Noninferior Immunogenicity and Consistent Safety of Respiratory Syncytial Virus Prefusion F Protein Vaccine in Adults 50-59 Years Compared to ≥60 Years of Age.

BACKGROUND: The adjuvanted respiratory syncytial virus (RSV) prefusion F protein-based vaccine (RSVPreF3 OA) is approved in adults aged ≥60 years. We evaluated RSVPreF3 OA immunogenicity and safety in adults aged 50-59 years without or with increased risk for RSV disease due to specific chronic medical conditions. METHODS: This observer-blind, phase 3, noninferiority trial included adults aged 50-59 years, stratified into 2 subcohorts: those with and those without predefined, stable, chronic medical conditions leading to an increased risk for RSV disease. Participants in both subcohorts were randomized 2:1 to receive RSVPreF3 OA or placebo. A control group of adults aged ≥60 years received RSVPreF3 OA. Primary outcomes were RSV-A and RSV-B neutralization titers (geometric mean titer ratios and sero-response rate differences) 1 month post-vaccination in 50-59-year-olds versus ≥60-year-olds. Cell-mediated immunity and safety were also assessed. RESULTS: The exposed population included 1152 participants aged 50-59 years and 381 participants aged ≥60 years. RSVPreF3 OA was immunologically noninferior in 50-59-year-olds versus ≥60-year-olds; noninferiority criteria were met for RSV-A and RSV-B neutralization titers in those with and those without increased risk for RSV disease. Frequencies of RSVPreF3-specific polyfunctional CD4+ T cells increased substantially from pre- to 1 month post-vaccination. Most solicited adverse events had mild-to-moderate intensity and were transient. Unsolicited and serious adverse event rates were similar in all groups. CONCLUSIONS: RSVPreF3 OA was immunologically noninferior in 50-59-year-olds compared to ≥60-year-olds, in whom efficacy was previously demonstrated. The safety profile in 50-59-year-olds was consistent with that in ≥60-year-olds. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov: NCT05590403.

Long-term safety and impact of immune recovery in heavily treatment-experienced adults receiving fostemsavir for up to 5 years in the phase 3 BRIGHTE study.

Introduction: Fostemsavir is a gp120-directed attachment inhibitor approved for heavily treatment-experienced (HTE) adults with multidrug-resistant HIV-1. We provide detailed week 240 safety results from the BRIGHTE study and evaluate the impact of immune recovery on safety outcomes. Methods: The phase 3 BRIGHTE trial is ongoing; data for this analysis were collected from the first participant's first visit (February 23, 2015) through the last participant's last visit for week 240 (March 22, 2021). Safety endpoints were assessed in participants who received fostemsavir + optimized background therapy. In participants with baseline CD4+ T-cell count <200 cells/mm3, exposure-adjusted adverse event (AE) rates were assessed among subgroups with or without CD4+ T-cell count ≥200 cells/mm3 at any time during 48-week analysis periods through week 192. Results: Through a median of 258 weeks (range, 0.14-319) of treatment, discontinuations due to AEs occurred in 30/371 (8%) participants. Serious AEs were reported in 177/371 (48%) participants, including 16 drug-related events in 13 (4%) participants. Thirty-five (9%) deaths occurred, primarily related to AIDS or acute infections. COVID-19-related events occurred in 25 (7%) participants; all resolved without sequelae. Among participants with baseline CD4+ T-cell count <200 cells/mm3, 122/162 (75%) achieved CD4+ T-cell count ≥200 cells/mm3 at week 192. Exposure-adjusted AE rates were markedly lower among participants achieving CD4+ T-cell count ≥200 cells/mm3 at any time vs those sustaining <200 cells/mm3. No new AIDS-defining events were reported after week 48 in participants with CD4+ T-cell count ≥200 cells/mm3. Conclusions: Cumulative safety findings through the BRIGHTE 240-week interim analysis are consistent with other trials in HTE participants with advanced HIV-1 and comorbid disease. Reduced rates of AIDS-defining events and AEs were observed in participants with immunologic recovery on fostemsavir-based treatment. Clinical trial number: NCT02362503, https://clinicaltrials.gov/study/NCT02362503.

Evaluación del impacto de la pandemia de COVID-19 en el seguimiento y tratamiento de gestantes con sífilis y sus parejas: análisis comparativo con un período prepandémico / Evaluation of the impact of the COVID-19 pandemic onthe follow-up and treatment of pregnant women with syphilis and their partners: comparative analysis with a pre-pandemic period

Se realizó un estudio observacional descriptivo transver-sal retrospectivo de las gestantes con nuevo diagnóstico de sífilis atendidas en el Hospital Materno Infantil de San Isidro "Dr. Carlos Gianantonio" durante los años pandé-micos 2020-2021. Se asistieron 108 gestantes con sífilis: 69 en 2020 y 39 en 2021. El tratamiento de aquellas que finalizaron el embarazo al momento de realizar este estu-dio (n=95) fue adecuado en el 78% (74) de los casos, en el 16,8% (16) fue inadecuado y el 5,2 % (5) perdió el segui-miento. El 11% presentó reinfección durante el embarazo. Con respecto a las parejas (n=103), el 84,6% (88) tenía una relación estable; se testeó al 70% (73) de las parejas, de las cuales el 45% (33) tenía VDRL positiva y se trató al 88% (29). Los resultados del estudio no muestran diferencias significativas en los indicadores evaluados (tratamiento adecuado y reinfección de la gestante y testeo/tratamien-to de la pareja) al comparar los períodos prepandémico (2018-2019) vs. pandémico (2020-2021)

A retrospective cross-sectional descriptive observational study of pregnant women with a new diagnosis of syphilis treated at the San Isidro Maternity Hospital during the 2020-2021 pandemic years was carried out. 108 pregnant women with syphilis were assisted: 69 in 2020 and 39 in 2021. The treatment of those who ended their pregnancy at the time of this study (n=95) was adequate in 78% (74) of the cases, 16,8% (16) were inadequate and 5.2% (5) lost follow-up. 11% presented reinfection during pregnancy. Regarding the couples (n=103), 84.6% (88) had a stable relationship, 70% (73) of the couples were tested, of which 45% (33) had positive vdrl and were treated 88% (29). The results of the study do not show significant differences in the indicators evaluated (adequate treatment and reinfection of the pregnant woman and testing/treatment of the partner) when comparing the pre-pandemic (2018-2019) vs. pandemic (2020-2021) periods

Cohorte de gestantes y puérperas con COVID-19. Análisis comparativo entre dos olas pandémicas / Cohort of pregnant and postpartum women with COVID-19. Comparative analysis between two pandemic waves

Resumen Introducción: La presentación clínica de las gestantes con COVID-19 fue variando según el momento de la pandemia. Objetivo: Se describió la clínica, complicaciones y letalidad, así como un análisis comparativo de la presentación clínica durante las dos primeras olas pandémicas de las gestantes y puérperas con COVID-19. Métodos: Se realizó un estudio de cohorte prospectivo observacional de las gestantes asistidas en la Maternidad Municipal de San Isidro entre el 01/04/2020 al 31/07/21. Resultados: Se confirmó la infección de 103 gestantes, de las cuales el 76.7% cursó un cuadro leve, 18.4% moderado y 4.8% grave. El 59% fueron asistidas por telemedicina, el 41% se internó, de las cuales el 2.9% requirieron asistencia respira toria mecánica (ARM). La mayoría tuvo buena evolución y la tasa de letalidad fue <1% (n = 1). Al momento del presente análisis el 78% de las mujeres habían finalizado la gestación. El 41% de ellas, presentó algún tipo de complicación, siendo lo más frecuente: ruptura prematura de membrana 42%, hipertensión arterial y otras pato logías asociadas (incluyendo una paciente con preeclampsia) el 27% y parto pretérmino el 18%. En el análisis comparativo entre las dos primeras olas pandémicas, hubo una mayor proporción de casos moderados/graves (p=0.016) y fue significativamente mayor la indicación de ARM (p=0.048) en el 2021. Discusión: Estos hallazgos avalan la necesidad de priorizar a este grupo de pacientes para implementar estrategias preventivas.

Abstract Introduction: The clinical presentation of pregnant women with COVID-19 varied according to the time of the pandemic. Objective: The clinic, complications and lethality were described, as well as a comparative analy sis of the clinical presentation during the first two pandemic waves of pregnant and postpartum women with COVID-19. Methods: An observational prospective cohort study of pregnant women assisted in the Municipal Maternity of San Isidro was carried out between 04/01/2020 and 07/31/21. Results: The infection was confirmed in 103 pregnant women, 76.7% had a mild condition, 18.4% moderate and 4.8% severe. 59% were assisted by telemedicine, 41% were admitted and 2.9% required mechanical ventilation. Most had a good evolution and the case fatality rate was < 1% (n = 1). At the time of this analysis, 78% of the women had completed pregnancy. 41% of them presented some type of complication, the most frequent being: premature rupture of the membrane 42%, arterial hypertension and other associated pathologies (including a patient with preeclampsia) 27% and preterm delivery 18%. In the comparative analysis between the first two pandemic waves, there was a higher proportion of moderate/severe cases (p = 0.016) and the indication for mechanical ventilation was significantly higher (p = 0.048) in 2021. Discussion: These findings support the need for prioritize this group of patients to implement preventive strategies