Division of Infectious Diseases and Environmental Medicine Copyright (c) 2013 Thomas Jefferson University All rights reserved. http://jdc.jefferson.edu/didem Recent documents in Division of Infectious Diseases and Environmental Medicine en-us Fri, 22 Feb 2013 16:41:08 PST 3600 A novel codon insert in protease of clade B HIV type 1. http://jdc.jefferson.edu/didem/3 http://jdc.jefferson.edu/didem/3 Tue, 27 Mar 2012 11:51:00 PDT A novel combination of three codon inserts in the pol coding region of HIV-1 RNA was identified in a highly antiretroviral experienced study subject with HIV-1 infection. A one codon insert was observed in the protease region between codon 40 and 41 simultaneously with a two codon insert present in the reverse transcriptase region at codon 69.

]]> Parris S Jordan et al. Base Sequence HIV Infections HIV Protease HIV Reverse Transcriptase HIV-1 Humans Models, Molecular Molecular Sequence Data Mutagenesis, Insertional RNA, Viral Sequence Analysis, DNA Recruitment and retention of diverse populations in antiretroviral clinical trials: practical applications from the gender, race and clinical experience study. http://jdc.jefferson.edu/didem/2 http://jdc.jefferson.edu/didem/2 Thu, 22 Mar 2012 12:29:11 PDT BACKGROUND: Women, particularly women of color, remain underrepresented in antiretroviral (ARV) clinical trials. To evaluate sex-based differences in darunavir/ritonavir-based therapy, the Gender, Race And Clinical Experience (GRACE) study was designed to enroll and retain a high proportion of women representative of the racial/ethnic demographics of women with HIV/AIDS in the United States. The recruitment and retention strategies used in GRACE are described in this article.

METHODS: Recruitment and retention strategies targeting women included selecting study sites that focused on women, involving community consultants, site-specific enrollment plans, access to other ARV drugs, study branding, site and patient toolkits, targeted public relations, site grants for patient support, and subsidized child care and transportation.

RESULTS: The recruitment strategies were successful; 287 (67%) women were enrolled, primarily women of color (black, n=191 [67%], Hispanic, n=60 [21%]). Despite the focus on retention, a greater proportion of women (32.8%) discontinued compared with men (23.2%).

CONCLUSIONS: The successes of GRACE in enrolling a representative population of women were rooted in pretrial preparation, engagement of community advisors, enrollment quotas, choice of study sites and site support. Lessons learned from GRACE may be applied to future study design. Further focus on factors that influence discontinuation is warranted.

]]> Ron Falcon et al. Adult Anti-HIV Agents Attitude to Health Clinical Trials as Topic Ethnic Groups Female HIV Infections Humans Middle Aged Patient Acceptance of Health Care Patient Selection Research Subjects Vulnerable Populations Young Adult Enhanced neutralization potency of botulinum neurotoxin antibodies using a red blood cell-targeting fusion protein. http://jdc.jefferson.edu/didem/1 http://jdc.jefferson.edu/didem/1 Wed, 14 Mar 2012 13:51:14 PDT Botulinum neurotoxin (BoNT) potently inhibits cholinergic signaling at the neuromuscular junction. The ideal countermeasures for BoNT exposure are monoclonal antibodies or BoNT antisera, which form BoNT-containing immune complexes that are rapidly cleared from the general circulation. Clearance of opsonized toxins may involve complement receptor-mediated immunoadherence to red blood cells (RBC) in primates or to platelets in rodents. Methods of enhancing immunoadherence of BoNT-specific antibodies may increase their potency in vivo. We designed a novel fusion protein (FP) to link biotinylated molecules to glycophorin A (GPA) on the RBC surface. The FP consists of an scFv specific for murine GPA fused to streptavidin. FP:mAb:BoNT complexes bound specifically to the RBC surface in vitro. In a mouse model of BoNT neutralization, the FP increased the potency of single and double antibody combinations in BoNT neutralization. A combination of two antibodies with the FP gave complete neutralization of 5,000 LD50 BoNT in mice. Neutralization in vivo was dependent on biotinylation of both antibodies and correlated with a reduction of plasma BoNT levels. In a post-exposure model of intoxication, FP:mAb complexes gave complete protection from a lethal BoNT/A1 dose when administered within 2 hours of toxin exposure. In a pre-exposure prophylaxis model, mice were fully protected for 72 hours following administration of the FP:mAb complex. These results demonstrate that RBC-targeted immunoadherence through the FP is a potent enhancer of BoNT neutralization by antibodies in vivo.

]]> Sharad P Adekar et al. Animals Antibodies, Monoclonal Antibodies, Neutralizing Biotinylation Botulinum Toxins, Type A Erythrocytes Female Injections Mice Neutralization Tests Protein Binding Recombinant Fusion Proteins