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Uptake of pre-exposure prophylaxis (PrEP) has dramatically increased but remains well below the estimated number of individuals who could benefit from PrEP in the United States, and uptake remains limited among young men who have sex with men (YMSM) and MSM of color. Reasons for not adopting PrEP as a prevention strategy among those at elevated risk for HIV is an important area of inquiry that could advise efforts to better position PrEP as an active part of prevention programs. As part of a mixed methods study investigating experiences with repeat HIV testing, we identified main themes emerging from in-depth interview data pertaining to reasons why YMSM report not using PrEP, among YMSM with frequent access to HIV testing services. Themes from 14 in-depth interviews with predominantly Latino MSM for not using PrEP included perceived burden of daily dosing, feeling that risk was not high enough to warrant PrEP, and beliefs that PrEP would have severe adverse events affecting the kidneys and bones. Less prominent but noteworthy themes included stigma as a PrEP user, social or provider influence on decisions not to use PrEP, and preference for current prevention strategy. No differences in PrEP discourse were noted across those at different levels of HIV risk. Results suggest that efforts are needed to engage communities and individuals around PrEP-related education, facilitate risk evaluation, and reduce PrEP stigma. New formulations and nondaily regimens may also be of particular interest to YMSM who may perceive daily PrEP regimens as highly burdensome.

Author(s): Felner, Jennifer K; Mittal, Maria L; Hoenigl, Martin; Amico, K Rivet; Grelotti, David J; Eanes, Alex; Hess, Kristen; Crawford, Jessica; Smith, Laramie R | Abstract: IntroductionTo end the HIV epidemic, HIV prevention and pre-exposure prophylaxis (PrEP) promotion efforts must reach young men who have sex with men (YMSM) at greatest risk for HIV. This study qualitatively explored whether common metrics used by clinicians, scientists, and public health officials to objectively assess HIV risk align with how YMSM conceptualize their risk for HIV and the factors that shape YMSM's risk perceptions.MethodsInterviews with a racially/ethnically diverse sample of HIV-negative YMSM (ages 19-24 years, 60% Latinx; n = 20) examined conceptualizations of HIV risk within the context of repeat HIV testing. Iterative, applied thematic analysis examined how participants conceptualized and constructed their HIV risk, and compared participants' descriptions of their risk with a validated quantitative assessment of HIV risk that reliably predicts HIV seroconversion in this group.ResultsObjective quantitative assessments of HIV risk poorly aligned with participants' perceived HIV risk. Participants described their current risk in relative terms (relative to past risk and relative to friends'/peers' risk) and described age/developmental stage and changes in knowledge about HIV prevention as key factors in risk changes over time. Other factors included substance use and trust/mistrust in sexual partners and scientific advances in HIV prevention (eg, U = U and PrEP). Factors that influenced participants' perceived HIV risk were similar regardless of objective risk assessment.ConclusionsQuantitative assessments of risk may poorly align with risk perception among YMSM. Although objective metrics can effectively target YMSM at greatest risk for HIV transmission, interventions to improve prevention behaviors and PrEP uptake may be more effective when tailored to bridge the disconnection between objective HIV risk assessments and YMSM's constructions of risk.

Objectives (1) To identify factors that influence child feeding practices and beliefs among Hispanic mothers in a low-income community; (2) to describe the use of social media, other internet websites, and text messaging among Hispanic mothers; and (3) to explore mothers' perceptions of social media and/or text messaging interventions to prevent childhood obesity. Methods Mixed methods descriptive study with a sequential explanatory design. Hispanic mothers (N = 66) from Detroit, Michigan with children between 6 and 36 months of age completed surveys regarding their child feeding practices, the source (s) influencing these practices, and their use of social media, internet, and text messaging. During qualitative interviews (N = 19), we explored mothers' use of social media and internet websites to find child health information as well as mothers' perspectives on social media/internet/text messaging interventions to promote child health. Results Most survey respondents were between the ages of 20 and 39 years. One-third of mothers breastfed their child for >6 months; 68% did not introduce solids until their child was older than 6 months. The majority (96%) owned a cellphone; 75% used social media at least once daily. Few mothers indicated that social media and other internet websites influenced their child feeding decisions. During qualitative interviews (N = 19), almost all mothers expressed interest in social media and/or text messaging as a tool to communicate information regarding child health and feeding. Conclusions Hispanic mothers had high rates of social media use and most desired social media/internet/text messaging interventions to promote child health.

Abstract 4670 BACKGROUND: Acute hemolytic reactions (AHR) associated with administration of Rho (D) Immune Globulin (RhIG; WinRho® SDF, Cangene Corporation, Winnipeg, Canada) have been infrequently reported during the previous 16 years. AHR were defined as any case reported with signs of hemolysis (hemoglobin decrease, haptoglobin decrease, LDH increase, elevation of bilirubin, etc.) occurring within hours to a number of days after RhIG administration irrespective of the degree of change from baseline. Intravascular hemolysis (IVH) was defined as a specific type of AHR in which plasma or urinary hemoglobin were positive. The reporting rate of AHR (including IVH) among RhIG-treated patients was previously estimated as 1/946 doses (0.11%), while the estimated reporting rate of IVH was 1/3,271 doses (0.03%).1 Reports surrounding the clinical monitoring of such patients have led to the analysis of AHR post-marketing data. AIMS/PURPOSE: Identify the onset of AHR/IVH symptoms relative to RhIG and determine if prior exposure to RhIG mitigates the risk of such events. METHODS: Retrospective evaluation of AHR (AEs reported with signs of hemolysis; including IVH) from the Cangene post-marketing surveillance database. RESULTS: CONCLUSION: Of the ITP patients who developed IVH, 40% reported an onset of symptoms within 4 hours of RhIG infusion; an additional 10% reported symptoms within 8 hours. The symptom onset was unidentified in 18% of IVH cases. In addition, previous uneventful administration of RhIG did not preclude the possibility of an occurrence of IVH and its complications following subsequent administration of RhIG; however, the majority (approx 84%) of reports of IVH were among RhIG naïve patients. Disclosures: Muller: Cangene: Employment. Little:Cangene: Employment. Hess:Cangene: Employment. Sinclair:Cangene: Employment.

The Ras-Raf-MAPK signaling pathway plays a central role in diverse cellular processes including differentiation, proliferation and survival. This pathway is activated in a large percentage of cancers as a result of mutations in Ras or in B-Raf Ser/Thr kinase. The activating mutation V600E in B-Raf is present in approximately 60% of melanomas and occurs with lower, yet still significant, frequency in human colon and thyroid cancers. Hence, V600EB-Raf has received considerable interest as a small-molecule drug discovery target within the pharmaceutical industry. A high-throughput screen of Amgen's internal kinase preferred library against a recombinant V600EB-Raf kinase domain enzyme identified a class of biarylamide compounds as potent inhibitors of this kinase, and potential starting points for medicinal chemistry efforts. However, these compounds suffered from poor kinase selectivity, particularly against tyrosine kinases from the Src-, VEGFR and PDGFR-families. Crystal structures of representative examples of this scaffold in B-Raf and other tyrosine kinases identified a unique pocket in B-Raf that could be accessed to achieve selective inhibitors of this enzyme. Consequently a novel series of isoquinoline-based compounds was derived which demonstrated potent inhibition against V600EB-Raf enzyme and inhibition of MAPK pathway signaling in cell lines harboring V600EB-Raf. Further optimization within this inhibitor class yielded compounds with favorable in vivo properties as demonstrated by robust inhibition of ERK phosphorylation in V600EB-Raf driven pharmacodynamic models. Crystallographic work supporting the optimization of this series of selective B-Raf inhibitors will be presented. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2681A.