All Publications

  • Stepped implementation-to-target: a study protocol of an adaptive trial to expand access to addiction medications. Implementation science : IS Ford, J. H., Cheng, H., Gassman, M., Fontaine, H., Garneau, H. C., Keith, R., Michael, E., McGovern, M. P. 2022; 17 (1): 64


    In response to the US opioid epidemic, significant national campaigns have been launched to expand access to `opioid use disorder (MOUD). While adoption has increased in general medical care settings, specialty addiction programs have lagged in both reach and adoption. Elevating the quality of implementation strategy, research requires more precise methods in tailoring strategies rather than a one-size-fits-all-approach, documenting participant engagement and fidelity to the delivery of the strategy, and conducting an economic analysis to inform decision making and policy. Research has yet to incorporate all three of these recommendations to address the challenges of implementing and sustaining MOUD in specialty addiction programs.This project seeks to recruit 72 specialty addiction programs in partnership with the Washington State Health Care Authority and employs a measurement-based stepped implementation-to-target approach within an adaptive trial design. Programs will be exposed to a sequence of implementation strategies of increasing intensity and cost: (1) enhanced monitoring and feedback (EMF), (2) 2-day workshop, and then, if outcome targets are not achieved, randomization to either internal facilitation or external facilitation. The study has three aims: (1) evaluate the sequential impact of implementation strategies on target outcomes, (2) examine contextual moderators and mediators of outcomes in response to the strategies, and (3) document and model costs per implementation strategy. Target outcomes are organized by the RE-AIM framework and the Addiction Care Cascade.This implementation project includes elements of a sequential multiple assignment randomized trial (SMART) design and a criterion-based design. An innovative and efficient approach, participating programs only receive the implementation strategies they need to achieve target outcomes. Findings have the potential to inform implementation research and provide key decision-makers with evidence on how to address the opioid epidemic at a systems level.This trial was registered at (NCT05343793) on April 25, 2022.

    View details for DOI 10.1186/s13012-022-01239-y

    View details for PubMedID 36175963

  • Expanding access to medications for opioid use disorder in primary care clinics: an evaluation of common implementation strategies and outcomes. Implementation science communications Cheng, H., McGovern, M. P., Garneau, H. C., Hurley, B., Fisher, T., Copeland, M., Almirall, D. 2022; 3 (1): 72


    BACKGROUND: To combat the opioid epidemic in the USA, unprecedented federal funding has been directed to states and territories to expand access to prevention, overdose rescue, and medications for opioid use disorder (MOUD). Similar to other states, California rapidly allocated these funds to increase reach and adoption of MOUD in safety-net, primary care settings such as Federally Qualified Health Centers. Typical of current real-world implementation endeavors, a package of four implementation strategies was offered to all clinics. The present study examines (i) the pre-post effect of the package of strategies, (ii) whether/how this effect differed between new (start-up) versus more established (scale-up) MOUD practices, and (iii) the effect of clinic engagement with each of the four implementation strategies.METHODS: Forty-one primary care clinics were offered access to four implementation strategies: (1) Enhanced Monitoring and Feedback, (2) Learning Collaboratives, (3) External Facilitation, and (4) Didactic Webinars. Using linear mixed effects models, RE-AIM guided outcomes of reach, adoption, and implementation quality were assessed at baseline and at 9 months follow-up.RESULTS: Of the 41 clinics, 25 (61%) were at MOUD start-up and 16 (39%) were at scale-up phases. Pre-post difference was observed for the primary outcome of percent of patient prescribed MOUD (reach) (betatime = 3.99; 0.73 to 7.26; p = 0.02). The largest magnitude of change occurred in implementation quality (ES = 0.68; 95% CI = 0.66 to 0.70). Baseline MOUD capability moderated the change in reach (start-ups 22.60%, 95% CI = 16.05 to 29.15; scale-ups -4.63%, 95% CI = -7.87 to -1.38). Improvement in adoption and implementation quality were moderately associated with early prescriber engagement in Learning Collaboratives (adoption: ES = 0.61; 95% CI = 0.25 to 0.96; implementation quality: ES = 0.55; 95% CI = 0.41 to 0.69). Improvement in adoption was also associated with early prescriber engagement in Didactic Webinars (adoption: ES = 0.61; 95% CI = 0.20 to 1.05).CONCLUSIONS: Rather than providing an all-clinics-get-all-components package of implementation strategies, these data suggest that it may be more efficient and effective to tailor the provision of implementation strategies based on the needs of clinic. Future implementation endeavors could benefit from (i) greater precision in the provision of implementation strategies based on contextual determinants, and (ii) the inclusion of strategies targeting engagement.

    View details for DOI 10.1186/s43058-022-00306-1

    View details for PubMedID 35794653

  • A mapping review of NIDA-funded implementation research studies on treatments for opioid and/or stimulant use disorders. Drug and alcohol dependence Cheng, H., Chokron Garneau, H., Yuan, M., McGovern, M. P. 2021; 225: 108767


    BACKGROUND: The biomedical research enterprise invests greatly in discovery-oriented science, but significantly less in how to implement the most effective of these innovations. The return on investment in public health benefit is therefore low. In the context of substance-related overdose epidemics, presently with opioids and/or stimulants, the gap in proven treatments and routine access is amplified. Implementation research is designed to deepen understanding of how best to scale-up proven treatments. This study assessed how implementation research has been deployed in the National Institute on Drug Abuse (NIDA) efforts to address the opioid and stimulant epidemics.METHODS: Adapting a procedure developed to categorize HIV-focused research, a four-stage systematic mapping review of NIDA-funded R01, R34, R61, and U studies pertaining to opioids and/or stimulants funded between 2015 and 2019 was performed. Abstracts were retrieved using NIH Research Portfolio Online Reporting Tools. Key study characteristics were abstracted and coded by two independent reviewers.RESULTS: An initial search across NIH institutes yielded 5963 relevant records. Of these, 666 (11.2 %) were NIDA funded. One-hundred-and-thirty-four (20.1 %) of the 666 studies were opioid and/or stimulant treatment related. Of these, 28 (4.2 %) were categorized as Implementation Preparation (IP), and 16 (2.4 %) were categorized as Implementation Research (IR). Over the five-year period, there was a gradual increase in both IP and IR studies.CONCLUSIONS: Implementation research is a small but slowly growing component of the federal portfolio to address substance-related public health issues. To more effectively respond to contemporary overdose epidemics, implementation research must take on an even more significant role.

    View details for DOI 10.1016/j.drugalcdep.2021.108767

    View details for PubMedID 34052689

  • Patient and provider perspectives of personal health record use: a multisite qualitative study in HIV care settings. Translational behavioral medicine Conti, J., Fix, G. M., Javier, S. J., Cheng, H., Perez, T., Dunlap, S., McInnes, D. K., Midboe, A. M. 2023


    Use of tethered personal health records (PHRs) can streamline care, reduce unnecessary care utilization, and improve health outcomes for people living with human immunodeficiency virus (HIV). Providers play a role in influencing patients' decision to adopt and use PHRs. To explore patient and provider acceptance and use of PHRs in an HIV care setting. We used a qualitative study design guided by the Unified Theory of Acceptance and Use of Technology. Participants included providers of HIV care, patients living with HIV, and PHR coordinating and support staff in the Veterans Health Administration (VA). Interviews were analyzed using directed content analysis. We interviewed providers (n = 41), patients living with HIV (n = 60), and PHR coordinating and support staff (n = 16) at six VA Medical Centers between June and December 2019. Providers perceived PHR use could enhance care continuity, appointment efficiency, and patient engagement. Yet, some expressed concerns that patient PHR use would increase provider workload and detract from clinical care. Concerns about poor PHR interoperability with existing clinical tools further eroded acceptance and use of PHRs. PHR use can enhance care for patients with HIV and other complex, chronic conditions. Negative provider attitudes toward PHRs may impact providers' encouragement of use among patients, consequently limiting patient uptake. Multipronged interventions at the individual, institutional, and system level are needed to enhance PHR engagement among both providers and patients.

    View details for DOI 10.1093/tbm/ibac118

    View details for PubMedID 37084300

  • A scoping review of implementation of health-focused interventions in vulnerable populations. Translational behavioral medicine Daniels, S. I., Cheng, H., Gray, C., Kim, B., Stave, C. D., Midboe, A. M. 2022; 12 (9): 935-944


    Vulnerable populations face significant challenges in getting the healthcare they need. A growing body of implementation science literature has examined factors, including facilitators and barriers, relevant to accessing healthcare in these populations. The purpose of this scoping review was to identify themes relevant for improving implementation of healthcare practices and programs for vulnerable populations. This scoping review relied on the methodological framework set forth by Arksey and O'Malley, and the Consolidated Framework for Implementation Research (CFIR) to evaluate and structure our findings. A framework analytic approach was used to code studies. Of the five CFIR Domains, the Inner Setting and Outer Setting were the most frequently examined in the 81 studies included. Themes that were pertinent to each domain are as follows-Inner Setting: organizational culture, leadership engagement, and integration of the intervention; Outer Setting: networks, external policies, and patients' needs and resources; Characteristics of the Individual: knowledge and beliefs about the intervention, self-efficacy, as well as stigma (i.e., other attributes); Intervention Characteristics: complexities with staffing, cost, and adaptations; and Process: staff and patient engagement, planning, and ongoing reflection and evaluation. Key themes, including barriers and facilitators, are highlighted here as relevant to implementation of practices for vulnerable populations. These findings can inform tailoring of implementation strategies and health policies for vulnerable populations, thereby supporting more equitable healthcare.

    View details for DOI 10.1093/tbm/ibac025

    View details for PubMedID 36205470

  • Social Support is Associated with Survival in Patients Diagnosed with Gastrointestinal Cancer JOURNAL OF GASTROINTESTINAL CANCER Bou-Samra, P., Scott, P., Cheng, H., Kallem, C., Pathak, R., Geller, D. A., Marsh, W., Wang, Y., Antoni, M., Penedo, F., Tsung, A., Steel, J. L. 2021


    The aim of this study was to examine the link between psychological, behavioral, and social factors and survival in patients diagnosed with gastrointestinal cancer.A cohort of gastrointestinal cancer patients were administered a battery of questionnaires that assessed trauma, depression, social support, sleep, diet, exercise, quality of life, tobacco and alcohol use, pain, and fatigue. Analyses included Pearson's correlations, analyses of variance, Kaplan Meier survival, and Cox regression analyses.Of the 568 patients, the majority were male (57.9%) and Caucasian (91.9%), with a mean age of 61 (S.D. = 10.7). The level of perceived social support was comparable to patients with other medical conditions. Sociodemographic predictors of social support included the number of years of education (r = 0.109, p = 0.05), marital status (F(6,387) = 5.465, p ≤ 0.001), and whether the patients' income met the family's basic needs (F(1,377) = 25.531, p < 0.001). Univariate analyses revealed that older age (p < 0.001), male gender (p = 0.007), being black (p = 0.005), diagnosis of hepatocellular carcinoma (p = 0.046), higher body mass index (p = 0.022), larger tumor size (p = 0.032), initial treatment including chemotherapy rather than surgery (p < 0.001), and lower level of perceived social support (p = 0.037) were associated with poorer survival. Using multivariate Cox regression and adjusting for all factors found to be significant in univariate survival analyses, older age (p = 0.024) and lower perceived social support (HR = 0.441, 95% CI = 0.233, 0.833; p = 0.012) were the factors that remained significantly associated with poorer survival.There are several biological and psychosocial factors that predict cancer mortality. Social support appears to be a robust factor affecting mortality in gastrointestinal cancer patients.

    View details for DOI 10.1007/s12029-021-00741-8

    View details for Web of Science ID 000720805000001

    View details for PubMedID 34806126

  • The Integrating Medications for Addiction Treatment (IMAT) Index: A measure of capability at the organizational level. Journal of substance abuse treatment Chokron Garneau, H., Hurley, B., Fisher, T., Newman, S., Copeland, M., Caton, L., Cheng, H., McGovern, M. P. 2021; 126: 108395


    Primary care provides a treatment opportunity for many persons with opioid use disorder (OUD). The push to integrate and expand reach and adoption of medications for opioid use disorder (MOUD) within primary care has been a major focus of national, state and health systems endeavors. To guide high capability MOUD practice, we introduce the Integrating Medications for Addiction Treatment (IMAT) Index. The research team has developed IMAT along similar lines to other organizational measures of integrated services capability. We present the development and validation of the measure, and suggest its applicability for systems and organizations, as well as for process improvement and implementation research. Forty-one primary care clinics completed the IMAT at two time points: baseline and 9-month follow-up. Findings support the IMAT Index as psychometrically acceptable and pragmatically useful. It has good internal consistency, as well as concurrent and predictive validity. Changes in IMAT scores between baseline and follow-up significantly predicted increases in proportion of patients on MOUD. The IMAT has the potential to support both scientific and public health care activities.

    View details for DOI 10.1016/j.jsat.2021.108395

    View details for PubMedID 34116810

  • COVID-19 Adaptations in the Care of Patients with Opioid Use Disorder: a Survey of California Primary Care Clinics. Journal of general internal medicine Caton, L. n., Cheng, H. n., Garneau, H. C., Fisher, T. n., Harris-Mills, B. n., Hurley, B. n., Newman, S. n., McGovern, M. P. 2021


    With the onset of the COVID-19 crisis, many federal agencies relaxed policies regulating opioid use disorder treatment. The impact of these changes has been minimally documented. The abrupt nature of these shifts provides a naturalistic opportunity to examine adaptations for opioid use disorder treatment in primary care.To examine change in medical and behavioral health appointment frequency, visit type, and management of patients with opioid use disorder in response to COVID-19.A 14-item survey queried primary care practices that were enrolled in a medications for opioid use disorder statewide expansion project. Survey content focused on changes in service delivery because of COVID-19. The survey was open for 18 days.We surveyed 338 clinicians from 57 primary care clinics located in California, including federally qualified health centers and look-alikes. A representative from all 57 clinics (100%) and 118 staff (34.8% of all staff clinicians) participated in the survey.The survey consisted of seven dimensions of practice: medical visits, behavioral health visits, medication management, urine drug screenings, workflow, perceived patient demand, and staff experience.A total of 52 of 57 (91.2%) primary care clinics reported practice adaptations in response to COVID-19 regulatory changes. Many clinics indicated that both medical (40.4%) and behavioral health visits (53.8%) were now exclusively virtual. Two-thirds (65.4%) of clinics reported increased duration of buprenorphine prescriptions and reduced urine drug screenings (67.3%). The majority (56.1%) of clinics experienced an increase in patient demand for behavioral health services. Over half (56.2%) of clinics described having an easier or unchanged experience retaining patients in care.Many adaptations in the primary care approach to patients with opioid use disorder may be temporary reactions to COVID-19. Further evaluation of the impact of these adaptations on patient outcomes is needed to determine whether changes should be maintained post-COVID-19.

    View details for DOI 10.1007/s11606-020-06436-3

    View details for PubMedID 33511572

  • Sleep problems in advanced cancer patients and their caregivers: Who is disturbing whom? JOURNAL OF BEHAVIORAL MEDICINE Chen, Q., Terhorst, L., Lowery-Allison, A., Cheng, H., Tsung, A., Layshock, M., Buysse, D. J., Geller, D. A., Marsh, J. W., Wang, Y., Steel, J. L. 2020; 43 (4): 614-622


    Background The aims of the study were to understand sleep problems and their effects in advanced cancer patients and spousal and intimate partner caregivers and to examine the directionality of the link between patients' and caregivers' sleep problems. Methods Fifty-four advanced cancer patients and their spousal and intimate partners were administered a battery of questionnaires that included the Pittsburgh Sleep Quality Index and the Center for Epidemiological Studies at the patients' cancer diagnosis and at 2, 4, and 6 months after diagnosis. Results Patients' and caregivers' sleep duration was significantly related. Using cross-lagged panel analyses, caregivers' sleep quality significantly predicted patients' sleep quality and patients' sleep quality subsequently predicted caregivers' sleep quality. Patients' sleep latency significantly was found to significantly predict caregivers' sleep latency. Conclusion Patients diagnosed with cancer and their intimate partners have poor sleep quality and sleep patterns are related.

    View details for DOI 10.1007/s10865-019-00088-3

    View details for Web of Science ID 000549600000010

    View details for PubMedID 31435891

    View details for PubMedCentralID PMC7035154

  • Implementation of health-focused interventions in vulnerable populations: protocol for a scoping review. BMJ open Midboe, A. M., Gray, C., Cheng, H., Okwara, L., Gale, R. C. 2020; 10 (7): e036937


    INTRODUCTION: Vulnerable populations face significant challenges in navigating the care continuum, ranging from diagnosis of illness to linkage and retention in healthcare. Understanding how best to move individuals within these vulnerable populations across the care continuum is critical to improving their health. A large body of literature has focused on evaluation of implementation of various health-focused interventions in this population. However, we do not fully understand the unique challenges to implementing healthcare interventions for vulnerable populations. This study aims to examine the literature describing implementation of health service interventions among vulnerable populations to identify how implementations using the Consolidated Framework for Implementation Research are adapted. Findings from this review will be useful to implementation scientists to identify gaps in evidence and for adapting similar interventions in unique settings.METHODS AND ANALYSIS: This study protocol outlines a scoping review of the peer-reviewed and grey literature, using established approaches delineated in Arksey and O'Malley's scoping review framework and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews Checklist. Search strategies will be developed and refined by a medical librarian in collaboration with the research team. Searches will be conducted in electronic databases (CINAHL, Cochrane, PsychINFO, PubMed, Social Services Abstracts, Web of Science, Google and Google Scholar) and limited to studies published between 1 August 2009 and 1 June 2020. Additionally, hand searches will be conducted in three relevant journals-Implementation Science, Systematic Reviews and BMJ Open. English-language studies and reports meeting inclusion criteria will be screened independently by two reviewers and the final list will be abstracted and charted in duplicate.ETHICS AND DISSEMINATION: This is a review of the literature; ethics approval is not indicated. We will disseminate findings from this study in peer-reviewed journals as well as presentations to relevant stakeholders and conferences.

    View details for DOI 10.1136/bmjopen-2020-036937

    View details for PubMedID 32690530

  • Socioeconomic disparities of depressive symptoms and cytokines in hepatocellular carcinoma PSYCHO-ONCOLOGY Cheng, H. H., Kamarck, T. W., Gianaros, P. J., Roecklein, K. A., Vanegas, Y., Tsung, A., Geller, D. A., Marsh, J. W., Ahmed, N. S., Steel, J. L. 2019; 28 (8): 1624-1632


    To examine the associations among socioeconomic factors, depressive symptoms, and cytokines in patients diagnosed with hepatocellular carcinoma (HCC).A total of 266 patients diagnosed with HCC were administered a battery of questionnaires including a sociodemographic questionnaire and the Center for Epidemiologic StudiesDepression (CES-D) scale. Blood samples were collected to assess serum levels of cytokines using Luminex. Descriptive statistics, Mann-Whitney U, Kruskal-Wallis, linear regression, and Bonferroni corrections were performed to test the hypotheses.Of the 266 patients, 24% reported depressive symptoms in the clinical range (CES-D ≥ 22). Females had higher CES-D score than males (Mann-Whitney U = 7135, P = .014, Padj  = .028). Being unemployed/disabled (Kruskal-Wallis = 14.732, P = .001, Padj  = .005) was found to be associated with higher depressive symptoms in males but not in females. Serum level of IL-2 (Kruskal-Wallis = 17.261, P = .001, Padj  = .005) were found to be negatively associated with education level. Gender (β = .177, P = .035), income (β = -.252, P = .004), whether the patient's income met their basic needs (β = .180, P = .035), and IL-1β (β = -.165, P = .045) independently predicted depressive symptoms and together explained 19.4% of variance associated with depressive symptoms.Sociodemographic and socioeconomic factors were predictive of inflammation and depressive symptoms. Recommendations include the development of gender-targeted interventions for patients diagnosed with HCC who have low socioeconomic status (SES) and may suffer from depressive symptoms.

    View details for DOI 10.1002/pon.5127

    View details for Web of Science ID 000478101300004

    View details for PubMedID 31119824

    View details for PubMedCentralID PMC7241307

  • Psychosocial and behavioral pathways of metabolic syndrome in cancer caregivers PSYCHO-ONCOLOGY Steel, J. L., Cheng, H., Pathak, R., Wang, Y., Miceli, J., Hecht, C., Haggerty, D., Peddada, S., Geller, D. A., Marsh, W., Antoni, M., Jones, R., Kamarck, T., Tsung, A. 2019; 28 (8): 1735-1742


    Cancer caregivers are at increased risk for cardiovascular disease (CVD) and mortality. The aims of this study were to examine psychosocial and behavioral predictors of metabolic syndrome, an intermediate endpoint of CVD.Cancer caregivers were administered a battery of questionnaires assessing sociodemographic characteristics, depressive symptoms, perceived stress, caregiver quality of life, sleep, physical activity, alcohol and tobacco use, social support, relationship quality, and loneliness. Metabolic syndrome was defined using the American Heart Association guidelines and the National Cholesterol Education Program's Adult Treatment Panel (ATP) III, which includes the presence of at least three of the following abnormalities: blood pressure, glucose, abdominal girth, high-density lipoprotein (HDL), and triglycerides.Of the 104 caregivers, 77% were female, 94% were Caucasian, and the mean age was 59.5 (SD = 12.8). Of the 104 caregivers, 35.6% reported depressive symptoms in the clinical range of the Center for Epidemiologic Studies-Depression (CES-D) and 69.2% reported Perceived Stress Scale scores at least one standard deviation above the general population norms. A total of 16.3% of caregivers currently used tobacco, 28.8% consumed alcohol, and 26.7% were overweight (BMI = 25-29.9) and 48.5% were obese (BMI ≥ 30). Forty-nine percent of the caregivers met the criteria for metabolic syndrome. After age, gender, and race were adjusted, the following remained as significant predictors of metabolic syndrome: low levels of caregiver quality of life (Odds Ratio (OR) = 1.067; 95% CI, 1.019-1.117; P = .006), high levels of hostility (OR = 1.142; 95% CI, 1.030-1.267; P = .012), and current alcohol use (OR = 4.193; 95% CI, 1.174-14.978; P = .027).Development of interventions to reduce the risk of metabolic syndrome in cancer caregivers is recommended.

    View details for DOI 10.1002/pon.5147

    View details for Web of Science ID 000478101300018

    View details for PubMedID 31206896

    View details for PubMedCentralID PMC6768062

  • Illness perceptions and perceived stress in patients with advanced gastrointestinal cancer PSYCHO-ONCOLOGY Miceli, J., Geller, D., Tsung, A., Hecht, C., Wang, Y., Pathak, R., Cheng, H., Marsh, W., Antoni, M., Penedo, F., Burke, L., Ell, K., Shen, S., Steel, J. 2019; 28 (7): 1513-1519


    According to the Common-Sense Model of Self-Regulation, when faced with a health threat, we make cognitive and emotional assumptions about the illness. The aims of this study were to (a) examine the role of sociodemographic and disease-specific factors on illness perception and perceived stress and (b) test the association between perceived stress and illness perception in participants diagnosed with gastrointestinal cancer.Participants completed a battery of questionnaires including a Sociodemographic and Disease-Specific Questionnaire, the Illness Perception Questionnaire, Brief Version (Brief-IPQ), and the Perceived Stress Scale (PSS-14). Descriptive statistics, Pearson correlations, analysis of variance (ANOVA), and linear regression were performed to test the hypotheses.Of the 627 participants, the mean age was 62 years (SD = 11); the majority were male (63.3%) and Caucasian (90.9%). Younger (F3,625 = 5.80, P < .01) and divorced or never married participants reported higher levels of perceived stress when compared with older and married participants (F4,618 = 3.52, P < .01). Younger participants (18-74 years old) reported more negative illness perceptions than older participants (75 years and older) (F3,511 = 4.08, P < .01). A weak, positive relationship between perceived stress and illness perceptions was observed (r = 0.22, P < .01), and illness perceptions predicted 36.1% of the variance of perceived stress.Our findings suggest that participants who negatively perceived their illness experienced greater levels of perceived stress. Interventions that aim to adjust patients' illness perceptions in order to facilitate a reduction of stress and improvement in quality of life are needed.

    View details for DOI 10.1002/pon.5108

    View details for Web of Science ID 000474293000019

    View details for PubMedID 31090125

    View details for PubMedCentralID PMC6610754

  • Broad-spectrum non-nucleoside inhibitors of human herpesviruses ANTIVIRAL RESEARCH McClain, L., Zhi, Y., Cheng, H., Ghosh, A., Piazza, P., Yee, M. B., Kumar, S., Milosevic, J., Bloom, D. C., Arav-Boger, R., Kinchington, P. R., Yolken, R., Nimgaonkar, V., D'Aiuto, L. 2015; 121: 16-23


    Herpesvirus infections cause considerable morbidity and mortality through lifelong recurrent cycles of lytic and latent infection in several tissues, including the human nervous system. Acyclovir (ACV) and its prodrug, the current antivirals of choice for herpes simplex virus (HSV) and, to some extent, varicella zoster virus (VZV) infections are nucleoside analogues that inhibit viral DNA replication. Rising viral resistance and the need for more effective second-line drugs have motivated searches for additional antiviral agents, particularly non-nucleoside based agents. We evaluated the antiviral activity of five compounds with predicted lysosomotropic activity using conventional and human induced pluripotent stem cell-derived neuronal (iPSC-neurons) cultures. Their potency and toxicity were compared with ACV and the lysosomotropic agents chloroquine and bafilomycin A1. Out of five compounds tested, micromolar concentrations of 30N12, 16F19, and 4F17 showed antiviral activity comparable to ACV (50μM) during lytic herpes simplex virus type 1 (HSV-1) infections, reduced viral DNA copy number, and reduced selected HSV-1 protein levels. These compounds also inhibited the reactivation of 'quiescent' HSV-1 infection established in iPSC-neurons, but did not inhibit viral entry into host cells. The same compounds had greater potency than ACV against lytic VZV infection; they also inhibited replication of human cytomegalovirus. The anti-herpetic effects of these non-nucleoside agents merit further evaluation in vivo.

    View details for DOI 10.1016/j.antiviral.2015.06.005

    View details for Web of Science ID 000360511500003

    View details for PubMedID 26079681

    View details for PubMedCentralID PMC4536133