Going to the Source: Discussions With Early and Mid-Career Faculty From Groups Underrepresented in Biomedical Research to Develop and Enhance CFAR Services.

BACKGROUND: To include, sustain, and retain HIV-focused early career faculty from groups historically excluded from biomedical research, the Providence/Boston Center for AIDS Research (CFAR) conducted focus groups and individual interviews with early and mid-career faculty to discern their needs. METHODS: We conducted focus groups and interviews with 15 faculty at institutions affiliated with Providence/Boston CFAR from groups underrepresented in biomedical research. The discussion was guided using the domains of an Asset Bundle Model encompassing scientific human capital, social capital, and financial capital. RESULT: Participants' identities, including their race, ethnicity, gender, sexual orientation, and being a parent affected their vision of themselves as scientists. Participants reported confusion or limited training on or access to resources for professional development, hiring staff, meeting NIH reporting requirements, international research, support for working parents, sabbaticals, and addressing workplace conflict or unsupportive work environments. Some described feeling like they were a burden on their mentors who seemed overextended. They identified attributes of effective mentors, such as believing in and investing in the mentee; having the requisite content area expertise and self-confidence; being able to identify mentees needs and meet them where they are; and being consistent, communicative, respectful, and kind. They described a need for additional education and support preresearch and postresearch grant award management. CONCLUSIONS: To learn how to equitably serve all interested in HIV research, CFARs should engage and include perspectives from scientists who have historically been excluded from biomedical research. Our future work will test, implement, and disseminate the ideas generated by these focus group discussions.

Evaluating Barriers to Viral Suppression among People with HIV in Santiago, Dominican Republic.

The Dominican Republic (DR) has the second-highest prevalence of HIV infection in the Caribbean, but viral suppression and treatment adherence are not well understood. We conducted a cross-sectional study among people living with HIV/AIDS(PLWHA) to fill in the knowledge gap. Questionnaire was used to collect demographic data, antiretroviral therapy (ART) adherence, and barriers and facilitators to HIV care. Viral load and other clinical information were extracted through chart reviews. Descriptive analyzes and logistic regression were conducted to explore factors associated with non-viral suppression and imperfect ART adherence. Of 193 PLWHA 83.9% were virally suppressed. Those that were non-virally suppressed were more likely of being male (odds ratio [OR]: 2.55, 95% confidence interval [CI]: 1.17-5.58) and less likely of being unemployed (OR: 0.28, 95% CI: 0.08-0.96). However, being male (OR: 0.78, 95% CI:0.40-1.53) and unemployed (OR: 0.28, 95% CI:0. 08-1.21) were less likely to report imperfect adherence. Tailored interventions are needed to improve adherence and viral suppression in DR.

Healthcare Providers' Views on Hepatitis C Testing and Counseling Among Sexual Partners of Hepatitis-C-Infected Persons: An Online Survey.

BACKGROUND: Current hepatitis C virus (HCV) counseling guidelines do not recommend that HCV-infected patients notify their partners or encourage them to get tested. We aimed to assess healthcare professionals' knowledge of and attitudes toward counseling and testing recommendations for HCV-infected patients. METHODS: A 15-question, anonymous survey was designed and distributed via email to a convenience sample of healthcare professionals who work with Brown University or Boston University affiliated hospitals to assess their knowledge of and attitudes toward counseling recommendations for HCV-infected patients. The data was collected electronically and analyzed using descriptive statistical methods. RESULTS: Of the 55 respondents (a 20% response rate), 73% incorrectly believed that, at the time the survey was completed, CDC HCV testing guidelines already recommended partners of HCV-infected patients be tested for HCV infection. Furthermore, 80% of respondents believed recommendations should be revisited to explicitly include that HCV-infected patients encourage their partners to get tested. When counseling patients with HCV, 44% of respondents reported they always ask whether the patient's partners have been tested for HCV and 42% reported they sometimes do. Similarly, 42% reported they always suggest that the HCV-infected patient's partners be tested for HCV. CONCLUSIONS: Our survey shows that healthcare providers believe that HCV-counseling and testing recommendations could be revisited, with specific attention given to the promotion of HCV testing for partners of HCV-infected patients.

Remdesivir Use Compared With Supportive Care in Hospitalized Patients With Severe COVID-19: A Single-Center Experience.

BACKGROUND: The US Food and Drug Administration issued an Emergency Use Authorization for remdesivir use in patients with severe COVID-19. METHODS: We utilized data from 2 quaternary acute care hospitals. The outcomes of interest were the impact of remdesivir on in-hospital death by day 28 and time to recovery, clinical improvement, and discharge. We utilized Cox proportional hazards models and stratified log-rank tests. RESULTS: Two hundred twenty-four patients were included in the study. The median age was 59 years; 67.0% were male; 17/125 patients (13.6%) who received supportive care and 7/99 patients (7.1%) who received remdesivir died. The unadjusted risk for 28-day in-hospital death was lower for patients who received remdesivir compared with patients who received supportive care (hazard ratio [HR], 0.42; 95% CI, 0.16-1.08). Although this trend remained the same after adjusting for age, sex, race, and oxygen requirements on admission (adjusted HR [aHR], 0.49; 95% CI, 0.19-1.28), as well as chronic comorbidities and use of corticosteroids (aHR, 0.44; 95% CI, 0.16-1.23), it did not reach statistical significance. The use of remdesivir was not associated with an increased risk of acute kidney injury (AKI) or liver test abnormalities. Although not statistically significant, the rate ratios for time to recovery, clinical improvement, and discharge were higher in women and black or African American patients. CONCLUSIONS: Patients on remdesivir had lower, albeit not significant, all-cause in-hospital mortality, and the use of remdesivir did not increase the risk for AKI. Promising signals from this study need to be confirmed by future placebo-controlled randomized clinical trials.

Short-Term Dexamethasone in Sars-CoV-2 Patients.

BACKGROUND: Dexamethasone, a synthetic glucocorticoid, has anti-inflammatory and immunosuppressive properties. There is a hyperinflammatory response involved in the clinical course of patients with pneumonia due to SARS-CoV-2. To date, there has been no definite therapy for COVID-19. We reviewed the charts of SARS-CoV-2 patients with pneumonia and moderate to severely elevated CRP and worsening hypoxemia who were treated with early, short-term dexamethasone. METHODS: We describe a series of 21 patients who tested positive for SARS-CoV-2 and were admitted to The Miriam Hospital in Providence, RI, and were treated with a short course of dexamethasone, either alone or in addition to current investigative therapies. RESULTS: CRP levels decreased significantly following the start of dexamethasone from mean initial levels of 129.52 to 40.73 mg/L at time of discharge. 71% percent of the patients were discharged home with a mean length of stay of 7.8 days. None of the patients had escalation of care, leading to mechanical ventilation. Two patients were transferred to inpatient hospice facilities on account of persistent hypoxemia, in line with their documented goals of care. CONCLUSIONS: A short course of systemic corticosteroids among inpatients with SARS-CoV-2 with hypoxic respiratory failure was well tolerated, and most patients had improved outcomes. This limited case series may not offer concrete evidence towards the benefit of corticosteroids in COVID-19. However, patients' positive response to short-term corticosteroids demonstrates that they may help blunt the severity of inflammation and prevent a severe hyperinflammatory phase, in turn reducing the length of stay, ICU admissions, and healthcare costs.

COVID-19 in a Patient Presenting with Syncope and a Normal Chest X-ray.

SARS-CoV-2 is a novel virus that has now affected hundreds of thousands of individuals across the world. Amidst this global pandemic, maintaining a high index of suspicion, rapid testing capacity, and infection control measures are required to curtail the virus' rapid spread. While fever and respiratory symptoms have been commonly used to identify COVID-19 suspects, we present an elderly female who arrived to the hospital after a syncopal episode. She was afebrile with a normal chest X-ray and there was no suspicion of COVID-19. She then developed a fever and tested positive for COVID-19. Our unique case underscores the increasing diversity of COVID-19 presentations and potential for initial mis- diagnosis and delay in implementing proper precautions.

Falling Through the Cracks: Risk Factors for Becoming Lost to HIV Care After Incarceration in a Southern Jail.

Using a retrospective cohort analysis of inmates released from Dallas County Jail between January 2011 and November 2013, this study characterizes people living with HIV/AIDS (PLWHA) who are lost to care after release from jail. We used Kaplan-Meier analysis to estimate the risk of becoming lost to post-release HIV care and a Cox proportional hazards regression model to identify associated factors. The majority of individuals (78.2%) were men and 65.5% were black. Of the incarcerations that ended with release to the community, approximately 43% failed to link to community HIV care. Non-Hispanic Whites were more likely than Hispanics or Blacks to drop out of care after release. Individuals with histories of substance use or severe mental illness were more likely to become lost, while those under HIV care prior to incarceration and/or who had adhered to antiretroviral therapy (ART) were more likely to resume care upon release. Targeted efforts such as rapid linkage to care and re-entry residence programs could encourage formerly incarcerated individuals to re-engage in care.

Increasing Syphilis in Rhode Island: Return of an Old Foe.

The number of people diagnosed with syphilis has increased significantly in the United States over the last decade. In Rhode Island, the number of new diagnoses has increased more than four-fold since 2008. Syphilis disproportionately impacts gay, bisexual, and other men who have sex with men (MSM), with those from African American and Hispanic/Latino communities most affected. Given these trends, physicians need to be aware of current prevention, diagnosis, and treatment practices for syphilis, especially when working with populations who are most at risk. [Full article available at http://rimed.org/rimedicaljournal-2019-02.asp].

A Nearly 50% Decrease in New HIV Diagnoses in Rhode Island from 2006-2016: Implications for Policy Development and Prevention.

In the last decade, reductions in HIV incidence have been observed across the United States. However, HIV continues to disproportionately impact gay, bisexual, and other men who have sex with men (MSM). In Rhode Island, rates of HIV diagnoses have decreased by 44% across all groups over the last decade. This success has been the result of close collaboration across multiple sectors. Different prevention approaches, including syringe exchange programs, community-based HIV testing, condom distribution, HIV care and treatment, and pre-exposure prophylaxis (PrEP) have all contributed to the decline in HIV diagnoses across the state. In 2015, Rhode Island became one of the first states to sign on to the Joint United Nations Programme on HIV/AIDS "90-90-90" campaign to end the HIV epidemic by 2030. Intensified and innovative initiatives are needed to improve progress in HIV prevention and treatment, especially in populations who are most at risk.

First confirmed case of Powassan neuroinvasive disease in Rhode Island.

The Powassan Virus is the arthropod-borne vector responsible for Powassan neuroinvasive disease. The virus was first isolated in 1958 and has been responsible for approximately 100 cases of neuroinvasive disease. Rates of infection have been on the rise over the past decade with numerous states reporting their first confirmed case; New Jersey, New Hampshire and Connecticut all reported their first case within the last five years. We present here the first confirmed case of Powassan neuroinvasive disease in the nearby state of Rhode Island. A previously healthy 81-year-old female with known tick exposure presented with fever, altered sensorium, seizures and focal neurological deficits. After an extensive work-up that was largely unrevealing Powassan encephalitis was suspected. The diagnosis was confirmed with serological testing consisting of Powassan IgM enzyme-linked immunosorbent assay and Powassan plaque reduction neutralization testing. The case study provides evidence for the increasing spread of Powassan neuroinvasive disease and reinforces the importance of requesting focused testing for Powassan Virus in patients from an endemic area with a clinically compatible syndrome.

Clinical Benefits and Cost-Effectiveness of Laboratory Monitoring Strategies to Guide Antiretroviral Treatment Switching in India.

Current Indian guidelines recommend twice-annual CD4 testing to monitor first-line antiretroviral therapy (ART), with a plasma HIV RNA test to confirm failure if CD4 declines, which would prompt a switch to second-line ART. We used a mathematical model to assess the clinical benefits and cost-effectiveness of alternative laboratory monitoring strategies in India. We simulated a cohort of HIV-infected patients initiating first-line ART and compared 11 strategies with combinations of CD4 and HIV RNA testing at varying frequencies. We included adaptive strategies that reduce the frequency of tests after 1 year from 6 to 12 months for virologically suppressed patients. We projected life expectancy, time on failed first-line ART, cumulative 10-year HIV transmissions, lifetime cost (2014 US dollars), and incremental cost-effectiveness ratios (ICERs). We defined strategies as cost-effective if their ICER was <1 × the Indian per capita gross domestic product (GDP, $1,600). We found that the current Indian guidelines resulted in a per person life expectancy (from mean age 37) of 150.2 months and a per person cost of $2,680. Adding annual HIV RNA testing increased survival by ∼8 months; adaptive strategies were less expensive than similar nonadaptive strategies with similar life expectancy. The most effective strategy with an ICER <1 × GDP was the adaptive HIV RNA strategy (ICER $840/year). Cumulative 10-year transmissions decreased from 27.2/1,000 person-years with standard-of-care to 20.9/1,000 person-years with adaptive HIV RNA testing. In India, routine HIV RNA monitoring of patients on first-line ART would increase life expectancy, decrease transmissions, be cost-effective, and should be implemented.

Assessing acceptability and feasibility of provider-initiated HIV testing and counseling in Ghana.

t In Ghana, HIV voluntary counseling and testing remains poorly utilized. The World Health Organization (WHO) has recommended opt-out, provider-initiated testing and counseling (PITC) in order to increase utilization and earlier intervention. Yet implementation challenges remain in resource-scarce settings. This study sought to better understand the dynamics of providing PITC at Apam Catholic Hospital, a district referral hospital in Ghana. Semi-structured interviews were conducted with healthcare providers and patients exploring attitudes regarding PITC, community stigma, and HIV knowledge. Results showed healthcare providers believed PITC would lead to earlier diagnosis and intervention, but concerns persisted over increased costs. Patients welcomed PITC, but expressed discomfort in opting-out. Patients demonstrated incomplete HIV knowledge and widely believed spiritual healers and prayer can cure the infection. Acceptance of PITC by both healthcare providers and patients remains high, but concerns over resource costs and HIV knowledge persist as challenges. [Full article available at http://rimed.org/rimedicaljournal-2017-08.asp].

Risk factors for poor multidrug-resistant tuberculosis treatment outcomes in Kyiv Oblast, Ukraine.

BACKGROUND: Ukraine is among ten countries with the highest burden of multidrug- resistant TB (MDR-TB) worldwide. Treatment success rates for MDR-TB in Ukraine remain below global success rates as reported by the World Health Organization. Few studies have evaluated predictors of poor MDR-TB outcomes in Ukraine. METHODS: We conducted a retrospective analysis of patients initiated on MDR-TB treatment in the Kyiv Oblast of Ukraine between January 01, 2012 and March 31st, 2015. We defined good treatment outcomes as cure or completion and categorized poor outcomes among those who died, failed treatment or defaulted. We used logistic regression analyses to identify baseline patient characteristics associated with poor MDR-TB treatment outcomes. RESULTS: Among 360 patients, 65 (18.1%) achieved treatment cure or completion while 131 (36.4%) died, 115 (31.9%) defaulted, and 37 (10.3%) failed treatment. In the multivariate analysis, the strongest baseline predictors of poor outcomes were HIV infection without anti-retroviral therapy (ART) initiation (aOR 10.07; 95% CI 1.20-84.45; p 0.03) and presence of extensively-drug resistant TB (aOR 9.19; 95% CI 1.17-72.06; p 0.03). HIV-positive patients initiated on ART were not at increased risk of poor outcomes (aOR 1.43; 95% CI 0.58-3.54; p 0.44). There was no statistically significant difference in risk of poor outcomes among patients who received baseline molecular testing with Gene Xpert compared to those who were not tested (aOR 1.31; 95% CI 0.63-2.73). CONCLUSIONS: Rigorous compliance with national guidelines recommending prompt initiation of ART among HIV/TB co-infected patients and use of drug susceptibility testing results to construct treatment regimens can have a major impact on improving MDR-TB treatment outcomes in Ukraine.

Patient predictors of poor drug sensitive tuberculosis treatment outcomes in Kyiv Oblast, Ukraine.

Background: Ukraine has high rates of poor treatment outcomes among drug sensitive tuberculosis (DSTB) patients, while global treatment success rates for DSTB remain high.     We evaluated baseline patient factors as predictors of poor DSTB treatment outcomes. Methods: We conducted a retrospective analysis of new drug sensitive pulmonary TB patients treated in Kyiv Oblast, Ukraine between November 2012 and October 2014. We defined good treatment outcomes as cure or completion and poor outcomes as death, default or treatment failure. We performed logistic regression analyses, using routine program data, to identify baseline patient factors associated with poor outcomes. Results: Among 302 patients, 193 (63.9%) experienced good treatment outcomes while 39 (12.9%) failed treatment, 34 (11.3%) died, and 30 (9.9%) defaulted. In the multivariate analysis, HIV positive patients on anti-retroviral therapy (ART) [OR 3.50; 95% CI 1.46 - 8.42; p 0.005] or without ART (OR 4.12; 95% CI 1.36 - 12.43; p 0.01) were at increased risk of poor outcomes. Alcohol abuse (OR 1.81; 95% CI 0.93 - 3.55; p 0.08) and smear positivity (OR 1.75; 95% CI 1.03 - 2.97; p 0.04) were also associated with poor treatment outcomes. Conclusions: High rates of poor outcomes among patients with newly diagnosed drug sensitive TB in Kyiv Oblast, Ukraine highlight the urgent need for programmatic interventions, especially aimed at patients with the highest risk of poor outcomes.

Engaging African and Caribbean Immigrants in HIV Testing and Care in a Large US City: Lessons Learned from the African Diaspora Health Initiative.

The lifting in 2010 of the HIV entry ban eliminated an access point for HIV testing of the foreign-born. The African Diaspora Health Initiative (ADHI) was developed to examine alternative pathways to testing for African and Caribbean persons. The ADHI consists of Clinics Without Walls (CWW) held in community settings. HIV testing is offered to participants along with hypertension and diabetes screening. A survey is administered to participants. Descriptive data were analyzed using SAS 9.2. Between 2011 and 2015, 4152 African and Caribbean individuals participated in 352 CWW. Participants were mostly (67.7 %) African. HIV rates were lowest in Caribbean women (0.4 %) and highest in Caribbean men (8.4 %). Efforts to engage African and Caribbean communities in HIV testing are important given the elimination of the HIV entry ban and continued immigration to the US from areas of higher prevalence. The ADHI offers a successful model of engagement.

Predictors of late virologic failure after initial successful suppression of HIV replication on efavirenz-based antiretroviral therapy.

BACKGROUND: Practical issues, including cost, hinder implementing virologic monitoring of patients on antiretroviral therapy (ART) in resource-limited settings. We evaluated factors that might guide monitoring frequency and efforts to prevent treatment failure after initial virologic suppression. METHODS: Participants were the 911 HIV-infected antiretroviral-naïve adults with CD4 count <300 cells/µL who started efavirenz-based ART in the international A5175/PEARLS trial and achieved HIV-1 RNA <1000 copies/mL at 24 weeks. Participant report of ART adherence was evaluated using a structured questionnaire in monthly interviews. Adherence and readily available clinical and laboratory measures were evaluated as predictors of late virologic failure (late VF: confirmed HIV-1 RNA ≥1000 copies/mL after 24 weeks). RESULTS: During median follow-up of 3.5 years, 82/911 participants (9%) experienced late VF. Of 516 participants reporting missed doses during the first 24 weeks of ART, 55 (11%) experienced late VF, compared with 27 (7%) of 395 participants reporting no missed doses (hazard ratio: 1.73; 95% CI: 1.08, 2.73). This difference persisted in multivariable analysis, in which lower pre-ART hemoglobin and absence of Grade ≥3 laboratory results prior to week 24 were also associated with higher risk of late VF. DISCUSSION: In this clinical trial, the late VF rate after successful suppression was very low. If achievable in routine clinical practice, virologic monitoring involving infrequent (e.g. annual) measurements might be considered; the implications of this for development of resistance need evaluating. Patients reporting missed doses early after ART initiation, despite achieving initial suppression, might require more frequent measurement and/or strategies for promoting adherence.

Attitudes Toward HIV Pre-Exposure Prophylaxis in a United States Urban Clinic Population.

A majority of US studies on attitudes toward PrEP focus on men who have sex with men with little representation of African Americans. This cross-sectional study seeks to determine openness to PrEP, and examine motivations for openness among Philadelphia residents. Patients undergoing HIV rapid testing between May 2012 and December 2014 in a public setting were administered a survey. Questions included openness to PrEP and reasons for openness to PrEP. Multivariate logistic regression models were used to investigate associations between openness and potential predictors. Analyses were conducted using R version 3.2.4 and the epitools and car packages. Of 5606 respondents, over 90 % were African American. Men were more likely to express openness (61.4 % of men, 54.8 % of women, p < 0.0001). Predictors of openness were younger age, black race, higher perceived risk for HIV by patient or as assessed by Tester, intermittent /no condom use, greater number of partners in 12 months and previous HIV testing. The main reason for openness was fear of HIV, and for disinterest was lack of recognition of risk. Understanding openness to PrEP, and reasons for openness to or disinterest in PrEP are critical to determining the best approaches to facilitate engagement in PrEP care by communities and persons at elevated risk for HIV acquisition. Further study is needed on how best to manage disinterest in PrEP by those at high risk for HIV, and how openness to PrEP translates into concrete steps to take PrEP.

Characterizing the Burden of Hepatitis C Infection Among Entrants to Pennsylvania State Prisons, 2004 to 2012.

Although hepatitis C (HCV) infection is common among prisoners, relatively few undergo evaluation for treatment. This study reports the prevalence of chronic infection and the genotype distribution among an incarcerated population. HCV antibody testing was provided to adults entering Pennsylvania prisons; confirmatory and genotype testing were offered to those eligible for treatment. Antibody prevalence among 101,727 individuals was 18.1%. Among 7,633 individuals who underwent confirmatory testing, 69.3% had detectable RNA. Among 3,247 individuals who underwent genotype testing, genotype 1 was the most common (76.6%). The rate of chronic infection after HCV exposure is similar to that reported in the community, as is genotype distribution. Correctional facilities provide access to a population with a high disease burden, creating a public health opportunity for evaluation and treatment.

Epidemiology of hepatitis C virus in Pennsylvania state prisons, 2004-2012: limitations of 1945-1965 birth cohort screening in correctional settings.

OBJECTIVES: We described hepatitis C virus antibody (anti-HCV) prevalence in a state prison system and retrospectively evaluated the case-finding performance of targeted testing of the 1945 to 1965 birth cohort in this population. METHODS: We used observational data from universal testing of Pennsylvania state prison entrants (June 2004-December 2012) to determine anti-HCV prevalence by birth cohort. We compared anti-HCV prevalence and the burden of anti-HCV in the 1945 to 1965 birth cohort with that in all other birth years. RESULTS: Anti-HCV prevalence among 101,727 adults entering prison was 18.1%. Prevalence was highest among those born from 1945 to 1965, but most anti-HCV cases were in people born after 1965. Targeted testing of the 1945 to 1965 birth cohort would have identified a decreasing proportion of cases with time. CONCLUSIONS: HCV is endemic in correctional populations. Targeted testing of the 1945 to 1965 birth cohort would produce a high yield of positive test results but would identify only a minority of cases. We recommend universal anti-HCV screening in correctional settings to allow for maximum case identification, secondary prevention, and treatment of affected prisoners.