No abstract

The HIV-1 virion infectivity factor (Vif) is required during viral replication to inactivate the host cell anti-viral factor, APOBEC3G (A3G). Vif binds A3G and a Cullin5-ElonginBC E3 ubiquitin ligase complex which results in the proteasomal degradation of A3G. The Vif PPLP motif (amino acids 161-164) is essential for normal Vif function because mutations in this motif reduce the infectivity of virions produced in T-cells. In this report, we demonstrate that mutation of the Vif PPLP motif reduces Vif binding to A3G without affecting its interaction with ElonginC and Cullin5. We demonstrate that the failure of the Vif mutant to bind A3G resulted in A3G incorporation into assembling virions with loss of viral infectivity.

Background Hepatitis B (HBV) is prevalent in certain US populations and regular HBV disease monitoring is critical to reducing associated morbidity and mortality. Adherence to established HBV monitoring guidelines among primary care providers is unknown. Aims To evaluate HBV disease monitoring patterns and factors associated with adherence to HBV management guidelines in the primary care setting. Methods Primary providers within the San Francisco safety net healthcare system were surveyed for HBV management practices, knowledge, attitudes, and barriers to HBV care. Medical records from 1,727 HBV-infected patients were also reviewed retrospectively. Results Of 148 (45%) responding providers, 79% reported ALT and 44% reported HBV viral load testing every 6–12 months. Most providers were knowledgeable about HBV but 43% were unfamiliar with HBV management guidelines. Patient characteristics included: mean age 51 years; 54% male; 67% Asian. Within the past year, 75% had ALT; 24% viral load; 21% HBeAg tested, and 40% of at-risk patients had abdominal imaging for HCC. Provider familiarity with guidelines (OR 1.02, 95%CI 1.00–1.03), Asian patient race (OR 4.18, 95%CI 2.40–7.27), and patient age were associated with recommended HBV monitoring. Provider HBV knowledge and attitudes were positively associated, while provider age and perceived barriers were negatively associated with HCC surveillance. Conclusions Comprehensive HBV disease monitoring including HCC screening with imaging were suboptimal. While familiarity with AASLD guidelines and patient factors were associated with HBV monitoring, only provider and practice factors were associated with HCC surveillance. These findings highlight the importance of targeted provider education to improve HBV care.

Goals To evaluate provider knowledge, attitudes and barriers to HBV care and management practices across diverse primary care settings. Background Factors influencing adherence to recommended hepatitis B virus (HBV) screening and management guidelines are poorly defined. Methods Providers across various healthcare settings in San Francisco were surveyed. Multivariate analyses were used to identify factors associated with recommended HBV screening, vaccination, and disease monitoring. Results Of 277 (41.3%) responding providers, 42% reported performing HBV screening in >50% of at-risk patients, and 49%, HBV vaccination in >50% of eligible patients. Most reported appropriate monitoring of a majority of HBV-infected patients with ALT (79%) and HBV viral load (67%) every 6–12 months, but performed any hepatocellular carcinoma (HCC) screening in 49%. Provider factors significantly associated with HBV screening were speaking an Asian language (OR 3.27), offering HBV treatment (OR 3.00), having >25% of Asian patients in practice (OR 2.10), practicing in safety net settings (OR 7.51) and having higher barrier score (OR 0.74). Appropriate HBV monitoring was associated with provider speaking an Asian language (OR 3.43) and provider age (OR 0.68/decade). HCC screening was associated with having >25% of patients speaking English as a second language (OR 4.26) and practicing in safety net settings (OR 0.14). Conclusions Rates of adherence to HBV guidelines were suboptimal irrespective of practice setting and were influenced by certain provider, patient and practice factors. This study reinforces the importance of engaging primary care providers in development, dissemination, and implementation of evidence-based HBV practice guidelines.

BACKGROUND: Hepatitis B (HBV) represents a significant health disparity among medically underserved Asian and Hawaiian/Pacific Islander (API) populations. Studies evaluating adherence to HBV screening and vaccination guidelines in this population are limited. OBJECTIVE: The purpose of this study was to evaluate HBV screening and vaccination practices using both provider self-report and patient records. DESIGN: Medical records for 20,574 API adults were reviewed retrospectively and primary care providers were surveyed to evaluate rates and adherence to HBV screening and vaccination guidelines. PARTICIPANTS: The study included primary care providers and their adult API patients in the San Francisco safety-net healthcare system. MAIN MEASURES: Patient, practice, and provider factors, as well as HBV screening and vaccination practices, were assessed using provider survey constructs and patient laboratory and clinical data. Generalized linear mixed models and multivariate logistic regression analyses were used to identify factors associated with recommended HBV screening and vaccination. KEY RESULTS: The mean age of patients was 52 years, and 63.4 % of patients were female. Only 61.5 % underwent HBV testing, and 47.4 % of HBV-susceptible patients were vaccinated. Of 148 (44.8 %) responding providers, most were knowledgeable and had a favorable attitude towards screening, but 43.2 % were unfamiliar with HBV guidelines. HBV screening was positively associated with favorable provider attitude score (OR per unit 1.80, 95 % CI 1.18-2.74) and negatively associated with female patient sex (OR 0.82, 95 % CI 0.73-0.92), a higher number of clinic patients per week (OR per 20 patients 0.46, 95 % CI 0.28-0.76), and provider barrier score (OR per unit 0.45, 95 % CI 0.24-0.87). HBV vaccination was negatively associated with provider barrier score (OR per unit 0.48, 95 % CI 0.25-0.91). CONCLUSIONS:Rates of HBV screening and vaccination of API patients in this safety-net system are suboptimal, and provider factors play a significant role. Efforts to cultivate positive attitudes among providers and expand healthcare system resources to reduce provider barriers to HBV care are warranted. 1 Asian and Hawaiian/Pacific Islanders (API) represent a particularly high-risk population, with reported prevalence rates of 10-15 %, and are estimated to account for over 40 % of chronic HBV cases in the U.S. 2HBV is associated with increased morbidity and mortality; 15-40 % of patients will develop cirrhosis, liver failure, or hepatocellular carcinoma (HCC).3 The recent U.S. Institute of Medicine report highlights the need for increasing efforts in the United States to screen for, prevent, and treat HBV infection. 4 To meet this goal, it is imperative that we have a better understanding of the complex interplay between patient, provider, and health system factors limiting preventive care and progress towards HBV eradication. whose parents are from regions of high HBV endemicity, and persons with high-risk behaviors, among others. 1,5 While the 2004...