Leveraging interdisciplinary management in people with HIV and lymphoid neoplasms.

BACKGROUND: Drug-drug interactions between antiretroviral treatment (ART) and cytostatics may have a negative impact in the prognosis of people with HIV (PWH) and cancer. OBJECTIVE: The objective of this study is to evaluate the impact of the implementation of interdisciplinary management and the type of ART in PWH diagnosed with lymphoid neoplasms. METHODS: This is a multicentric, retrospective observational cohort study including PWH diagnosed with lymphoid neoplasm who started first-line chemotherapy between 2008 and 2020. Demographic, clinical and therapeutic variables were obtained from the electronic medical records and associated with 5-year progression-free survival (PFS) and overall survival (OS) using Cox proportional hazard models. RESULTS: A total of 118 individuals were included. Boosted ART was being used in 55 (46.6%) cases at the time of neoplasm diagnosis. The Infectious Diseases or the Pharmacy Department was consulted before starting chemotherapy in 79/118 (66.9%) cases. Interdisciplinary management resulted in fewer subjects taking boosted ART (17.7% versus 71.8%, P < 0.001) and more subjects using unboosted integrase strand transfer inhibitor-based ART (74.7% versus 7.7%, P < 0.001). The use of boosted ART with chemotherapy was associated with worse 5-year PFS (P = 0.003) and 5-year OS (P = 0.016). There was a trend towards better 5-year PFS and OS when interdisciplinary management was implemented, with significant differences for individuals receiving boosted ART at neoplasm diagnosis (P = 0.0246 and P = 0.0329, respectively). CONCLUSIONS: Our findings underscore the significant impact of the type of ART on the prognosis of PWH undergoing chemotherapy. Encouraging collaborative management between oncologists, pharmacists and HIV teams for these patients enhances PFS and OS rates.

Outcomes of Drug Interactions Between Antiretrovirals and Co-Medications, Including Over-the-Counter Drugs: A Real-World Study.

INTRODUCTION: The objective was to characterize real-world outcomes of drug-drug interactions (DDIs) between antiretrovirals (ARVs) and other drugs, including over-the-counter medications (OTC), and treatment outcomes in clinical practice. METHODS: www.clinicalcasesDDIs.com is an open-access website for healthcare providers to consult and briefly describe real-world clinical cases on DDI with ARVs. We reviewed all the clinical cases reported to the website between March 2019 and May 2023. RESULTS: A total of 139 cases were reported, mostly involving ritonavir or cobicistat (boosters; 74 cases), unboosted integrase inhibitors (InSTI; 29 cases), and non-nucleoside reverse transcriptase inhibitors (NNRTI; 23 cases). Central nervous system drugs (29 cases) and cardiovascular drugs (19 cases) were the most frequently described co-medications. Notably, OTC medications were implicated in 27 cases, including mineral supplements (11 cases), herbals (8 cases), weight loss drugs (4 cases), anabolic steroids (3 cases), and recreational drugs (1 case). OTC acted as the perpetrator drug in 21 cases, leading to loss of ARV efficacy in 17 instances (mineral supplements in 10 cases, weight loss drugs in 4 cases, herbals in 3 cases). Additionally, toxicity was reported in 4 out of 6 cases where OTC was considered the victim drug of the DDI (anabolic steroids in 3 cases, MDMA in 1 case). CONCLUSIONS: Frequent unwanted outcomes resulting from DDIs between ARVs and OTC medications underscore the importance of integrating non-prescription drugs into medication reconciliation. The real-world data available through www.clinicalcasesDDIs.com serves as a valuable resource for assessing the clinical relevance of DDIs.

Immune responses associated with mpox viral clearance in men with and without HIV in Spain: a multisite, observational, prospective cohort study.

BACKGROUND: Since the emergence of the global mpox outbreak in May, 2022, more than 90 000 cases have been diagnosed across 110 countries, disproportionately affecting people with HIV. The durability of mpox-specific immunity is unclear and reinfections have been reported. We aimed to compare mpox immune responses up to 6 months after diagnosis in participants with and without HIV and assess their effect on disease severity and viral clearance dynamics. METHODS: This study was embedded within a prospective, observational, multicentre cohort study of viral clearance dynamics among people with mpox in Spain (MoViE). We included women and men aged 18 years or older, who had signs of mpox, and reported having symptom onset within the previous 10 days at the moment of mpox diagnosis from three sex clinics of the Barcelona metropolitan area. Samples from skin ulcers were collected weekly to estimate the time to clear monkeypox virus (MPXV) from skin lesions. Blood samples were taken at diagnosis, 29, 91, and 182 days later for immune analysis. This included quantifying IgG and IgA against three mpox antigens by ELISA, evaluating in-vitro neutralisation, and characterising mpox-specific T-cell responses using interferon γ detecting enzyme-linked immunospot (ELISpot) assay and multiparametric flow cytometry. FINDINGS: Of the 77 originally enrolled participants, we included 33 participants recruited between July 19, and Oct 6, 2022. Participants without HIV (19 [58%] participants) and participants with HIV (14 [42%] participants) had similar clinical severity and time to MPXV clearance in skin lesions. Participants with HIV had a CD4+ T-cell count median of 777 cells per µL (IQR 484-1533), and 11 (78%) of 14 were virally suppressed on antiretroviral therapy. Nine (27%) of 33 participants were age 49 years or older. 15 (45%) of 33 participants were originally from Spain, and all participants were men. Early humoral responses, particularly concentrations and breadth of IgG and IgA, were associated with milder disease and faster viral clearance. Orthopoxvirus-specific T cells count was also positively correlated with MPXV clearance. Antibody titres declined more rapidly in participants with HIV, but T-cell responses against MPXV were sustained up to day 182 after diagnosis, regardless of HIV status. INTERPRETATION: Higher breadth and magnitude of B-cell and T-cell responses are important in facilitating local viral clearance, limiting mpox dissemination, and reducing disease severity in individuals with preserved immune system. Antibodies appear to contribute to early viral control and T-cell responses are sustained over time, which might contribute to milder presentations during reinfection. FUNDING: Fundació Lluita contra les Infeccions, IrsiCaixa, and Consorcio Centro de Investigación Biomédica en Red, Instituto de Salud Carlos III, Ministerio de Ciencia, Innovación e Universidades.

Immunogenicity, reactogenicity, and safety of a second booster with BNT162b2 or full-dose mRNA-1273: A randomized VACCELERATE trial in adults aged ≥75 years (EU-COVAT-1-AGED Part B).

OBJECTIVES: To assess the safety and immunogenicity of a fourth vaccination (second booster) in individuals aged ≥75 years. METHODS: Participants were randomized to BNT162b2 (Comirnaty, 30 µg) or messenger RNA (mRNA)-1273 (Spikevax, 100 µg). The primary end point was the rate of two-fold antibody titer increase 14 days after vaccination, targeting the receptor binding domain (RBD) region of wild-type SARS-CoV-2. The secondary end points included changes in neutralizing activity against wild-type and 25 variants. Safety was assessed by monitoring solicited adverse events (AEs) for 7 days. RESULTS: A total of 269 participants (mean age 81 years, mRNA-1273 n = 135/BNT162b2 n = 134) were included. Two-fold anti-RBD immunoglobulin (Ig) G titer increase was achieved by 101 of 129 (78%) and 116 of 133 (87%) subjects in the BNT162b2 and the mRNA-1273 group, respectively (P = 0.054). A second booster of mRNA-1273 provided higher anti-RBD IgG geometric mean titer: 21.326 IU/mL (95% confidence interval: 18.235-24.940) vs BNT162b2: 15.181 IU/mL (95% confidence interval: 13.172-17.497). A higher neutralizing activity was noted for the mRNA-1273 group. The most frequent AE was pain at the injection site (51% in mRNA-1273 and 48% in BNT162b2). Participants in the mRNA-1273 group had less vaccine-related AEs (30% vs 39%). CONCLUSIONS: A second booster of either BNT162b2 or mRNA-1273 provided substantial IgG increase. Full-dose mRNA-1273 provided higher IgG levels and neutralizing capacity against SARS-CoV-2, with similar safety profile for subjects of advanced age.

Infarto talámico bilateral por compromiso de la arteria de percheron / Bilateral Thalamic Infarct by Commitment of the Artery of Percheron

Introduccion: La arteria de Percheron se origina de un solo tronco arterial talamoperforante que proporciona suministro bilateral a los tálamos paramedianos y al mesencéfalo rostral. Esta es una variante anatómica que permite la irrigación bilateral de los tálamos, a partir de un tronco común de origen asimétrico en la arteria cerebral posterior. Las lesiones en esta área dan origen a una variedad de manifestaciones clínicas. Caso clínico: Presentamos el caso de una paciente femenina blanca de 89 años, quien fue admitida en el Hospital Virgen de los Lirios de Alcoy, diagnosticada con Infarto talámico bilateral de la arteria de Percherón. Discusión: Son muchos los factores por el cual este infarto es infradiagnosticado, entre ellos, la baja estimación de la frecuencia de este infarto junto con la gran heterogeneidad clínica y además la baja sensibilidad de la Tomografía computarizada en la fase hiperaguda. En general el pronóstico a largo plazo es bueno, este varía con respecto a los patrones radiológicos encontrados, siendo más afectados los casos en los que involucra mesencefalo...(AU)