transmission risk. Virologic suppression requires strict adherence to ART regimens. Many PWH find oral regimen adherence to be challenging; however, text reminders are a potential tool that can support adherence. To determine if implementation of text reminders from healthcare providers supported adherence, viral suppression, and patient satisfaction, we implemented a customizable SMS-based medication text reminder service offered to individuals receiving HIV care in order determine impact. Methods Patients (≥18 years, PWH) at Boston Medical Center were enrolled in the texting service by clinical staff from 02/19/22 to 03/08/24 (N=47). Participants could fully customize the timing, content, and language of their reminders. Demographic and viral load (VL) data were extracted from the medical record, including baseline VL before enrollment and most recent VL as of 09/30/24 or closest to service disenrollment. McNemar’s test was used to assess association between VL suppression and exposure to the texting service (N=37). Virologic suppression was defined as < 200 copies/mL. Perceived adherence and satisfaction were assessed through optional text surveys among participants enrolled ≥30 days (N=21); four also completed follow-up phone interviews. Results Table 1 shows the N=37 individuals enrolled in the text message service with baseline demographics. Median baseline VL was 188 copies/mL with 49% (N=18) unsuppressed at baseline (Table 2). We found a statistically significant difference between pre- and post-intervention VL suppression for patients who enrolled in the reminder service (p=0.0003). Results were also significant among the same patients using a 50 copies/mL threshold (p=0.0019). Survey respondents self-reported improved or maintained medication adherence levels and high satisfaction (Table 3). Conclusion Results suggest the implementation of customizable care team-delivered text medication reminders can be used as a tool to achieve virologic suppression, ART adherence, and continued patient satisfaction. Disclosures Melanie Berry, PharmD, Gilead: Smpliyee Michael Maiullari, PharmD, BCIDP, Gilead Sciences: Advisor/Consultant|ViiV Healthcare: Advisor/Consultant Archana Asundi, MD, DayZero Diagnostics: Grant/Research Support|Gilead Sciences: Advisor/Consultant|Gilead Sciences: Grant/Research Support|Theratechnologies: Grant/Research Support|Viiv Healthcare: Grant/Research Support

BackgroundThe treatment landscape for COVID-19 has evolved rapidly since the virus emerged in 2019. Immunocompromised, older and/or frail patients with COVID-19 are at higher risk of severe disease or death than the general population. This retrospective study examined treatment patterns in adults hospitalized with COVID-19 in the US from 12/1/2021 to 06/30/2024.Figure 1:A Sankey Plot illustrating the treatment pathways experienced by immunocompromised hospitalised patients with COVID-19MethodsUsing linked claims and chargemaster data, adults hospitalized with COVID-19 and >6 months of baseline healthcare insurance enrolment were selected. Corticosteroids (CS), remdesivir (RDV), Janus kinase inhibitor (JAKi), interleukin-6 inhibitors (IL-6i), nirmatrelvir plus ritonavir, and molnupiravir use were assessed from admission until death, discharge/transfer, 28 days after admission, or end of data. Therapies initiated prior to admission were not counted. Key subgroups were defined by age, diagnosis codes, and a published frailty algorithm.ResultsThe main cohort included 73,555 patients (mean age 59 years; 44% male). Most (59%) patients did not receive any COVID-19 treatments. The most common first-regimen treatments were CS alone (23%), CS/RDV combination (12%), and RDV alone (4%). Second regimen and third regimen treatments were identified in 13% (9,483) and 5% (3,984) of patients, respectively.Among the 27,355 immunocompromised patients included (Figure 1), 58% had no treatments of interest. The most common initial treatment regimens were CS alone (21%), CS/RDV combination (13%), and RDV alone (5%). Second regimens were observed in 12% of immunocompromised patients; 5% had a third regimen treatment.In patients without RDV-contraindicated conditions, RDV was used by 22% (3,765/16,775) of immunocompromised patients and 27% (4,928/18,316) of patients aged >65 during the assessment period. In patients aged >65, RDV was more commonly used in robust patients (28%), compared to mildly frail (24%) and moderate/severely frail (23%) patients.ConclusionMany patients hospitalised with COVID-19 did not receive any COVID-19 indicated treatments. Less than 1 in 5 immunocompromised patients received RDV, indicating a potential treatment unmet need. Frail older patients were less likely to receive RDV than robust patients; further research is needed in this area.DisclosuresHarriet Dickinson, PhD, Gilead Sciences: Employment|Gilead Sciences: Stocks/Bonds (Public Company) Mark Berry, PhD, Gilead Sciences, Inc.: Employee|Gilead Sciences, Inc.: Stocks/Bonds (Public Company) Amanda Kong, DrPH, Aetion: Employee|Aetion: Stocks/Bonds (Private Company) Alice Bersani, Masters, Aetion: Employment|Aetion: Stocks/Bonds (Private Company)|Boehringer ingelheim: Employment Isabella Lelis, BA, Aetion: Employment Anand Chokkalingam, PhD, Gilead Sciences: Employment|Gilead Sciences: Stocks/Bonds (Public Company)

Peripheral helper T (Tph) cells, a recently identified Th cell subset, have been implicated in various autoimmune diseases. However, their role in granulomatosis with polyangiitis (GPA) remains unclear. This study aimed to investigate the potential clinical significance of circulating Tph cells (cTph) in GPA. Peripheral blood mononuclear cells were collected from 74 remission GPA-patients, 26 active GPA-patients and 22 age- and sex-matched healthy controls. Flow cytometry was used to quantify cTph cells and their subset distribution. Single-cell multi-omics profiling was performed in an independent cohort (5 remission GPA-patients, 5 active GPA-patients and 5 healthy controls). Plasma IL-21 levels were measured by enzyme-linked immunosorbent assay, and associations between cTph cells and clinical parameters were evaluated. active GPA-patients showed an increased frequency and absolute number of cTph compared to remission GPA-patients, and both GPA groups exhibited cTph2-skewed distribution compared to healthy controls. Remission GPA-patients with generalized disease exhibited higher cTph frequencies than those with localized disease. cTph cells from active GPA-patients displayed an activated phenotype and a transcriptional profile marked by pro-inflammatory and survival-associated genes. Plasma IL-21 levels did not differ significantly between the three groups. Notably, absolute counts of memory cTph and cTph2 cells correlated positively with clinical markers of disease activity, and were significantly elevated in GPA patients with higher cytoplasmic antineutrophil cytoplasmic antibody (c-ANCA) titers. cTph cells are expanded and exhibit an activated, pro-inflammatory profile with a cTph2-skewed distribution in active GPA-patients. Their association with disease activity may support a potential role in disease pathogenesis and highlight their potential as therapeutic targets, warranting further investigation.

BICSTaR is a multinational, prospective, observational study that aimed to evaluate bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) in HIV treatment-naïve (TN) and treatment-experienced (TE) participants in routine clinical practice. Month 12 analysis of the French cohort with respect to virologic effectiveness, drug-related adverse events (DRAEs), emergence of resistance, body weight, and patient-reported outcomes using the HIV Symptom Index and the HIV Treatment Satisfaction Questionnaire. A total of 240 participants initiated B/F/TAF in January-July 2019 (56 TN, 184 TE), 79% of whom were male, with a median age of 50 years. At baseline, 63% (TN: 46%, TE: 68%) presented with comorbidities. At month 12, HIV-1 RNA was <50 cp/mL in 92% (43/47) of TN and 96% (134 of 139) of TE in missing = excluded analysis (discontinuation = failure analysis: TN: 92% [43 of 47], TE: 92% [134 of 146]). No major mutations associated with B/F/TAF resistance emerged. A total of 7% (16 of 240) discontinued B/F/TAF, including 4% (10 of 240) due to DRAEs and none for virologic reasons. DRAEs were reported in 13% (30 of 240) (no renal DRAE). The median changes in body weight were +6.5 kg in TN and +1.0 kg in TE. The number of bothersome symptoms decreased in the TN group, and treatment satisfaction significantly increased in the TE group. These French real-world data confirm the effectiveness, safety, and tolerability of B/F/TAF in TN and TE participants with a high prevalence of comorbidities.