Clinical Infectious Diseases最新文献

This article provides a focused update to the clinical practice guideline on the treatment and management of patients with coronavirus disease 2019, developed by the Infectious Diseases Society of America. The guideline panel presents a recommendation on the use of the anti-severe acute respiratory syndrome coronavirus 2 neutralizing antibody pemivibart as pre-exposure prophylaxis. The recommendation is based on evidence derived from a systematic review and adheres to a standardized methodology for rating the certainty of evidence and strength of recommendation according to the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach. Information on pemivibart is included in the U.S. Food and Drug Administration Emergency Use Authorization for this agent.

Introduction: The equity-focused ILANA study evaluated feasibility, acceptability, appropriateness of delivering on-label two-monthly cabotegravir and rilpivirine (CAB+RPV) injections for HIV-1 therapy in clinics and community settings.

Methods: The study, which mandated inclusive recruitment, was conducted May-December 2022 at six UK sites. Injections were delivered in clinic (months 1-6), and in clinic or community setting according to patient choice (months 6-12). Surveys were completed at baseline, M4 and M12 using validated measures for feasibility (FIM), acceptability (AIM), and appropriateness (IAM). Primary endpoint: proportion of participants agreeing that the injection and community setting were feasible (FIM>4) at M12. Fourteen participants completed interviews at baseline and M12.

Results: Community settings offered by sites included: home visits (n=3), HIV support organisations (n=2), community clinic (n=1). Of 114 participants,54% were female, 70% racially minoritised and 40% aged >50. 27/114 chose to receive injections in community settings. FIM/AIM/IAM scores at M12 were high for the injection (79.0-87.4%) and lower for the community setting (44.2-47.4%) overall. Subgroup analyses indicated differences in scores by gender and ethnicity. Among those who attended the community, FIM/AIM/IAM scores for the community setting at M12 were high (73.1-80.8%). Concerns about stigma, inconvenience, and losing access to trusted clinicians negatively influenced perceptions of receiving injections at community settings, amongst other factors.

Conclusion: CAB+RPV injections were considered highly feasible, acceptable, and appropriate, however few chose community delivery. Those that chose community delivery found it highly acceptable and feasible. Further exploration of CAB+RPV delivery in alternative community sites not offered (e.g. primary care or pharmacies) is warranted.

Background: Influenza A results in significant morbidity and mortality. VIR-2482, an engineered human monoclonal antibody with extended half-life, targets a highly conserved epitope on the stem region of influenza A hemagglutinin and may protect against seasonal and pandemic influenza.

Methods: This double-blind, randomized, placebo-controlled, phase 2 study examined the safety and efficacy of VIR-2482 for seasonal influenza A illness prevention in unvaccinated healthy adults. Participants (N = 2977) were randomized 1:1:1 to receive VIR-2482 450 mg, VIR-2482 1200 mg, or placebo via intramuscular injection. Primary and secondary efficacy endpoints were the proportions of participants with reverse transcriptase-polymerase chain reaction-confirmed influenza A infection and either protocol-defined influenza-like illness (ILI) and Centers for Disease Control and Prevention-defined ILI or World Health Organization-defined ILI, respectively.

Results: VIR-2482 450 mg and 1200 mg prophylaxis did not reduce the risk of protocol-defined ILI with reverse transcriptase-polymerase chain reaction-confirmed influenza A versus placebo (relative risk reduction, 3.8% [95% confidence interval (CI), -67.3 to 44.6] and 15.9% [95% CI, -49.3 to 52.3], respectively). At the 1200-mg dose, the relative risk reductions in influenza A illness were 57.2% (95% CI: -2.5 to 82.2) using Centers for Disease Control and Prevention ILI and 44.1% (95% CI: -50.5 to 79.3) using World Health Organization ILI definitions, respectively. Serum VIR-2482 levels were similar regardless of influenza status; variants with reduced VIR-2482 susceptibility were not detected. Local injection site reactions were mild and similar across groups.

Conclusions: VIR-2482 1200 mg intramuscular was well tolerated but did not significantly prevent protocol-defined ILI. Secondary endpoint analyses suggest this dose may have reduced influenza A illness. Trial registration: ClinicalTrials.gov identifier, NCT05567783.