Journal Article Accepted manuscript Mixing of tecovirimat in water to support oral dosing of children with mpox Get access Zixuan Wei, Zixuan Wei Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, CO, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Kristina M Brooks, Kristina M Brooks Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, CO, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Sharon Nachman, Sharon Nachman Division of Pediatric Infectious Diseases, Stony Brook Children's Hospital, Stony Brook, NY, USA Alternative Corresponding Author: Sharon Nachman, MD, Department of Pediatrics, Renaissance School of Medicine, State University of New York at Stony Brook, 101 Nicholls Road, Stony Brook, NY 11794-8111, [email protected], Phone: 631-444-7692 https://orcid.org/0000-0002-3419-9471 Search for other works by this author on: Oxford Academic PubMed Google Scholar Grace Aldrovandi, Grace Aldrovandi Division of Infectious Diseases, Department of Pediatrics, David Geffen School of Medicine at UCLA, Los Angeles, CA https://orcid.org/0000-0003-1604-9637 Search for other works by this author on: Oxford Academic PubMed Google Scholar Timothy Wilkin, Timothy Wilkin Department of Medicine, Weill Cornell Medical College, Ithaca, NY, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar William Fischer, William Fischer University of North Carolina School of Medicine, Chapel Hill, NC, USA https://orcid.org/0000-0002-4900-098X Search for other works by this author on: Oxford Academic PubMed Google Scholar Jennifer J Kiser, Jennifer J Kiser Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, CO, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Jason Zucker, Jason Zucker Columbia University, New York, NY, USA Corresponding Author: Jason Zucker, MD, MS, Division of Infectious Diseases, Columbia University Irving Medical Center, 622 West 168th Street 8th Floor, New York, NY 10032, [email protected], Phone: 201-723-6637, Fax: 212-305-7290 https://orcid.org/0000-0001-6987-6412 Search for other works by this author on: Oxford Academic PubMed Google Scholar A5418 Study Team A5418 Study Team Search for other works by this author on: Oxford Academic PubMed Google Scholar Journal of the Pediatric Infectious Diseases Society, piaf014, https://doi.org/10.1093/jpids/piaf014 Published: 15 February 2025 Article history Received: 27 November 2024 Published: 15 February 2025
Abstract Background Pregnant people with coronavirus disease 2019 (COVID-19) experience higher risk for severe disease and adverse pregnancy outcomes, but no pharmacokinetic (PK) data exist to support dosing of COVID-19 therapeutics during pregnancy. We report PK and safety data for intravenous remdesivir in pregnancy. Methods IMPAACT 2032 was a phase 4 prospective, open-label, nonrandomized opportunistic study of hospitalized pregnant and nonpregnant women receiving intravenous remdesivir as part of clinical care. Intensive PK sampling was performed on infusion days 3, 4, or 5 with collection of plasma and peripheral blood mononuclear cells (PBMCs). Safety data were recorded from first infusion through 4 weeks after last infusion and at delivery. Geometric mean ratios (GMR) (90% confidence intervals [CI]) of PK parameters between pregnant and nonpregnant women were calculated. Results Fifty-three participants initiated remdesivir (25 pregnant; median gestational age, 27.6 weeks; interquartile range, 24.9–31.0 weeks). Plasma exposures of remdesivir, its 2 major metabolites (GS-704277 and GS-441524), and the free remdesivir fraction were similar between pregnant and nonpregnant participants. Concentrations of the active triphosphate (GS-443902) in PBMCs increased 2.04-fold (90% CI, 1.35–3.03) with each additional infusion in nonpregnant versus pregnant participants. Three adverse events in nonpregnant participants were related to treatment (1 grade 3; 2 grade 2 resulting in treatment discontinuation). There were no treatment-related adverse pregnancy outcomes or congenital anomalies detected. Conclusions Plasma remdesivir PK parameters were comparable between pregnant and nonpregnant women, and no safety concerns were identified based on our limited data. These findings suggest no dose adjustments are indicated for intravenous remdesivir during pregnancy. Clinical Trials Registration NCT04582266.
The impact of human immunodeficiency virus (HIV) infection on children continues to be felt worldwide. Since 1981, when the first patients with HIV were recognized, to 1996, when it was estimated that more than 14 million men, women and children were infected with the virus, no other infectious disease has had such a strong impact on the medical community. With the advent of better methods of detection and better therapies we are beginning to see HIV-infected children surviving longer, and thus coming under the care of a host of affiliated medical personnel, including dentists. This article will serve as a brief update on pediatric HIV and its impact on the oral health of infected children.
Abstract To breast feed or not has long been a difficult question for women with human immunodeficiency virus (HIV) in high-income countries, as undetectable HIV in maternal plasma does not translate to zero risk of transmission while breastfeeding, and clean water and formula are readily available. Recent, and more permissive, changes in US and other high-income-country guidelines regarding breastfeeding underscore this issue and acknowledge the information gaps that are essential for informed maternal choice and provider management. These include lack of guidance as to routine monitoring of mothers during lactation, type and length of prophylaxis for infants, and lack of data on factors associated with increased breast-milk viral load and risk of transmission. Ancillary to data are the education and staffing needs for providers participating in the management of breastfeeding individuals. Future studies of breast-milk transmission will need to evaluate these gaps so that we can move transmission to zero.
Abstract Background A 2-dose mRNA-1273 primary series in children aged 6 months–5 years (25 µg) and 6–11 years (50 µg) had an acceptable safety profile and was immunogenic in the phase 2/3 KidCOVE study. We present data from KidCOVE participants who received an mRNA-1273 booster dose. Methods An mRNA-1273 booster dose (10 µg for children aged 6 months–5 years; 25 µg for children aged 6–11 years; age groups based on participant age at enrollment) was administered ≥6 months after primary series completion. The primary safety objective was the safety and reactogenicity of an mRNA-1273 booster dose. The primary immunogenicity objective was to infer efficacy of an mRNA-1273 booster dose by establishing noninferiority of neutralizing antibody (nAb) responses after a booster in children versus nAb responses observed after the mRNA-1273 primary series in young adults (18–25 years) from the pivotal efficacy study. Data were collected from March 2022 to June 2023. Results Overall, 153 (6 months–5 years) and 2519 (6–11 years) participants received an mRNA-1273 booster dose (median age at receipt of booster: 2 and 10 years, respectively). The booster dose safety profile was generally consistent with that of the primary series in children; no new safety concerns were identified. An mRNA-1273 booster dose elicited robust nAb responses against ancestral SARS-CoV-2 among children and met prespecified noninferiority success criteria versus responses observed after the primary series in young adults. Conclusions Safety and immunogenicity data support administration of an mRNA-1273 booster dose in children aged 6 months to 11 years. Clinical Trials Registration NCT04796896 (Clinicaltrials.gov).
