Early-career research education mentoring: a successful program in NeuroHIV and mental health (TRNAMH)

40-years: an evolving landscape of HIV-associated neurological complications

Understanding the detrimental impacts of HIV infection on the nervous system has been a major research focus since the virus was identified in the late 1980s. Forty years ago, people presenting with clinical symptoms, including severe subcortical cognitive impairment, movement disorders, typically bradykinesia, and gait abnormalities with or without behavioral symptoms, were diagnosed with acquired immune deficiency syndrome (AIDS) dementia complex (ADC). ADC became the first described and clinically used definition of AIDS [1–3] (Figure 1). It was also recognized that HIV affected the spinal cord resulting in a vacuolar myelopathy and peripheral nerve small fiber neuropathy with several scientists at Johns Hopkins contributing to seminal findings to the latter [4–8]. In the decades since the start of the HIV pandemic, scientific innovations in testing, treatment, and management built upon key biologic insights and understanding gained from basic and clinical research, have improved the well-being and life expectancy of millions of people worldwide living with the infection [9–12]. First described in the 1980s through mid-1990s [13–15], understanding of the neurological complications of HIV infection covered a broad range of topics in the life sciences and medical specialties, including neurology/neuroscience, psychiatry/behavior, immunology/infectious disease, and pharmacology.

Figure 1:

Timeline of the HIV epidemic and notable landmark advances, events and resources related to HIV neurologic complications. HIV-1, human immunodeficiency virus; AIDS, acquired immunodeficiency syndrome; CHARTER, CNS HIV anti-retroviral therapy effects research; HAND, HIV-associated neurocognitive disorders; U=U, undetectable=untransmissible; COVID-19, SARS Co-V 2 coronavirus disease; AZT, azidothymidine.

A consensus about how the neurological impacts of HIV infection of the brain should be identified and classified was reached in 2007 [16]. The designation of “HAND” for “HIV-associated neurologic disorders” was coined and provided a research framework for assessment. A determination of HAND requires the use of a battery of neuropsychological tests, assessments to measure daily living, and clinical evaluations to identify whether and to what extent an individual’s cognitive and motor functions differ from the norm [17, 18]. More recently, the field has moved toward embracing the shift away from the Diagnostic and Statistical Manual of Mental Disorders (DSM) classification system to the Research Domain Criteria (RDoC). RDoC aims to better account for the intricate linkages between disorder presentation and the associated varied biological variables [19]. Saving lives and mitigating the worldwide impact of HIV required simultaneous action and collaboration between clinical and basic science research enterprises [20–23]. Therefore, irrespective of the specific research focus of individual participants, understanding the overall clinical presentation and how people with HIV are identified as suffering from neurological complications was, as described below, a central component of the didactic training component.

Figure 1 shows the timeline of what became an HIV pandemic that spread across countries and borders and evolved into the current ongoing epidemic superimposed with select landmark advances in research, clinical care, and policy. While the United States President’s Plan for AIDS Relief (PEPFAR) funds that support infrastructure and antiviral treatment continue to have a great impact in reducing the spread of the virus, upticks in HIV infection in times of civil unrest, famine, or other disease outbreaks remains a challenge [24, 25]. In the United States, the value of well-characterized cohorts of people with HIV (PWH) such as the NIH-funded Multicenter AIDS Cohort Study (MACS) developed in 1984, and the Women’s Interagency HIV Study (WIHS) initiated in 1993, have contributed significantly to the existing knowledge of HIV neuropathology and clinical outcomes. Today, the two function in a synergistic manner as the “MACS/WIHS Combined Cohort Study” [26–28]. The CNS HIV Antiretroviral Therapy Effects Research (CHARTER), established in 2002 and expanded in 2015, later incorporated the tissue and data management coordinating centers of The National NeuroAIDS Tissue and Consortium (NNTC) and its associated data center [29, 30]. Coincident with further advances in regimens, such as fewer pills involved in combined ART (cART), reduced side effects, and the addition of antiretroviral drugs targeting discrete stages of the HIV replication cycle, came additional improvements in neuropsychiatric outcomes, as well as life-expectancy for people with HIV [17, 31], [32], [33]. At Johns Hopkins, a dedicated program to conduct research into neuroHIV, the Northeastern AIDS Dementia Consortium (NEAD) was created in 1998 and marked the founding of the current Division of Neuroimmunology and Neurovirological Infections [34].

In developed countries, advances in HIV research and treatment success have translated into the reality of millions of people aging with HIV. However, without a cure or vaccine, many experience comorbid conditions including cardiovascular and kidney disease, chronic obstructive pulmonary disorder, osteoporosis, frailty, and the continuous threat of lung, breast, colon, and other types of cancers [9, 35], [36], [37]. To reflect this data-driven understanding of HIV neuropathogenesis, in 2018, we began to use the term “NeuroHIV or neuroHIV” instead of “NeuroAIDS”. We will use the former notation in this paper hereafter.

Goal of TRNAMH: nurture a well-trained, resilient, and diverse neuroscience and mental health biomedical research workforce

A properly trained biomedical workforce is required to ensure the USA’s leadership in innovative, high-impact research that benefits the well-being of society. Therefore, educational programming at the graduate level and beyond, which features high-quality training, mentorship, and skill-building in the mechanics of applying for research grants, is essential to advance these goals. Promoting diversity in research has been a stated goal for NIH-funded research institutions since the inception of the Minority Health Initiative in 1992 [38]. Data has continued to accrue which demonstrates that investing in training a more diverse biomedical research workforce, particularly by providing expanded access and support to trainees from URMs and/or those with disabilities, improved matriculation rates into STEM (science, technology, engineering, and mathematics) fields, and leads to more productive and skilled scientific researchers [39, 40]. While the percentage of incoming URM graduate student enrollees in any STEM field has increased on average by 8.4 % between 2011 and 2021 [41], representation in the neurosciences and psychiatric fields at the doctoral level has only increased by about 3.9 % on average in a similar time frame, between 2005 and 2015 [42]. Statistics showed that despite national efforts to encourage and support increased recruitment of diverse, underrepresented minority groups into advanced degree programs and faculty academic research positions in the neurosciences, between 1995 and 2015, doctoral degree recipients in neuroscience comprised only 2.77 % Black/African-Americans, 9.4 % Asian/Pacific Islanders, and 4.3 % Hispanics [42], while more than 70 % were Whites or Asians [43, 44]. These numbers for the URM neuroscience graduates are far below the representation of these groups in the overall US population or even in the pool of URMs who express motivation and aptitude for a career in STEM but later exit from the pipeline [45]. Many studies established that challenges to retention in STEM for women and URMs are associated with the institutional environments and cultures which are often unwelcoming and disaffirming [46].

The premise on which the TRNAMH program was built is that a highly-qualified pool of diverse talent exists and that if given the proper professional support, retention, and advancement in the field will be effectively promoted. The primary aims of the TRNAMH program were to provide mentorship, didactic training, and research support to early-career doctoral students, post-doctoral trainees, and junior faculty with emphasis on those from racial and ethnic URM groups with basic and clinical research interests in the neuroHIV field. The long-term goals were to strengthen foundational skills and knowledge of the neurological and immunological impacts of HIV infection through additional targeted initiatives that included research ethics, grant writing practice, and mentoring, to further promote career development and research independence. Recent critical analyses of evidence-based practices and an understanding of the competencies required for a well-trained neuroscience workforce lend support for the TRNAMH program’s overall design [47].

Component I. Evolution and outcomes of the multidisciplinary didactic course from 2007 to 2019

The training program was originally conceived and developed in 2006 by Dr. Avindra Nath, MD, and co-directed with Dr. Amanda Brown, PhD, with R25 funding from the NIMH (R25 MH080661) [48]. Of note, the program was initially named Diversity-Related Neuro-AIDS and Mental Health Research and was changed in subsequent funding periods to its current name: Translational Research in NeuroHIV and Mental Health (TRNAMH). The first cohort of trainees began in August 2007, and the final didactic course ended in December 2019. The course emphasized and encouraged a solid foundation in both basic and clinical aspects of neurology, pharmacology, behavioral sciences, psychiatry, epidemiology, and immunology, selecting candidates with an interest in interdisciplinary research into the detection, treatment, and understanding of the various neurobiological and functional outcomes of HIV infection and HAND. Originally, the program was conceived as an institutional collaboration between faculty at the Johns Hopkins School of Medicine, the University of Hawaii at Manoa, and the University of Puerto Rico, Medical Sciences Campus. As the program grew in popularity, additional support and voluntary contributions of time and effort from faculty lecturers and mentors at many more partnering institutions were added and included the: University of California San Diego, University of Nebraska, Temple University, Virginia Commonwealth University, Ponce School of Medicine, Universidad del Caribe, University of Honolulu, Lehigh University, Boston University, Washington University, Drexel University, Hampton University, University of Kentucky, and Georgetown University.

While most program participants possessed a degree of knowledge in the NeuroHIV field, a small percentage was always new by transitioning to graduate school or through an interdisciplinary research collaboration. In this context, the didactic portion of the program always began with a historical clinical and epidemiologic overview followed by a discussion of the latest research findings in neuroHIV. In this regard, and given the availability of the human brain and other organ tissues and body fluids available through the NNTC, CHARTER, ACTG, and NEAD, a complete understanding of these resources is critical for the neuroHIV researcher. At its inception, the coursework was designed to first cover the basic virology and neuropathogenesis of HIV and continue through an examination of the translational and clinical aspects of neuroHIV research and how HAND is treated. Coursework also included key topics on the role of race and ethnicity, cultural sensitivity, the importance of translatability in data collection tools for different populations, and ethics in research.

The course had several unique forward-thinking aspects that contributed to its success. Several of the courses were taught by URM faculty. Course discussions addressed access to and equity in clinical trials many years before (the recent increased attention to this topic [44, 49, 50]). The course embraced a webinar format from its inception as its main mode of teaching and communication long before Skype, Zoom, and other virtual platforms were developed. However, as these newer technologies emerged, the course quickly adopted their use. Importantly, this provided expanded access to both trainees and neuroHIV experts from across the continental USA, Hawaii, and Puerto Rico to join in discussions, didactic teaching, and journal clubs at no cost. Thus, the TRNAMH program was a pioneer in overcoming several institutional and logistical challenges of pre-COVID-19 era traditional teaching formats. In this manner, the course provided mentorship to the trainees, helped them develop research projects, provided pilot funds to select individuals on a competitive basis, and developed lasting relationships with the trainees despite being separated over far geographic distances. This type of investment in the careers of the students was unprecedented and represents a model for other teaching courses and institutions.

Course participant demographics

Trainees in our program who identified as Asian were predominantly of Indian or Chinese ethnicity. Among our Black/African-American trainees, all of our cohort participants were African-American. We did not have any trainees who identified as Native American/Alaskan Native. While there were significant differences in the number of participants from each racial/ethnic group, over the 12 years, 41 % of trainees came from URM groups (Tables 1–3, Figure 2a). One-way ANOVA analysis of the 5 racial groupings represented in our cohort showed that the proportion of trainees enrolled from each of the defined racial groups (determined by self-report) varied significantly by group from year to year (F (4,55)=11.56, p<0.0001). While the enrollment of those from Asian and Pacific Islander backgrounds was stable, that of Black/African-Americans generally rose each year, and that of Hispanics which began with robust participation that held steady for seven cycles fell off sharply in the later years (Table 1 Graph). The latter can be partially attributed to the detrimental impacts on research infrastructure in Puerto Rico from Hurricane Maria in 2017. The proportion of trainees varied at different career stages with 41 % pre-doctoral, 31 % post-doctoral, 21 % early-career (e.g., research associate, assistant professor), 5 % professor, and 2 % non-degree (other) (Figure 2b).

Table 1 and Graph:

Demographic characteristics of TRNAMH course trainees by year, 2007–2019.

1. The TRNAMH program did not run in 2015, as grant fund renewal was pending. The graph shows the data in Tables 1–4 in a longitudinal manner to show trends in enrollment.

Figure 2:

Total racial/ethnic representation (a) and career level (b) of TRNAMH trainees 2007–2019. URM includes the following racial and ethnic groups shown to be underrepresented in biomedical research: Black/African Americans (Black/AA), Hispanics or Latinos, American Indians or Alaska Natives, Native Hawaiians, and other Pacific Islanders.” https://diversity.nih.gov/about-us/population-underrepresented.

As part of the core of the program, all participants completed 12 weekly formal didactic lectures. Topics of instruction were administered by experts in their respective fields and included the clinical epidemiology of HIV in the nervous system, neuroimaging, neuropathology of HIV, in vitro and in vivo disease models, genetics, cognitive and clinical neurological assessment, grant funding advice, as well as the role that racial and ethnic disparities play in study design, ethics, access to care, and representation in the medical and biological sciences (see TRNAMH Course topics, Table 2). Trainees concurrently enrolled at Johns Hopkins University could enroll in the course for 1.5 academic credits with advance notice. Remote trainees could register to receive academic course credits at their home institutions if the courses were approved or they could audit the course for free. NIH grant funding for this program also allowed for tuition remission for those seeking academic credits and who qualified as a trainee from a URM group. The majority of participants chose to audit the course instead of receiving college credit.

Table 2:

Didactic syllabus for translational research in NeuroHIV and mental health (TRNAMH) course, 2007–2019. The table shows the faculty lead discussants and their associated academic institutions. Darker shading indicates new courses that were added in 2014 to make a 16-week course from 2014 to 2019.

Course topics: 12-weeks (2007–2013) and 16-weeks (2014–2019)	Faculty instructor(s)	Institution(s)
1. Course overview and clinical epidemiology of HAND	Amanda Brown, PhD Ned Sacktor, MD	Johns Hopkins University
2. Intro to retroviruses and pathology of NeuroHIV	Vivek Nerurkar, PhD Carlos Pardo, MD	University of Hawaii, Manoa Johns Hopkins University
3. Cultural sensitivity in neuropsychological scales for HAND/Ethics in NeuroHIV research	Valerie Wojna, MD Bruce Shiramizu, MD	University of Puerto Rico, Medical Sciences Campus University of Hawaii, Manoa
4. Neuropathogenics of HIV infection and IRIS	Avindra Nath, MD	National Institute of Neurological Disorders and Stroke
5. Viral genetics and cellular reservoirs	Janice Clements, PhD Joseph Mankowski, DVM, PhD	Johns Hopkins University
6. Drugs of abuse in HAND	Shilpa Buch, PhD Kurt Hauser, PhD	University of Nebraska Virginia Commonwealth University
7. Surrogate and host genetic markers	Norman Haughey, PhD	Johns Hopkins University
8. Blood-brain barrier and HIV	Monique Stins, PhD	Johns Hopkins University
9. CNS penetration, HIV-1 replication and combination anti-retroviral therapies	Scott Letendre, MD	University of California, San Diego
10. Rodent models and behavioral assessment	Mikhail Pletnikov, MD, PhD Amanda Brown, PhD	Johns Hopkins University
11. Drug development for HAND	Joseph Steiner, PhD Takashi Tsukamoto, PhD	National Institute of Neurological Disorders and Stroke Johns Hopkins University
12. Imaging techniques in NeuroHIV	Beau Ances, MD, PhD Linda Chiang, MD	Washington University in St. Louis University of Maryland School of Medicine
13. Clinical research techniques and how to get and Stay funded	Justin McArthur, MBBS, MPH	Johns Hopkins University
14. Cardiovascular disease in HIV	Tricia Burdo, PhD	Temple University
15. Sleep and HIV/App development	Charlene Gamaldo, MD Rachel Salas, MD Peter Dziedzic, MS	Johns Hopkins University
16. The wear and tear of stress on cognition in HIV	Leah Rubin, PhD, MPH	Johns Hopkins University

Between 2007 and 2009, the 12-week course was offered via webcast videoconferencing, which was at the time considered state-of-the-art technology. Feedback from trainees in these years suggested that while convenient for the different time zones, the webcast format provided limited interactive value with their fellow students and course faculty due to system limitations, glitching, and difficulty in setting up the system using a combination of computers and phone lines. In response to these suggestions, TRNAMH began testing and adopting the use of other interactive web-conferencing platforms, including Adobe Connect and Zoom, which were adopted in 2018 for use in 2019. The platform proved easy to use for the administrators and students in the course, allowing the program to successfully connect with a large cohort of students from across the US and internationally. The format allowed students from anywhere in the country to actively engage in live discussions with program faculty and students in the course and review recorded lectures asynchronously.

As the program continued to expand, additional course topics were added to the didactic curriculum to reflect emerging science, changes in the field, and feedback collected through summative surveys. By 2014, the program transitioned to a 16-week didactic course by including lectures on drugs of abuse, rodent models, sleep comorbidities with app development, and stress-related cognitive issues in PWH. By 2019, the program not only increased the number of faculty and topics due to demand, but the program also expanded even further by reaching trainees from over 30 universities, not only from across the United States, but beyond the US borders to Africa, Asia, Latin America, and Australia.

Component II. Mentored research scholar experiences and training

A second key goal for the TRNAMH training program was to attract highly qualified, innovative early-career scientists and encourage retention of these researchers in the field of neuroHIV by forging long-lasting connections between trainees and established professionals conducting research in the field. To encourage this, the program had a mentored Research Scholar Initiative. Trainees worked with their home and chosen Johns Hopkins faculty mentor (s) to develop a short (up to 3-month) research project, shadow experience or collect data. The trainee aimed to generate pilot data for future collaborations and grant applications and grow their professional research network in the neuroHIV field. To facilitate a structured and methodical plan for this project, trainees completed a series of guided questions with their TRNAMH mentors, to determine the scope of their project, scientific hypotheses, and specific aims for their progress, including short- and long-term goals for their participation. This aspect of the program was greatly under-utilized despite program coverage of travel and housing costs. Feedback from course participants suggests that it was difficult for many early career trainees to be away from their home institutions due to family obligations and other restrictions, both financial and logistical.

Component III. Competitive pilot grant funds

Pilot grant funding is pivotal and central to the advancement of early-career investigators as independent researchers, particularly for those who identify as underrepresented racial and gender minorities [51, 52]. Trainees who had taken the didactic course were eligible to apply for a one-year pilot grant in the amount of $20,000 awarded annually on a competitive basis. At the end of the didactic course, the pilot award announcement was sent to all course attendees inviting them to submit a competitive pilot award application.

Pilot award application and selection process

To simulate the competitive NIH grant submission process and prepare them for future grant applications, trainees competing for a pilot award were required to submit a 6-page R21 style grant, which included specific aims, a research strategy, pilot data (if available), budget, and biosketches of the principal investigator and other key personnel, as required by the NIH. Highly qualified trainees in the United States who had taken the didactic course were eligible to apply for a $20,000 grant to fund their innovative research projects. Pilot applications were reviewed and scored by the TRNAMH’s Review Committee, which included the Program Director, Co-Director, and the Executive Committee. Each member reviewed and scored the applications on a scale of 1–10 (1–2: outstanding; 2–3: excellent; 3–4: very good; 4–5: good; 5–6: acceptable; >6: unacceptable). Criteria for evaluation included innovation, experimental approach, mentoring plan, and expected outcomes. Selected applications were also reviewed by the designated NIH Program Officer for approval of funding before experiments could begin.

In the first year of the pilot grant program, TRNAMH awarded 4 trainees with research funding and has since awarded a total of 37 pilot grants between 2007 and 2019. Table 4, located in the Appendix, provides a full list of the innovative pilot grants by funding year and project title. Seventeen (17) pilot awardees out of 37 (49 %) subsequently received NIH grant funding. In the first iteration of the grant, the majority of candidates for the pilot grant program were identified as an underrepresented minority (URMs) in the sciences (Black/African American, Hispanic, Native American, Native Hawaiian/Pacific Islander). Out of the total pilot awardees, 26 (70 %) were women.

Due to the program’s very popular pilot grant initiative, renewal eligibility was expanded beyond URMs while maintaining a requirement that the research aligns with the program’s focus on neuroHIV and/or racial disparities affecting biomedical outcomes of the comorbid condition. Successful grant awardees have advanced the goals of this program, with 86 % (32/37) continuing independent research in neuroHIV and associated comorbidities, or mental health-related research (Table 3). The 14 % of awardees who did not continue in academic research are active in clinical, industry, or government-related careers. Of the pilot awardees who are continuing in independent research careers, at the time of surveying in 2021–2022, 84 % are now at the early-career level (Academia, Industry, Government), 8 % are postdoctoral, and 8 % are at the predoctoral level (Figure 3, Table 4).

Table 3:

TRNAMH pilot grant awardee characteristics and outcomes by race. Racial identity was determined via self-report.

	Total	Black	Hispanic	Pacific Islander	Asian	White
Number of pilot awardees	37	9	8	3	6	11
Number of women	26	8	4	3	2	9
Pre-TRNAMH career level
Pre-doctoral	10	3	1	1	1	4
Post-doctoral	15	3	2	1	4	5
Early career	12	3	5	1	1	2
Post-TRNAMH career level
Pre-doctoral	3	1	0	0	0	2
Post-doctoral	3	0	0	1	0	2
Early career	31	8	8	2	6	7
Post-TRNAMH career and funding
Academia	28	4	6	3	5	10
Clinical	3	3	0	0	0	0
Industry	5	1	2	0	1	1
Government	1	1	0	0	0	0
Ongoing NeuroHIV research	32	5	8	3	6	10
NIH grants funded	26	5	3	2	9	7
Publications
Total	1066	354	138	38	195	341
Total post-pilot award	721	242	103	36	98	242
First author	167	55	22	7	19	64
Middle author	444	133	68	29	73	141
Last author	110	54	13	0	6	37

Figure 3:

Comparison of career levels before and after receiving a TRNAMH pilot grant.

Table 4:

Award years and project titles of Innovative pilot awards funded by the TRNAMH Program from 2007 to 2019. The most recent projects were completed by 2021.

Award year	Pilot awardee	Project title
2019–2021	Sanjay Kumar, PhD, MS	“HIV-1 entry into neuronal/glial cells and the underlying mechanism(s) of exosome-dynamics in cocaine abuse”
2019–2021	Palsamy Periyasamy, PhD (+)	“HIV Tat-mediated astrocyte activation involves NLRP6-mediated pyroptosis: implications for neuroinflammation in HAND”
2019–2021	Susmita Sil, PhD (+)	“Molecular mechanisms involved in Alzheimer’s like comorbidity of HAND”
2019–2020	Claire Lyons, DVM	“Effect of social stress on dopaminergic and serotonergic pathways in the CNS of SIV infected macaques”
2019–2020	Danielle Clements PhD	“Investigation of co-receptor usage in a myanmar pediatric HIV cohort using next generating sequencing and implications for neurocognitive outcomes”
2018–2019	Audrey Knight, PhD	Dysregulation of central nervous system glial immune responses in a cART—suppressed SIV/macaque model of chronic HIV CNS disease
2018–2019	Bethany A. Reinecke, PhD	Bivalent Ligand approach to explore MOR-CXCR4 crosstalk in opioid enhanced NeuroAIDS
2018–2019	Ashutosh Tripathi, PhD	Combinatorial effects of HIV & cART in mediating microglial activation via dysregulated autophagy: Implications for neuroinflammation underlying HAND
2018–2019	Bianca Cotto, PhD	Combined effects of HIV-1 Tat and cocaine on astrocyte metabolic functions and the impact on to rapid aging in the CNS
2017–2018	Mario Bianchet, PhD (+)	Regulation of HIV-1 Tat proteostasis as a latency switch and neuroprotective strategy
2017–2018	Kristen Hollinger, PhD	Neutral sphingomyelinase 2 inhibition for the treatment of HIV-associated neurocognitive disorders
2017–2018	Crystal Leibrand, PharmD, PhD	Structural and functional consequences of HIV-1 viral proteins and morphine exposure at the blood-brain barrier
2017–2018	Xiaolei Zhu, MD, PhD (+)	Treating HIV-associated neurocognitive disorder (HAND) using a traditional Chinese medicine ingredient: repairing gut microbiota dysbiosis-induced sustained inflammation via inhibition of nonTLR-mediated inflammatory signaling
2016–2017	Dionna Williams, PhD (+)	“Antiretroviral therapy efficacy in the central nervous system”
2016–2017	Minglei Guo, PhD (+)	“Studies related to the effects of drugs of abuse and/or HIV on CNS dysfunction”
2013–2014	Raissa Menendez-Delmestre, PhD	Interplay of HIV-associated neurocognitive disorders with obesity
2013–2014	Kimberly Smith, MD	A streamlined assessment program to promote engagement in care for traditionally marginalized populations following an HIV diagnosis
2013–2014	Yoelvis Garcia Mesa, PhD	Ligand-activated nuclear receptors regulate HIV latency in microglial cells
2012–2013	Bryan Smith, MD (+)	The effects of aerobic exercise on cognitive performance for individuals with HIV-associated cognitive disorder
2012–2013	April D. Thames, PhD (+)	Proinflammatory genotypes and susceptibility to HIV-associated neurocognitive disorder in african-americans
2012–2013	Rosa J. Rodriguez PhD, MPH, MS	Validation and use of the spatial navigation memory island test in evaluation of HIV-associated cognitive disorder
2012–2013	Sarah E. Beck, MD (+)	Immune selection of SIV in the CNS: costs and consequences
2012–2013	David Alvarez-Carbonell, PhD, MBA	The fractalkine and ErbB receptors as regulators of HIV latency in infected microglia cells: implications for HIV-associated neurocognitive disorders
2012–2013	Yamil Gerena, PhD (+)	Soluble insulin receptor, lipidomic dysregulation, and insulin resistance in HIV+ women with HAND
2012–2013	Jennifer Lyons, MD	Remote assessment of HAND in cape coast, Ghana: a Pilot study
2011–2012	Kelly Metcalf Pate, DVM, PhD (+)	The role of thrombopoietin in the pathogenesis of SIV-associated CNS disease
2010–2011	Nicholas Kenney, MD (+)	Detection of Cripto-1 in murine cortical brain tissue
2011–2012	Crystal Bethel-Brown, PhD, MBA	HIV-1 Tat and alcohol-mediated disruption of brain endothelium: role of platelet-derived growth factor-BB (PDGF-BB)
2011–2012	Valeria Avdoshina, MD, PhD (+)	Contribution of TrkB promoter mutation to HIV-associated depression
2009–2011	Valerie Toodle, PhD	Neuroprotective and neurorestorative effects of fluconazole against HIV proteins and mitochondrial toxins
2009–2011	Marilou Andres, PhD (+)	APOE expression in the CSF of patients with HIV-1 infection
2009–2011	Crystal Watkins, MD, PhD	Imaging immune mechanisms of depression in older HIV patients
2009–2011	Jose W. Rodriguez, MD (+)	Neuroprotective effect of tobacco cembranoid: Therapeutic implications for HIV-associated neurocognitive disorders
2008–2010	Summer Acevedo, PhD	Association between 14-3-3e, cytokines, and HIV-associated neurocognitive disorders in women
2008–2010	Charlene Gamaldo, MD	The relationship between HIV-associated neuropathy and insomnia
2008–2010	Juliana Perez-Laspuir, PhD (+)	Neuroprotective candidates for HIV-associated neurocognitive disorders
2008–2009	Melissa Agsalda, PhD (+)	HIV DNA in CNS compartments about HIV-associated neurocognitive disorders

1. (+) Indicates pilot awardee received subsequent NIH grant funding since receiving the TRNAMH pilot award.

Mentorship and collaboration

Providing a strong foundation in the pathophysiology of HIV, its complications in PWH, and the development of treatment strategies, coupled with mentored research and funding mechanisms for new and early-stage investigators were essential components of the model for our program. Especially important for trainees from underrepresented backgrounds is a program where they can be directly mentored and provided with opportunities for career and scientific development. TRNAMH’s network of neuroHIV experts provided the participants with an opportunity to meet, discuss, and build collaborations that may otherwise not have been made without this type of training program. Those who participated in the Research Scholar component were given even more opportunities through hands-on, in-person research experiences. An additional activity of the program in the beginning years included a networking dinner at the Society for Neuroscience conference to facilitate connections between trainees and program faculty. The overall logic diagram of the resources, qualifications, methodology, and desired outcomes of the program is exhibited in Figure 4.

Figure 4:

Logic diagram for TRNAMH program. Illustrates the resources, goals, and criteria for program participation, and intended outcomes for course participants.

Ongoing considerations for the TRNAMH course: lessons learned

In the rapidly evolving disciplines of neuroHIV, the TRNAMH program has been successful in supporting highly qualified early-career students and scientists from underrepresented minorities, a key factor in improving the effectiveness and innovation of research in this field. As previously discussed, with a disease like HIV infection that disproportionately affects non-white communities worldwide, having a more diverse cohort of neuroHIV researchers would be a monumental step towards more equitable, valid, and generalizable research [39]. Previous reports showed that the lack of diversity in the biomedical workforce relative to the general population may be a key factor that continues to contribute to health disparities and inequalities [53]. The goal of reducing these racial and ethnic disparities in our trainee pool and subsequently retaining them in the neuroHIV field were key features of the TRNAMH program.

Diversity and inclusion initiatives began in earnest within biomedical research training programs; however, translating the outcomes of these programs into demonstrable changes in the makeup of the research workforce remains a challenge. While some improvements were seen at the graduate student level (over the past 10 years, there have been reported increases in the proportion of female, underrepresented minorities, and/or disabled graduate applicants, students, and post-docs [41, 42]), the overall diversity of junior and senior faculty, professors, and major grant awardees has not changed commensurately. This represents a multi-layered barrier at the early-career level for these diverse students to succeed, a combination of inadequate opportunities for continued research support, high-level training, or other interpersonal factors that lead these individuals to leave the biomedical workforce or academic tenure track. Training programs like TRNAMH seek to resolve these barriers, providing additional opportunities that these trainees may not otherwise be given, to overcome institutional (structural racism, unconscious bias) and historical gaps (inequity, geography) that often limit professional progress.

The success of the TRNAMH program was also evident from feedback received from the trainees. The trainees reported significant value in the experience and a high likelihood of recommending this program to colleagues within neuroHIV research. In particular, the trainees who were awarded pilot grant funding have gone on to be successful, innovative researchers in their fields even at an early career stage, with the majority continuing to do neuroHIV research to this day. TRNAMH made headway in addressing several barriers that were identified as potential reasons for the lag in more minority representation in the biomedical research fields by providing a scientific network, hands-on research experiences, and pilot grant funding, which also provided tailored mentorship. In line with our program’s goal to develop a neuroHIV research workforce from the ground up that is more representative of the racial diversity of the general population, our outcome data thus far shows a promisingly diverse enrollment in the TRNAMH course (Figure 2a), as well as the majority of our trainees entering the program (72 %) at the predoctoral or postdoctoral level (Figure 2b). This small investment in the continued engagement of the trainees can have long-lasting and tangible benefits.

Capitalizing on the web-based format of the program played a significant role in expanding our reach to institutions, faculty, and trainees worldwide. Virtual technology improvements allowed for the program to continue despite trainees learning at a distance, from their home institutions. However, feedback from both trainees and faculty mentors acknowledged some challenges to participation in this program without face-to-face involvement. The improvements in our virtual platforms over the years, as well as the opportunities for on-site research training for students in the program, and pilot grant funding, helped to offset institutional infrastructure limitations that are encountered at their institutions, also providing access to techniques and methodology that might not have been available except with collaborations fostered by Johns Hopkins and our extensive collaborative network of investigators. Adopting technology early in the process to enhance communication across the continent and across time zones is another key feature and foresight of the developers of this course that contributed to its success.

Though the improvements in online platforms used by TRANMH have mostly benefitted and streamlined access, communication, and interaction for the trainees, virtual participation in the TRNAMH program did face some difficulty accommodating trainees who had other academic obligations at their home institutions. Scheduling time with mentors, lab meetings, and consistent check-ins, despite the time-zone differences were some of the unanticipated difficulties of not bringing all trainees locally to Baltimore, although we believe that we have made and will continue to make significant improvements in these areas over time. After our grant renewal in 2015, we altered the admissions criteria for the program, allowing non-URM trainees to participate in the course, provided that they were still conducting research in the neuroHIV field and/or addressing racial/ethnic disparities in the biomedical sciences. However, the subsequent decline in the proportion of URM trainees in these more recent years may reflect a need for a renewed effort to continue to recruit consistently higher proportions of these URM trainees who may also face the additional challenge of navigating post-graduate training amid the COVID-19 pandemic, which has been shown to disproportionately and negatively affect people and students of color [54–57]. Whether these challenges are financial, interpersonal, or logistical, remain to be seen, but addressing these additional barriers will certainly be an important focus as we continue to determine how best to ensure equitable access to high-quality biomedical neuroscience and HIV research training for the future years of our program.

TRNAMH’s yearly feedback surveys helped to determine whether participants felt that they had gotten value out of the course, and ways that the program could be improved. These surveys were extremely useful, providing insight into the motivations of our trainees, and confirming our hope that the course is achieving the set goals of the program for the trainees it is intended to serve. Boxs 1 & 2 provide a snapshot of trainee responses to survey questions related to personal value and ways to improve the program.

Addressing ongoing challenges to biomedical workforce diversity

In 2019, neuroHIV researcher Dr. David Stoff identified 4 major challenges to the goal of successfully diversifying the workforce of researchers in our field [39]: (1) inadequate understanding of the unique workforce dynamics that contribute to or detract from feelings of belonging for URMs [58, 59]; (2) poor retention of URM trainees and scientists or “leaky” professional advancement pipelines that discourage these individuals from progressing [45, 46, 60]; (3) inefficient integration of R25 funding mechanisms into the infrastructure of academic research departments to support trainees [61, 62], and (4) qualities of the institution’s mentor climate that do not sufficiently support the needs of the URM trainees [63–65]. Our program has made significant progress addressing these points, focusing on training the cohort to understand the impact of their work in the context of racial and ethnic disparities that exist not only in the incidence and impact of HIV but the workforce that studies it; offering additional funding and mentorship to overcome pipeline leaks that may have otherwise led some of these professionals to leave the field; and allowing our URM trainees the opportunity to learn from and be mentored by faculty professionals who are also themselves, URMs. Though the R25 funding that supported this program has not yet overcome Dr. Stoff’s challenge 3, we believe the other successes are evidence that more progress is not just feasible, but necessary. In particular, the pilot funding that our program was able to provide was significant: as indicated in Box 2, at least one of our cohort members confirmed that additional funding, by raising the pilot grant award from $20–50 K, would have been even more impactful. Prior studies showed that early career stage funding plays a key role in fostering successful scientific careers, particularly in members of these URM groups, which in turn is likely to contribute to overcoming many of the barriers that remain for successful initiatives for diverse academic faculty [51, 52]. With the addition of enhanced mentored training, which we provided in our TRNAMH program, career development progress for URM scientists in these fields is also expected to accelerate [66].

In conclusion, the Translational Research in NeuroHIV and Mental Health program achieved 12 years of outstanding progress toward improving the breadth, depth, and diversity of the researchers engaged in neuroHIV research. The development of this program addressed key areas of improvement in this branch of the biomedical sciences. The unique aspects of this program as discussed above represent a model for others to follow. All the same, we intend to continue addressing the feedback received over the last 12 years from our participants, institutions, and trainees to continue to enrich mentorship opportunities, expand the curriculum, and fund highly innovative research geared towards minimizing disparities and improving access to opportunities and resources towards a better understanding of neuroHIV.