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Ellen Dowers,1 Francis Zamora,1 Lydia Aoun Barakat,2 Onyema Ogbuagu2 1Department of Pharmacy Services, Yale-New Haven Hospital, New Haven, CT, USA; 2Yale AIDS Program, Section of Infectious Diseases, Yale University School of Medicine, New Haven, CT, USA Abstract: Much progress has been made in the development of antiretroviral therapies (ARTs) for HIV-1 infection. Beginning a little over a decade ago, single tablet combination regimens (STRs) became available, and subsequently, newer STR formulations with improved safety profiles have emerged. Recently, there is a growing interest in regimen simplification with the primary goal of further reducing long-term toxicities of ART and improving medication adherence. Dolutegravir/rilpivirine (DTG/RPV) was approved by the US Food and Drug Administration (FDA) as the first dual antiretroviral STR for the maintenance therapy of HIV-1 infection. Following an extensive review of all published papers on RPV and DTG, administered alone and in combination, extracted from databases including PubMed, Google scholar, and EMBASE, as well as drug package inserts and conference abstracts and proceedings, this review discusses the chemical properties and composition, pharmacodynamics and pharmacokinetic properties, clinical trial efficacy and safety data, as well as important drug–drug interactions associated with DTG/RPV. An expert opinion section discusses ideal candidates for DTG/RPV in the context of available but limited data and in comparison to currently available and emerging ART alternatives. Keywords: dolutegravir, rilpivirine, antiretroviral therapy, HIV

ObjectivesOutcomes of community-acquired pneumonia (CAP) among HIV-infected older adults are unclear.MethodsAssociations between HIV infection and three CAP outcomes (30-day mortality, readmission within 30 days post-discharge, and hospital length of stay [LOS]) were examined in the Veterans Aging Cohort Study (VACS) of male Veterans, age ≥ 50 years, hospitalized for CAP from 10/1/2002 through 08/31/2010. Associations between the VACS Index and CAP outcomes were assessed in multivariable models.ResultsAmong 117 557 Veterans (36 922 HIV-infected and 80 635 uninfected), 1203 met our eligibility criteria. The 30-day mortality rate was 5.3%, the mean LOS was 7.3 days, and 13.2% were readmitted within 30 days of discharge. In unadjusted analyses, there were no significant differences between HIV-infected and uninfected participants regarding the three CAP outcomes (P > 0.2). A higher VACS Index was associated with increased 30-day mortality, readmission, and LOS in both HIV-infected and uninfected groups. Generic organ system components of the VACS Index were associated with adverse CAP outcomes; HIV-specific components were not. Among HIV-infected participants, those not on antiretroviral therapy (ART) had a higher 30-day mortality (HR 2.94 [95% CI 1.51, 5.72]; P = 0.002) and a longer LOS (slope 2.69 days [95% CI 0.65, 4.73]; P = 0.008), after accounting for VACS Index. Readmission was not associated with ART use (OR 1.12 [95% CI 0.62, 2.00] P = 0.714).ConclusionAmong HIV-infected and uninfected older adults hospitalized for CAP, organ system components of the VACS Index were associated with adverse CAP outcomes. Among HIV-infected individuals, ART was associated with decreased 30-day mortality and LOS.

Abstract Purpose The goal of this study was to evaluate the relative contribution of treatment intensity, family sociodemographic risk, and family resources to health-related quality of life (QOL) of 102 adolescents in treatment for cancer. Methods Adolescents and parents completed self-report measures of teen QOL, family functioning, and parent-child bonding. Based on parent report of family sociodemographic variables, an additive risk index was computed. A pediatric oncologist rated treatment intensity. Results Simultaneous regression analyses demonstrated the significant contribution of roles in family functioning and quality of parent-child relationship to prediction of psychosocial QOL (parent and teen-reported) as well as parent-reported teen physical QOL over and above the contribution of treatment intensity. Family sociodemographic risk did not contribute to QOL in these regression analyses. In additional analyses, specific diagnosis, types of treatment and individual sociodemographic risk variables were not associated with QOL. Parent and teen ratings of family functioning and quality of life were concordant. Conclusions Family functioning, including quality of parent-child relationship, are central and potentially modifiable resistance factors in teen QOL while under treatment for cancer. Even more important than relying on diagnosis or treatment, screening for roles and relationships early in treatment may be an important aspect of determining risk for poor QOL outcomes.

Abstract Background This study aimed to clarify associations between pain, psychological adjustment, and family functioning with health-related quality of life (HRQOL) in a sample of adolescents with sickle cell disease (SCD) utilizing teen- and parent-report. Methods Forty-two adolescents (between the ages of 12 and 18) with SCD and their primary caregivers completed paper-and-pencil measures of pain, teen's psychological adjustment, and HRQOL. In addition, primary caregivers completed a measure of disease-related parenting stress. Medical file review established disease severity. Results Pearson correlations identified significant inverse associations of pain frequency with physical and psychosocial domains of HRQOL as rated by the teen and primary caregiver. Generally, internalizing symptoms (i.e. anxiety and depression) and disease-related parenting stress were also significantly correlated with lower HRQOL. Examination of possible mediator models via a series of regression analyses confirmed that disease-related parenting stress served as a mediator between pain frequency and physical and psychosocial HRQOL. Less consistent were findings for mediation models involving internalizing symptoms. For these, parent-rated teen depression and teen anxiety served as mediators of the association of pain frequency and HRQOL. Conclusion Results are consistent with extant literature that suggests the association of pain and HRQOL and identify concomitant pain variables of internalizing symptoms and family variables as mediators. Efforts to improve HRQOL should aim to address internalizing symptoms associated with pain as well as parenting stress in the context of SCD management.

Physical activity is associated with improved health outcomes among people with HIV (PWH). In the recent pandemic context, policies designed to mitigate COVID-19 transmission may result in an increase in sedentary lifestyle and decreased physical activity. In this study, we aimed to characterize self-reported physical activity and factors associated with physical inactivity during the first wave of the COVID-19 pandemic among a sample of PWH engaged in care. We also described whether psychological coping strategies measured by the Brief COPE differed based on physical activity levels. Among 260 surveyed PWH in two HIV clinics in the US Northeast, 28.5% (n = 74) met the criteria for being physically active according to the Centers for Disease Control and Prevention (CDC)'s physical activity guidelines. Receiving care in New Haven, CT, presence of a detectable HIV viral load, every day tobacco use, and unhealthy alcohol use were associated with physical inactivity. Problem-focused coping, emotion-focused coping, and avoidance-focused coping strategies were found to be protective against physical inactivity. In adjusted analysis, only problem-focused coping continued to be significantly associated with lower odds of reporting physical inactivity. Efforts are urgently needed to promote physical activity among PWH, including among those without problem-focused coping strategies., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: To end the HIV and hepatitis C virus (HCV) epidemics, people who use drugs (PWUD) need more opportunities for testing. While inpatient hospitalizations are an essential opportunity to test people who use drugs (PWUD) for HIV and HCV, there is limited research on rates of inpatient testing for HIV and HCV among PWUD., Methods: Eleven hospital sites were included in the study. Each site created a cohort of inpatient encounters associated with injection drug use. From these cohorts, we collected data on HCV and HIV testing rates and HIV testing consent policies from 65 276 PWUD hospitalizations., Results: Hospitals had average screening rates of 40% for HIV and 32% for HCV, with widespread heterogeneity in screening rates across facilities. State consent laws and opt-out testing policies were not associated with statistically significant differences in HIV screening rates. On average, hospitals that reflexed HCV viral load testing on HCV antibody testing did not have statistically significant differences in HCV viral load testing rates. We found suboptimal testing rates during inpatient encounters for PWUD. As treatment (HIV) and cure (HCV) are necessary to end these epidemics, we need to prioritize understanding and overcoming barriers to testing., Competing Interests: Potential conflicts of interest. All authors: no reported conflicts., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

The central nervous system HIV reservoir is incompletely understood and is a major barrier to HIV cure. We profiled people with HIV (PWH) and uninfected controls through single-cell transcriptomic and T cell receptor (TCR) sequencing to understand the dynamics of HIV persistence in the CNS. In PWH on ART, we found that most participants had single cells containing HIV-1 RNA, which was found predominantly in CD4 central memory T cells, in both cerebrospinal fluid (CSF) and blood. HIV-1 RNA-containing cells were found more frequently in CSF than blood, indicating a higher burden of reservoir cells in the CNS than blood for some PWH. Most CD4 T cell clones containing infected cells were compartment specific, while some (22%) - including rare clones with members of the clone containing detectable HIV RNA in both blood and CSF - were found in both CSF and blood. These results suggest that infected T cells trafficked between tissue compartments and that maintenance and expansion of infected T cell clones contributed to the CNS reservoir in PWH on ART.

Background: COVID-19 forced a rapid transition to telehealth. Little is known about the use of telephone versus video visits among people living with or at risk for HIV (PWH)., Setting: We studied electronic health record data from an urban HIV clinic. Our sample included visit- and person-level data. Visit-level data came from appointments scheduled from 30 March 2020 to 31 May 2020. Person-level data came from patients 18+ years of age who completed at least one telephone or video visit during the period of interest., Methods: We performed a cross-sectional analysis. Our primary outcome was telehealth modality (telephone or video). We compared visit completion status by telehealth modality. We evaluated associations between patient characteristics and telehealth modality using logistic regression., Results: In total, 1742 visits included information on telehealth modality: 1432 telephone (82%) and 310 (18%) video visits. 77% of telephone visits were completed compared to 75% of video visits ( p  = 0.449). The clinic recorded 643 completed telehealth visits in April and 623 in May 2020. The proportion of telephone visits decreased from 84% in April to 79% in May ( p  = 0.031). Most patients participated in telephone versus video visits (415 vs. 88 patients). Older age (adjusted odds ratio [AOR] 3.28; 95% confidence interval [CI], 1.37-7.82) and Black race (AOR 2.42; 95% CI, 1.20-4.49) were positively associated with telephone visits. Patient portal enrollment (AOR 0.06; 95% CI, 0.02-0.16) was negatively associated with telephone visits., Conclusion: PWH used telephone more than video visits, suggesting that telephone visits are a vital healthcare resource for this population., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

Aims: In this study, novel synthesized 1,6-disubstituted-1-azacoumarin-3-carboxylic acid derivatives were designed, synthesized and evaluated as potential anticancer agents. Materials & methods: The cytotoxicity of novel 1-azacoumarin-3-carboxylic acid derivatives was tested using an MTT assay. High potency was shown by DNA flow cytometry on MCF-7 cells for compound 3b . In addition, topoisomerase IIβ, caspase 3/7, Bax and Bcl-2 enzymes were used to study apoptotic activity. In the same studies, molecular docking analysis assessed activity. Results & conclusion: Cytotoxicity screening identified multiple bioactive compounds, especially compound 3b . Analysis of DNA flow cytometry revealed that compound 3b exhibited cell cycle arrest. Compound 3b had an increase in the expression of Bax/Bcl-2 ratio and caspase 3/7, and a decrease in topoisomerase IIβ enzyme inhibition.

In response to longstanding healthcare inequities unmasked by the Coronavirus Disease 2019 pandemic, the infectious diseases (ID) section at the Yale School of Medicine designed and implemented a pilot curriculum integrating Infectious Disease Diversity, Equity, and Antiracism (ID2EA) into ID educational training and measured program outcomes. We herein describe a mixed-methods assessment of section members on whether the ID2EA curriculum affected their beliefs and behaviors regarding racism and healthcare inequities. Participants rated the curriculum as useful (92% averaging across sessions) and effective in achieving stated learning objectives (89% averaging across sessions), including fostering understanding of how inequities and racism are linked to health disparities and identifying strategies to effectively deal with racism and inequities. Despite limitations in response rates and assessment of longer-term behavioral change, this work demonstrates that training in diversity, equity, and antiracism can be successfully integrated into ID physicians' educational activities and affect physicians' perspectives on these topics., Competing Interests: Potential conflicts of interest. S. E. G. reports that the Yale School of Medicine Department of Internal Medicine awarded an $5000 educational research grant to the ID2EA committee. This award is to expand the curriculum and work of the committee, and none of the funding goes directly to committee members. B. E. reports consulting fees from and participation on data safety monitoring or advisory board for Theratechnologies (treatment-experienced human immunodeficiency virus [HIV] and HIV and liver disease). M. P. G. reports payment or honoraria from Health Monitor Network for contributing to an article (payment to author) and participation as a data safety monitoring board member for Universidade Federal de Minas Gerais (use of methotrexate for treatment of chikungunya arthritis in Brazil). J. P. M. reports grants or contracts to institution from the National Institute on Drug Abuse, National Institute of Mental Health, National Institute of Allergy and Infectious Diseases, and National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, the Substance Abuse and Mental Health Services Administration, the Doris Duke Charitable Foundation, and Gilead Science; consulting fees to author from the National Institute on Drug Abuse; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events to author from the Opioid Response Network, the National Institutes of Health grant review, the Doris Duke Charitable Foundation grant review, University of Massachusetts Worcester, and the New England AIDS Education and Training Center; payment for expert testimony to author from Budge and Heipt, Yale Law School, Munger, Tolles & Olson, LLP, Baltimore CDF, Silver Golub & Teitell, and the Lawyers’ Committee for Civil Rights Under Law (John Fowler). J. R. reports an unpaid role as chair of the Advocacy Committee for the History of Science Society. S. V. S. reports that her spouse worked for Merck Pharmaceuticals from 1997 to 2007 and retains stock in a retirement account (no conflict of interest regarding the current work but included for full disclosure). M. V. reports HRSA-22-028 (HIV and aging Special Projects of National Significance grant) from Yale University and the Connecticut Department of Public Health (Ryan White Part B funding) from Yale–New Haven Hospital; personal consulting fees from ViiV Healthcare, Gilead Sciences, and Janssen Pharmaceuticals; personal payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from the CT AIDS Education and Training Center and Northeast AIDS Education and Training Center; support for attending meetings and/or travel from Yale University for the Conference on Retroviruses and Opportunistic Infections and from the CT State Medical Society for American Medical Association national meetings; noncompensated roles as president of the New Haven County Medical Association, a board member for Project Access New Haven, and a council member for the CT State Medical Society; stock or stock options within retirement funds; and other personal financial or nonfinancial interests in Healthline and Guidepoint. M. S. D. reports roles as president and past president of American Committee of Molecular, Cellular, and Immunoparasitology subgroup of the American Society of Tropical Medicine and Hygiene. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: The study aimed to investigate the over expression of IFITM3 in hepatocellular carcinoma Egyptian patients., Background: Hepatocellular carcinoma (HCC) continues to be a serious disease burden. Interferon Induced Transmembrane protein 3 (IFITM3) is a protein that encoded in humans by the IFITM3 gene. It plays a critical role in the immune system's defense, responsible for a large portion of the antiviral activity. In this study, we showed that IFITM3 rs 12252-CC was over expressed in HCC patients compared to control group with HCV infection., Method: DNA sequencing was applied for detection of IFITM3 rs 12252-CC and IFITM3 protein level was measured by ELISA to 50 patients with HCC with cirrhosis and 50 with Hepatitis C virus infection., Results: The obtained results of this study indicated that IFITM3 rs 12252-CC was significantly elevated in HCC group, the codominant model of CC genotype of IFITM3 gene had high association with risk of hepatocellular carcinoma with odd ratio (OR) = 2.70, p = 0.041., Conclusion: IFITM3 play an important role in progression of hepatocellular carcinoma. Results revealed that IFITM3 rs 12252-CC among Hepatocellular carcinoma patients would allow diagnosis and starting intervention., (© 2023. The Author(s).)

Background: Hepatocellular carcinoma originates from hepatocytes as a result of the effects of numerous genetic variations. Interferon-Induced Transmembrane protein 3 (IFITM3) is involved in the processes of cellular differentiation, apoptosis, cell adhesion, and immune cell regulation. Matrix Metalloproteinase-9 (MMP-9) are zinc dependent endopeptidases that cleave extracellular matrix contents and play an important role in the progression of cancer., Objective: The study aimed to outline the key molecular biology progression in hepatocellular carcinoma and the relationship between hepatocellular cancer and genetic polymorphisms of IFITM3 and MMP-9., Methods: In total 200 patients with hepatocellular carcinoma patients (n=100) and a control group with Hepatitis C virus (n=100) which collected randomly from the EL-Mansoura oncology center during the interval between June 2020 and October 2021. The expression of MMP-9 and the IFITM3 SNP was investigated. MMP-9 gene polymorphisms were estimated by using PCR-RFLP and IFITM3 gene was detected using DNA sequencing, ELISA was used to measure protein levels of MMP-9 and IFITM3., Results: The T allele of MMP-9 was more frequent among patients (n=121) than control subjects (n=71). The C allele of IFITM3 was more frequent among patients (n=112) than control subjects (n=83), polymorphisms of the genes linked to a high risk of disease development, patients of MMP-9 (TT genotype), odd ratio (OR) = 2.63, IFITM3 (CC genotype), OR= 2.43., Conclusions: We found that the genetic polymorphisms of MMP-9 and IFITM3 are related to the occurrence and development of hepatocellular carcinoma. This study might be utilized in clinical diagnosis and therapy and to provide a baseline for prevention., Competing Interests: Declaration of Competing Interest The authors declare no competing interests. I and other authors declare that we have no proprietary, financial, professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the position presented in, or the review of, the manuscript entitled,, (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Background: Our study survey assessed HIV risk profile and pre-exposure prophylaxis (PrEP) use among HIV-negative individuals seeking mpox vaccination, elucidating HIV prevention gaps and opportunities., Methods: Anonymous cross-sectional surveys were self-administered at an urban academic center clinic in New Haven, CT, U.S. (August 18-November 18, 2022). Inclusion criteria included adults presenting for mpox vaccination who consented to the study. The study assessed STI risk (sexual practices, STI history, substance use). For HIV-negative participants, PrEP knowledge, attitudes, and preferences were assessed., Results: Eighty-one of 210 individuals approached completed surveys (survey acceptance and completion rate 38.6%). Majority were cisgender-male (76/81; 93.8%), Caucasian (48/79; 60.8%), with median age 28 years (IQR-15). Nine of 81 (11.5%) self-reported HIV-positivity. Median sexual partner number (6 months prior) was 4 (IQR-5.8). Majority, 89.9% and 75.9%, reported insertive and receptive anal intercourse, respectively. 41% reported lifetime STI history, of whom 12.3% had an STI 6 months prior. Majority (55.8%) used ≥ 1 illicit substance; 87.7% moderate alcohol use. Among HIV-negative respondents, most (95.7%) were aware of PrEP, but only 48.4% used PrEP., Conclusion: Individuals seeking mpox vaccination engage in behaviors placing them at increased STI risk and would benefit from PrEP assessment., (© 2023. The Author(s).)

Background: Approximately 215 million Americans have been fully vaccinated for COVID-19, representing over 65% of the total population. People with HIV (PWH) may be more susceptible to COVID-19 infection or severe disease, elevating the importance of COVID-19 vaccination uptake in the population. We report results from a national survey of PWH to evaluate the likelihood of receiving a COVID-19 vaccine., Methods: We conducted an online survey of 1,030 PWH living in the United States between December 6, 2020 and January 8, 2021 to evaluate likelihood of receiving a COVID-19 vaccine., Results: Overall, participants were highly willing to be vaccinated, with 83.8% stating they "strongly agree" (65.7%) or "somewhat agree" (18.1%). Participants' top vaccine-related concerns were side-effects (39.3%), safety (14.7%), and fair/equitable distribution of the vaccine to affected communities (13.6%). Participants were more willing to be vaccinated if they reported receiving an annual influenza vaccination ( p < 0.001), had previously tested positive for ( p = 0.043) COVID-19, had been hospitalized for ( p = 0.027) COVID-19 infection, or had an undetectable HIV viral load ( p = 0.002). Black ( p < 0.001), politically conservative ( p < 0.001), and participants with an annual income of ≤ $19,999 ( p = 0.005) were significantly less willing to be vaccinated for COVID-19., Conclusions: The vast majority of PWH were willing to be vaccinated, though predominantly those who were already engaged in HIV care or directly affected by COVID-19. Findings from this large survey of PWH suggest intensive outreach efforts are needed to support engagement in vaccination programs, particularly among Black and politically conservative PWH., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wickersham, Meyer, Shenoi, Altice, Barakat, Virata, Olivares, Maviglia, Khati and Shrestha.)

To characterize perspectives and experiences with telemedicine during the COVID-19 pandemic, we conducted a mixed-methods study in two HIV clinics in the US Northeast. Among surveyed patients with HIV (PWH) who had a telemedicine appointment (n = 205), 42.4% perceived telemedicine visits as useful during the pandemic. PWH and clinical staff identified benefits of telemedicine: (1) ability to engage and re-engage patients in care; (2) perceived patient-centeredness and flexibility; (3) opportunity to engage family and multidisciplinary care team members; and (4) opportunity to enhance telemedicine use proficiency through practice and support. Identified barriers included: (1) technical challenges; (2) privacy concerns; (3) loss of routine clinical experiences and interactions; (4) limited objective patient remote monitoring; and (5) reimbursement concerns. Efforts to optimize telemedicine for HIV care should consider strategies to improve technology support for PWH, flexible options to access care, additional platforms to allow patient remote monitoring, and appropriate billing and reimbursement methods., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Early accurate breast cancer (BC) diagnosis is critical in disease management. Mammography has been widely used. However, its radiation, and high false-negative and -positive results have always been a concern. We evaluated combined detection of human epididymal protein 4 (HE4) and trefoil factor 3 (TFF3) as substitute method to enhance BC diagnosis., Methods: HE4 and TFF3 blood levels were determined by ELISA in sera of 120 BC patients and 80 women (40 healthy and 40 benign breast disease) as controls. Receiver-operating characteristic curve was applied for evaluation diagnostic power of each biomarker and their combination., Results: In BC patients, serum HE4 [5 (2-11.9) vs. 3.1 (1.8-5.4) and 1 (1-3.5); P = 0.022] and TFF3 [5.3 (4.5-6.7) vs. 4.7 (4-4.8) and 3.9 (3-4.4); P = 0.027] were significantly higher than that in benign and healthy groups, respectively. Both HE4 (AUC = 0.783; P < 0.0001) and TFF3 (AUC = 0.759; P < 0.0001) had superior BC diagnostic ability compared to CEA and CA-15.3. Logistic regression analysis revealed simplified index BC-DETECT = HE4 + TFF3, and its values were significantly (P = 0.0132) elevated in BC (10.9 (8.4-17.2) compared to benign (7.2 (5.4-10.1)) and healthy (5.1 (4-6.3)) controls. AUC of BC-DETECT for BC prediction was (AUC = 0.850; P < 0.0001) with sensitivity, specificity, and positive and negative predictive values and accuracy of 84.2%, 70%, 80.8%, 74.7%, and 78.5%, respectively. High BC-DETECT levels were associated with tumor non-luminal subtypes, late stage, high grade, large size, lymph-node invasion, and multiple lesions., Conclusions: BC-DETECT is inexpensive, rapid, and easy to perform and reliably guides BC early detection. Moreover, the association between elevated BC-DETECT values and disease severity may propose its potential role as prognostic marker., (© 2022. The Author(s), under exclusive licence to The Japanese Breast Cancer Society.)

There continue to be conflicting data regarding the outcomes of people with HIV (PWH) who have COVID-19 infection with most studies describing the early epidemic. We present a single site experience spanning a later timeframe from the first report on January 21, 2020 to January 20, 2021 and describe clinical outcomes and predictors of hospitalization among a cohort of PWH in an urban center in Connecticut, USA. Among 103 PWH with controlled HIV disease, hospitalization occurred in 33% and overall mortality was 1%. HIV associated factors (CD4 count, HIV viral suppression) were not associated with hospitalization. Chronic lung disease (OR: 3.35, 95% CI:1.28-8.72), and cardiovascular disease (OR: 3.4, 95% CI:1.27-9.12) were independently associated with hospitalization. An increasing number of non-communicable comorbidities increased the likelihood of hospitalization (OR: 1.61, 95% CI:1.22-2.13)., Competing Interests: Sheela Shenoi’s spouse worked for Merck Pharmaceuticals from 1997 to 2007 and retains company stock in his retirement account. While no conflict of interest is involved, this information is included here in the interest of full disclosure. All other authors report no potential conflicts of interest. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: HIV/AIDS remains one of the world's most significant public health challenges; sub-Saharan Africa accounts for 71% of the global burden of HIV. Testing for HIV is pivotal to achieving UNAIDS 95-95-95 target towards bringing an end to the epidemic., Objective: The study assessed five-year HIV testing data from the largest tertiary hospital in Monrovia, Liberia and highlights risk groups that would benefit from targeted testing and prevention interventions., Methods: This was a single-center academic hospital-based retrospective analysis of HIV testing data from January 2014 to December 2018 obtained from all testing sites at John F. Kennedy Medical Center in Monrovia, Liberia. Pooled HIV testing data during the study period were analyzed using descriptive statistics and stratified by age, gender and pregnancy status. Annual diagnoses rates were reported as proportion of individuals tested within a specified category (age [<15 years, age 15-24 years and >=25 years], gender, and pregnancy status) that had a positive HIV test. Five-year trends were analyzed., Results: Over the study period, 41,343 non-pregnant individuals were screened for HIV. In addition, the antenatal clinic performed 24,913 tests. Of non-pregnant individuals tested, 4,066 (10%) were diagnosed with HIV ranging from 7% (909/12821) in 2018 to 13% (678/5079) in 2014. Case detection rates for individuals aged 15-24 were 7%, 5%, 4%, 6% and 3% for years 2014, 2015, 2016, 2017 and 2018 respectively. Annually, 2-3% of all pregnant women tested were diagnosed with HIV. While HIV detection rates decreased over time overall, children less than 15 years of age showed an annual increase from 6.7% in 2014 to 12.3% in 2018., Conclusion: A large five-year dataset from the largest tertiary facility in Liberia shows broad HIV detection rates that are much higher than national prevalence estimates. Ramping up HIV testing and prevention interventions including pre-exposure prophylaxis are sorely needed., Competing Interests: The authors have no competing interests to declare., (Copyright: © 2021 The Author(s).)

Background: Late diagnosis of human immunodeficiency virus (HIV) is associated with increased morbidity and mortality, and represents a serious public health concern., Methods: A retrospective medical record review was conducted on 188 patients with newly diagnosed HIV at a large academic center's HIV clinic from 1/2010 to 12/2019. Patient demographic data, HIV staging, and response to combination antiretroviral therapy (cART) as measured by HIV viral suppression at 12 weeks (HIV RNA < 50 copies) were collected. Bivariate analyses were applied to compare patients ≥50 years old to those < 50 years old., Results: Over two-thirds of the older patients with a new diagnosis of HIV presented with a CD4 count < 200, or an AIDS-defining illness. Though not statistically significant, this same group also had a delay to viral suppression with only 59% achieving viral suppression after 12-weeks of cART initiation., Conclusions: This study suggests that older patients are presenting to care with advanced stages of HIV, and may also have a delay in achieving viral suppression after cART initiation. Future studies should aim to target HIV testing and treatment strategies for this at-risk older adult group.

Background: COVID-19 is caused by the severe acute respiratory syndrome virus SARS-CoV-2. It is widely recognized as a respiratory pathogen, but neurologic complications can be the presenting manifestation in a subset of infected patients., Case Presentation: We describe a 78-year old immunocompromised woman who presented with altered mental status after witnessed seizure-like activity at home. She was found to have SARS-CoV-2 infection and associated neuroinflammation. In this case, we undertake the first detailed analysis of cerebrospinal fluid (CSF) cytokines during COVID-19 infection and find a unique pattern of inflammation in CSF, but no evidence of viral neuroinvasion., Conclusion: Our findings suggest that neurologic symptoms such as encephalopathy and seizures may be the initial presentation of COVID-19. Central nervous system inflammation may associate with neurologic manifestations of disease.

Background: There is an anticipated shortage of primary care providers trained to care for patients with HIV. The Yale School of Medicine developed and implemented a novel HIV training track within our Primary Care Internal Medicine Residency Program. A set of 12 Entrustable Professional Activities (EPAs) were developed to guide curriculum development and resident assessment., Aim: To describe the process of implementing a novel EPA-based curriculum for the HIV Primary Care Training Track including EPA-based trainee evaluation tools., Participants/settings: Two to three residents were enrolled annually from 2012 to 2017 (total n = 11). Training sites included the outpatient academic center HIV clinic and inpatient HIV ward., Program Description: An expert panel developed 12 HIV-specific EPAs. These were mapped to curricular and reporting internal medicine milestones. Curricular activities and evaluation tools were developed to guide EPA progress., Program Evaluation: Graduating residents were ready for unsupervised practice in 91% of EPAs at the end of the 3-year program., Discussion: Development of HIV-specific training EPAs was effective for driving curricular development and resident evaluation, and served as an effective method to communicate expectations to resident participants. These HIV-specific EPAs could serve as a useful template to enhance HIV education in academic settings.

For persons living with HIV and AIDS (PLWHA), care by an HIV-specialist improves outcomes and satisfaction with one's HIV primary care provider (PCP) promotes engagement with care. In the United States, we are facing a workforce shortage of HIV providers. As we aim to train a new generation of HIV providers, it is unclear how PLWHA perceive their experience when cared for by trainees compared to experienced providers. Therefore we assessed patient satisfaction with HIV providers, both trainees in an HIV Primary Care residency program and HIV-specialists. A secondary objective was to evaluate providers' performance in adhering to standard management guidelines for HIV-associated and non-HIV-associated conditions. We surveyed 75 PLWHA, including 51 (68%) assigned to an HIV-specialist PCP and 24 (32%) to a trainee PCP. Overall patient satisfaction on a 10-point scale was similar (mean 9.6 HIV-specialist vs 9.7 trainee, p = 0.71) and remained similar in multivariate logistic regression analysis when controlling for patient age, gender, race, and recently establishing care (Odds Ratio 1.1, 95% Confidence Interval 0.3-5.0). Participants in the trainee group were more likely to feel their provider "always" spent enough time with them (100% vs 81%, p = 0.03). Adherence to HIV guidelines was similar, though trainees were more likely to document counseling on risk reduction (83% vs 47%, p = 0.005) and adherence to antiretroviral therapy (100% vs 66%, p = 0.001). In conclusion, in a structured HIV-training program, residents can provide subspecialty level care in an HIV continuity clinic with levels of performance and patient satisfaction equivalent to those of experienced specialists.

Problem: People with HIV/AIDS are living longer and are at an increased risk of comorbidities. A qualified physician workforce is needed to care for this growing population., Approach: In 2012, a novel three-year HIV training track (HIV TT) was implemented as part of the Yale Primary Care Residency Program. To prepare for the implementation of this program, a needs assessment was performed, a web-based curriculum and 12 HIV-specific entrustable professional activities (EPAs) were created, and adequate clinical training opportunities in HIV and primary care were established. Program evaluation included process, learner, and outcome evaluations from 2012 to 2017., Outcomes: Since its inception, the HIV TT has enrolled a total of 11 residents (6-7 at a time), with 5 graduating to date. Residents delivered high-quality HIV and primary care for a diverse panel of patients; improved their knowledge and performance in HIV care, including according to the HIV-specific EPAs; and were highly satisfied with the program. All faculty remained with the program, and patients indicated satisfaction., Next Steps: Next steps include enhanced coordination of residents' schedules, improved EPA documentation, evaluation of residents' HIV and non-HIV competence beyond residency, and monitoring graduates' career trajectories. Expanding HIV training within internal medicine residency programs is feasible and effective and has the potential to alleviate the shortage of physicians trained to provide HIV care and primary care in a single setting.

Objective: Very-low-level viremia (VLLV) is a relatively new concept in the realm of human immunodeficiency virus (HIV) care. Newer generation assays are now able to detect plasma HIV RNA Viral Load (VL) levels as low as 20 copies/mL. The authors characterized patients with VLLV (VL between 20 and 50 copies/mL) in order to identify possible risk factors associated with virologic failure and poor clinical outcomes., Methods: The authors reviewed 119 consecutive charts of patients with VLLV. Sociodemographic data were extracted and viral load and CD4 counts were trended over a 12 month period (February 2013-February 2014). Regression analysis was used to assess the role of different factors on virologic failure at 1 year., Results: Of the study participants with evaluable data (n = 100), the median age was 53 years (interquartile range: 43-57.5), 67% were nonwhite, 34% were women, 58% were smokers, 47% were alcoholics, 58% had a history of intravenous drug use, and 40% were coinfected with hepatitis C virus. More than half of the participants had 3 or more comorbidities and their HIV pill burden was high (more than 2 pills daily). After 12 months, 65 participants achieved undetectable viral load levels, whereas 15 experienced virologic failure (2 consecutive viral loads > 50 copies/mL) and the remaining 20 had persistent VLLV. In the virologic failure group, there was a predominance of white males (66%) with a significant number of comorbidities and pill burden. Univariate logistic regression suggested that there was a difference between the failure versus nonfailure groups in terms of race, ethnicity, and alcohol use. Multivariate regression with virological failure as the outcome suggested a trend only in terms of participant's alcohol use., Conclusion: Most patients with initial VLLV (70%) achieved virologic suppression at 1 year with no antiretroviral therapy changes. Thus, VLLV does not necessarily predict virologic failure and should not prompt more frequent clinic visits or antiretroviral regimen changes. Further research is needed in order to determine the predictors of virologic failure in this subset of patients and the clinicians' attitude toward VLLV.

Currently, the search for suitable hepatocellular carcinoma (HCC) biomarkers is very intensive. Besides, efficacy and cost/effectiveness of screening and surveillance of cirrhotics for the diagnosis of HCC is still debated. So, the present study is concerned with the evaluation of cytokeratin-1 (CK-1) and nuclear matrix protein-52 (NMP-52) for identifying HCC. Two-hundred and eighty individuals categorized into three groups [liver fibrosis (F1-F3), cirrhosis (F4), and HCC] constituted this study. Western blot was used for identifying CK-1 and NMP-52 in serum samples. As a result, a single immunoreactive band was shown at 67 and 52 kDa corresponding to CK-1 and NMP-52, respectively. Both CK-1 and NMP-52 bands were cut and electroeluted separately. These markers were quantified in sera using ELISA. Patients with HCC were associated with higher concentrations of CK-1 and NMP-52 than those without HCC with a significant difference (P < 0.0001). CK-1 showed an area under receiver-operating characteristic curve (AUC) of 0.83 with 75 % sensitivity and 82 % specificity while NMP-52 yielded 0.72 AUC with 62 % sensitivity and 70 % specificity for identifying HCC. HCC-DETECT comprising CK-1 and NMP-52 together with AFP was then constructed yielding 0.90 AUC for identifying HCC with 80 % sensitivity and 92 % specificity. HCC-DETECT was then tested for separating HCC from F1-F3 showing 0.94 AUC with 80 % sensitivity and 93 % specificity. In conclusion, CK-1 in conjunction with NMP-52 and AFP could have a potential role for improving the detection of HCC with a high degree of accuracy.

Objective: Mortality in hospitalized human immunodeficiency virus (HIV)-infected patients is not well described. We sought to characterize in-hospital deaths among HIV-infected patients in the antiretroviral (ART) era and identify factors associated with mortality., Methods: We reviewed the medical records of hospitalized HIV-infected patients who died from January 1, 1995 to December 31, 2011 at an urban teaching hospital. We evaluated trends in early and late ART use and deaths due to acquired immunodeficiency syndrome (AIDS) and non-AIDS, and identified clinical and demographic correlates of non-AIDS deaths., Results: In-hospital deaths declined significantly from 1995 to 2011 (P < 0.0001); those attributable to non-AIDS increased (43% to 70.5%, P < 0.0001). Non-AIDS deaths were most commonly caused by non-AIDS infection (20.3%), cardiovascular (11.3%) and liver disease (8.5%), and non-AIDS malignancy (7.8%). Patients with non-AIDS compared to AIDS-related deaths were older (median age 48 vs 40 years, P < 0.0001), more likely to be on ART (74.1% vs 55.8%, P = 0.0001), less likely to have a CD4 count of <200 cells/mm(3) (47.2% vs 97.1%, P < 0.0001), and more likely to have an HIV viral load of ≤400 copies/mL (38.1% vs 4.1%, P < 0.0001). Non-AIDS deaths were associated with 4.5 and 4.2 times greater likelihood of comorbid underlying liver and cardiovascular disease, respectively., Conclusions: Non-AIDS deaths increased significantly during the ART era and are now the most common cause of in-hospital deaths; non-AIDS infection, cardiovascular and liver disease, and malignancies were major contributors to mortality. Higher CD4 cell count, liver, and cardiovascular comorbidities were most strongly associated with non-AIDS deaths. Interventions targeting non-AIDS-associated conditions are needed to reduce inpatient mortality among HIV-infected patients., (© 2015 Society of Hospital Medicine.)

Background: Atherosclerosis remains one of the leading causes of death all over the world. Flax, pumpkin and purslane seeds are rich sources of unsaturated fatty acids, antioxidants and fibers, known to have antiatherogenic activities., Aims: This study was to examine the efficiency of using either flax/pumpkin or purslane/pumpkin seed mixture (components of ω-3 and ω-6) on hyperlipidemia, kidney function and as immunomodulators in rats fed high cholesterol diets., Materials and Methods: 40 male albino rats were divided into four groups: control group, hypercholesterolemic rats, fed the balanced diet supplemented with cholesterol at a dose level of 2 g/100 g diet; the other two groups of animals fed the same previous hypercholesterolemic diet supplemented with either flax/pumpkin seed mixture or pumpkin/purslane seed mixture at ratio of (5/1) (ω-3 and ω-6)., Results: The present study showed that 2% cholesterol administration caused a significant increase in total cholesterol, total lipids, and triacylglycerol in both serum and liver. Serum phospholipids, LDL-C, and atherogenic index AI also significantly increased compared to control group. Cholesterol-enriched diet significantly increased serum urea, creatinine, sodium and potassium levels as well as significantly increased serum IgG and IgM compared to healthy control. Consumption of flax/pumpkin or purslane/pumpkin seed mixtures by hypercholesterolemic rats resulted in a significantly decrement in lipid parameters and significant improvement in IgG and IgM levels as compared with hypercholesterolemic rats., Conclusion: Our results suggests that both flax/pumpkin and purslane/pumpkin seed mixtures had anti-atherogenic hypolipidemic and immunmodulator effects which were probably mediated by unsaturated fatty acids (including alpha linolenic acid) present in seed mixture.

Context: Complicated left-sided native valve endocarditis causes significant morbidity and mortality in adults. Lack of valid data regarding estimation of prognosis makes management of this condition difficult., Objective: To derive and externally validate a prognostic classification system for adults with complicated left-sided native valve endocarditis., Design, Setting, and Patients: Retrospective observational cohort study conducted from January 1990 to January 2000 at 7 Connecticut hospitals among 513 patients older than 16 years who experienced complicated left-sided native valve endocarditis and who were divided into derivation (n = 259) and validation (n = 254) cohorts., Main Outcome Measure: All-cause mortality at 6 months after baseline., Results: In the derivation and validation cohorts, the 6-month mortality rates were 25% and 26%, respectively. Five baseline features were independently associated with 6-month mortality (comorbidity [P =.03], abnormal mental status [P =.02], moderate to severe congestive heart failure [P =.01], bacterial etiology other than viridans streptococci [P<.001 except Staphylococcus aureus, P =.004], and medical therapy without valve surgery [P =.002]) and were used to create a prognostic classification system. In the derivation cohort, patients were classified into 4 groups with increasing risk for 6-month mortality: 5%, 15%, 31%, and 59% (P<.001). In the validation cohort, a similar risk among the 4 groups was observed: 7%, 19%, 32%, and 69% (P<.001)., Conclusions: Adults with complicated left-sided native valve endocarditis can be accurately risk stratified using baseline features into 4 groups of prognostic severity. This prognostic classification system might be useful for facilitating management decisions.

We describe the 11th case of bioterrorism-related inhalational anthrax reported in the United States. The presenting clinical features of this 94-year-old woman were subtle and nondistinctive. The diagnosis was recognized because blood cultures were obtained prior to administration of antibiotics, emphasizing the importance of this diagnostic test in evaluating ill patients who have been exposed to Bacillus anthracis. The patient's clinical course was characterized by progression of respiratory insufficiency, pleural effusions and pulmonary edema, and, ultimately, death. Although her B anthracis bacteremia was rapidly sterilized after initiation of antibiotic therapy, viable B anthracis was present in postmortem mediastinal lymph node specimens. The source of exposure to B anthracis in this patient is not known. Exposure to mail that was cross-contaminated as it passed through postal facilities contaminated with B anthracis spores is one hypothesis under investigation.