Development, Implementation, and Scale Up of the National Furaha Yangu Campaign to Promote HIV Test and Treat Services Uptake Among Men in Tanzania.

Evidence has demonstrated that immediate HIV treatment initiation upon a positive HIV test, referred to as Test and Treat, can help people living with HIV live longer, healthier lives and prevent HIV transmission. Although Tanzania adopted the evidence-based Test and Treat strategy since 2016, men were not being adequately reached for HIV services. A national campaign was launched to promote the new HIV services with a focus on men. To inform the development and implementation of the campaign, we conducted formative audience insights-gathering (AIG) sessions to assess facilitators and barriers to accessing HIV Test and Treat services and inform the concepts and materials for the campaign. Qualitative AIG interviews and focus group discussions were conducted with 54 people who were unaware or aware of their HIV status and currently or not currently on treatment, as well as health workers. Facilitators and barriers included a fear of testing positive, the desire to belong, control their narratives, and reinvent themselves to achieve their dreams and live a happy life. The campaign played off a My Happiness! creative concept to position antiretroviral therapy (ART) as a solution to fears around what life would be like after a positive HIV diagnosis. The development and implementation of the campaign were informed by the AIG sessions and national stakeholders, leading to strong partners' buy-in that supported the scale-up of the ongoing campaign from 12 to 26 regions via the collaborative efforts of government, donors, and implementing partners.

A phase II study of Mirvetuximab Soravtansine in triple-negative breast cancer.

Folate receptor alpha (FRα) has been reported to be expressed in up to 80% of triple-negative breast cancers (TNBC) with limited expression in normal tissues, making it a promising therapeutic target. Mirvetuximab soravtansine (mirvetuximab-s) is an antibody drug conjugate which has shown promise in the treatment of FRα-positive solid tumors in early phase clinical trials. Herein, are the results of the first prospective phase II trial evaluating mirvetuximab-s in metastatic TNBC. Patients with advanced, FRα-positive TNBC were enrolled on this study. Mirvetuximab-s was administered at a dose of 6.0 mg/kg every 3 weeks. 96 patients with advanced TNBC consented for screening. FRα staining was performed on tumor tissue obtained from 80 patients. The rate of FRα positivity by immunohistochemistry was 10.0% (8/80). Two patients were treated on study, with best overall responses of stable disease in one and progressive disease in the other. Adverse events were consistent with earlier studies. The study was terminated early due to the low rate of FRα positivity in the screened patient population and lack of disease response in the two patients treated. The observed rate of FRα positivity was considerably lower than previously reported and none of the patients had a partial or complete response. Treatment with mirvetuximab-s should only be further explored in TNBC if an alternate biomarker strategy is developed for patient selection on the basis of additional preclinical data.

Discovery of VX-509 (Decernotinib): A Potent and Selective Janus Kinase 3 Inhibitor for the Treatment of Autoimmune Diseases.

While several therapeutic options exist, the need for more effective, safe, and convenient treatment for a variety of autoimmune diseases persists. Targeting the Janus tyrosine kinases (JAKs), which play essential roles in cell signaling responses and can contribute to aberrant immune function associated with disease, has emerged as a novel and attractive approach for the development of new autoimmune disease therapies. We screened our compound library against JAK3, a key signaling kinase in immune cells, and identified multiple scaffolds showing good inhibitory activity for this kinase. A particular scaffold of interest, the 1H-pyrrolo[2,3-b]pyridine series (7-azaindoles), was selected for further optimization in part on the basis of binding affinity (Ki) as well as on the basis of cellular potency. Optimization of this chemical series led to the identification of VX-509 (decernotinib), a novel, potent, and selective JAK3 inhibitor, which demonstrates good efficacy in vivo in the rat host versus graft model (HvG). On the basis of these findings, it appears that VX-509 offers potential for the treatment of a variety of autoimmune diseases.