SUMMARY Increased attention must be given to the health of women living with HIV (WLHIV) across all stages of their lives, especially in sub-Saharan Africa and countries like Kenya where girls and women have the highest HIV prevalence and rates of new infections. Emphasis on women’s health is critical because WLHIV face unique health challenges and are often disproportionately affected by co-morbidities, especially as they age. It is essential that institutions build the in- country capacity to design and conduct research that will improve health of WLHIV. This is the primary goal of the parent D43 Fogarty-funded program, led by Drs. Elizabeth Bukusi (Kenya Medical Research Institute [KEMRI]) and Carey Farquhar (University of Washington [UW]), is entitled Women and HIV: Translation of Research into Practice (WHIV). In this application, we propose to complement what we are doing in the parent award and provide funding, mentorship and support for recent graduates of the D43 program who are on the path to becoming independent investigators. From 2015 to the present, our WHIV Fogarty training program has supported 27 researchers as they earned advanced degrees at the UW and University of Nairobi (23 MPH, 4 PhD). We have found that post-graduate funding is essential to ensure the success of our recent graduates as they transition to initiating independent research on HIV and women’s health. For this supplement we solicited concept notes from all eligible trainees and identified 4 MPH graduates to compete with full proposals for two fellowship positions. Our Training Advisory Committee will select the two awardees who will receive stipend and research support for their studies. They will also receive high-quality mentorship from experienced teams of KEMRI and UW mentors and participate in online research seminars, manuscript and grant writing workshops, and regular meetings with the MPIs, their peers and their mentors to review their research progress and discuss important career development topics. The WHIV D43 has used this approach with post-doctoral fellows to fill funding and mentorship gaps after graduation and will build on that successful experience.

1. Background The burden of HIV disease worldwide remains disproportionally concentrated in sub-Saharan Africa (SSA), the only region with the majority of HIV infections occurring among women and a region with exceptionally high rates among young women aged 15-24. Control of the HIV epidemic globally, in SSA and in a country like Kenya in the top 10 high HIV burden countries requires increased attention to the condition of women and adolescent girls. In such countries effective implementation and expansion of HIV prevention and treatment interventions that have been proven to work are urgently needed. In addition, it is critical to understand the biological, psychological and structural factors, as well as unique co-morbidities, that women living with HIV (WLHIV) face, especially as they age. Building the in-country capacity to design and conduct implementation-focused research addressing the health of women affected by HIV is the primary goal of the parent Fogarty-funded program led by Drs. Elizabeth Bukusi (Kenya Medical Research Institute [KEMRI]) and Carey Farquhar (University of Washington [UW]), entitled, Women and HIV: Translation of Research into Practice (WHIV). From 2015 to the present, the WHIV Fogarty training program has supported 27 researchers as they have earned advanced degrees at the University of Washington and University of Nairobi (23 MPH, 4 PhD). One major challenge for these trainees has been bridging the gap between their advanced degree training and establishing an independent research career. Those who have successfully obtained a K43 or similar career development award have been able to launch their research careers. Those who have not been able to secure post-graduate funding have had a more challenging time achieving independence and instead have largely remained as co-investigators on others’ grants. Post-graduate funding is essential to ensure success of recent graduates conducting research to address important gaps in the health of women living with HIV and increase our understanding of the intersectionality of HIV infection and women’s health, and the long-term effects of HIV for women. Providing funding, mentorship and support for new investigators to successfully transition into initiating independent research on HIV and women’s health issues is the primary goal of this supplement. 2. Objective We propose to leverage the KEMRI/UW WHIV Fogarty D43 training program to increase capacity for research responsive to this request for applications by supporting two new investigators who recently graduated with an MPH from UW. They will conduct high-impact mentored research in Kenya focused on health of WLHIV across the lifecycle, leading to their independence as an investigator and a strong foundation for a research career. 3. Approach 3.1 Overview The supplement will support two new MPH graduates launch their research careers in Kenya by providing by providing them with tools, mentorship, and experience to bridge them to an independent career in HIV research focused on women living with HIV and women’s health at KEMRI and partner institutions. The one-year post- graduate fellowship award includes funding for a stipend and for the candidate’s own research project. It also includes mentorship from a team of highly qualified KEMRI and UW researchers, individual coaching, group meetings, seminars, and skills- building workshops to promote their career development. 3.2 Program leadership The proposed program will be directed by Dr. Elizabeth Bukusi at KEMRI with support from Dr. Carey Farquhar and the administrative team at UW. Both Drs. Farquhar and Bukusi have substantial experience with Fogarty training programs, as well as other training programs in Kenya. They have been successfully co-directing the Women and HIV: Translation of Research into Policy training program since it was funded 9 years ago and are excited to continue to work together and co-lead activities proposed in this supplement. Elizabeth Bukusi, MBChB, MMed, MPH, PhD, Program Director, is an obstetrician/gynecologist, epidemiologist and a Chief Research Officer at the Center for Microbiology Research, KEMRI. She earned an MPH in 2000 and PhD in Epidemiology at the UW in 2006. Dr. Bukusi was awarded a postgraduate diploma in research ethics (University of Cape Town) in 2010 and completed a master’s degree in Bioethics. Her research focuses on sexually transmitted infections, reproductive health and HIV prevention, care and treatment and she was one of the two co-founders of KEMRI’s Research Care and Treatment Program (RCTP). She was founding chair of KEMRI’s Program on Sexual, Reproductive, Adolescent and Child Health and currently serves as Core Faculty for the Fogarty-funded UCSF Glo-Cal Fellowship. She co-chaired the HPTN Women at Risk Committee and serves on the Kenya MOH National HIV Prevention Task Force. In the last 25 years she has mentored over 100 Kenyan and international scholars and is the PI/Co Director for a FIC Bioethics Training Program expanding Masters training in 2 Kenyan universities. She is also an accredited executive coach. Carey Farquhar, MD, MPH, Program Director, is a Professor jointly appointed in the Departments of Global Health, Medicine and Epidemiology at the University of Washington and Director of the UW IARTP since 2003. In May 2022, she was appointed the Interim Chair of the UW Department of Global Health. Her research has focused most recently on HIV testing and assisted partner notification services in Kenya, HIV and cardiovascular disease risk factors, and research with marginalized and unreached populations, such as persons who inject drugs. She has mentored more than 60 US and Kenyan trainees earning degrees at UW and published more than 260 papers on HIV-related topics, global health leadership and capacity building in under-resourced settings, ~25% of which have her trainees as first author. Several of her trainees have been successful obtaining NIH career development awards, such as the GRIP (1), K43 (3), K01 (1), K23 (2), as well as NIH Diversity supplements (2). 3.3 Selection process The KEMRI/UW WHIV program has issued a request for proposals from our alumni and networks and has identified 4 post-graduate researchers as finalists for this funding opportunity. These 4 will submit full-length proposals for review by the WHIV Technical Advisory Committee (TAC) which will recommend two finalists to receive research funding and support for the one-year fellowship. TAC members include Dr. Dorothy Mbori-Ngacha, Dr. Criag Cohen, Dr. Patty Garcia, Dr. Edwin Were and Dr. Joseph Zunt. All 5 have extensive experience with Fogarty training programs and have been WHIV TAC members since 2015. They are familiar with the training opportunities, mentors, and resources available in Kenya for graduates of the WHIV program and will be able to identify trainees with the highest potential for success, the strongest mentorship teams, as well as those projects that are high-impact and feasible in the available timeframe available. They will be provided with a rubric and asked to assess the applications using criteria for the candidate, proposed mentorship team and the research project. Candidates must have a track record of excellent performance and a clear goal statement, expressing their commitment to working in the field of women’s health and HIV; mentorship teams must include mentors at both KEMRI and UW who have expertise in the research area as well as in mentoring trainees at this level; research projects will be considered based on their responsiveness to the call for research on women living with HIV across the lifecycle and their potential for impact, innovation and feasibility. 3.4 Finalist candidates and proposed studies The 4 finalists for this post-graduate fellowship are listed below followed by brief biographies and overviews of the research projects they are proposing and their mentorship teams (Table 1). Biosketches for the finalists are also included as attachments to this proposal. Of these 4 finalists, 2 will be selected by the WHIV TAC for the post-graduate fellowship which will include funding project expenses, as well as a stipend to provide fellows with time to conduct the research. Shradha Doshi, MBChB, MMed, MPH: Cardiovascular health and risk stratification in women aging with HIV Dr. Shradha Doshi is a medical doctor from Kenya. She earned her Bachelor of Medicine, Bachelor of Surgery, and Master of Medicine degrees from the University of Nairobi, Kenya. She has 16 years of experience as a doctor, nine of which she has focused on HIV care and treatment. As a consultant physician, Dr. Doshi practices clinical medicine at The Aga Khan University Hospital in Nairobi, Kenya. She has also worked in HIV prevention research in Kenya with the Kenya Medical Research Institute. Her primary research interests were pulmonary hypertension and the use of cardiovascular biomarkers as diagnostic, prognostic, and predictive markers in heart failure. Dr. Doshi received her MPH in Global Health from the UW in 2023 and her thesis was entitled, “Association between mild chronic kidney disease and coronary artery disease in persons living with and without HIV in Uganda.” Dr. Doshi proposes to conduct a cross-sectional study involving 100 women over the age of 50 who are living with HIV. This study aims to evaluate cardiac abnormalities in older women living with HIV by utilizing 2D echocardiograms and NT-pro BNP levels and factors associated with this finding. Few studies have assessed comprehensive aging data with echocardiographic assessments and biomarker analysis. Dr. Doshi aims to fill the gap by enhancing understanding of the interplay between frailty, osteoporosis, and cardiovascular health in this population. The specific aims include 1) to determine the prevalence of cardiac abnormalities in older women living with HIV using 2D echocardiographic assessments. 2) To evaluate the levels of NT-pro BNP as a biomarker for cardiovascular risk and potential heart failure in older women living with HIV. 3) To correlate traditional cardiovascular risk factors and NT pro-BNP levels with echocardiographic findings. The study will leverage the supplement to the Fogarty-funded D43 award entitled, Women and HIV: Translation of Research into Policy (TW009783). The parent study investigates the prevalence and correlates of frailty and osteoporosis among women aged 50 and above with HIV. Dr. Doshi will utilize existing data from the parent study, including age, sex, duration of HIV, antiretroviral therapy (ART) usage and type, CD4 count and viral load, history of cardiovascular risk factors like smoking, diabetes, hypertension and body mass index (BMI), current HbA1c levels, and dual-energy X-ray absorptiometry (DEXA) scan parameters such as T-score and body composition and frailty scores. The study will additionally conduct blood draws to measure NT-pro BNP levels to screen for potential heart failure. She will also collect additional data on structural and functional cardiac status by performing 2D Echocardiography and NT pro-BNP on participants. Table 1. WHIV Post-graduate Fellow Candidates, Proposed Research and Mentors Name/Title Date, Degree, Institution Research Area Mentors Shradha Doshi, MBChB, MMed, MPH August 2023, MPH in Global Health, University of Washington Cardiovascular health and risk stratification in women aging with HIV Sarah Masyuko, Carey Farquhar, Chris Longenecker, Elizabeth Bukusi, Rose Bosire Stanley Ndwiga, MBChB, MPH June 2024, MPH in Global Health, University of Washington Psychosocial factors influencing viral suppression among adolescents and young adults living with HIV Kenneth Ngure, Nelly Mugo, and Kenneth Mugwanya Marilyn Nyabuti, MBChB, MPH August 2024, MPH in Global Health, University of Washington Structured counseling and warm handoffs to promote successful linkage of WLHIV during the transition from maternal and child health clinics to comprehensive care centers Carey Farquhar, James Ayieko, and Cyrus Mugo Dismas Ouma, MBChB, MPH June 2024, MPH in Global Health, University of Washington Evaluating the integration of point of care for STI screening into the routine care of women living with HIV aged 18-49 years Susan Graham,. Elizabeth Harrington, Cyrus Mugo, Maricianah Onono, and Elizabeth Bukusi Stanley Ndwiga, MBChB, MPH: Exploring the Psychosocial Factors Influencing Viral Suppression among Adolescents and Young Adults Living with HIV: A Qualitative Follow-up Study Dr. Stanley Ndwiga is a medical doctor at the Kenya Medical Research Institute (KEMRI) and most recently was a study coordinator, supervising teams of research clinicians. He also coordinated study regulatory matters, drafted SOPs and trained study staff on study protocol and study operational manuals. For the last three years, he has worked in HIV prevention research in Kenya with KEMRI. Dr. Ndwiga received his MPH in Global Health from the University of Washington in June 2024. Dr. Ndwiga’s study aims to provide deeper insights into the psychosocial challenges faced by Adolescents and Young Adults (AYA) living with HIV to inform the development of targeted interventions and improve adherence to ART and viral suppression. The findings will help healthcare providers tailor support services to better meet the needs of this population and contribute to the broader literature on HIV care and support, particularly in Kenya and similar resource-limited settings, highlighting the importance of addressing mental health, stigma, and social support in the management of HIV among AYA. The primary objective of this study is to explore the personal experiences and perspectives of adolescents and young adults living with HIV, focusing on how psychosocial factors affect their ability to achieve and maintain viral suppression. The secondary objectives include identifying barriers and facilitators to achieving viral suppression, understanding the role of primary care givers and other social support systems and stigma in adherence to antiretroviral therapy (ART), and exploring the coping mechanisms and interventions that AYA find most acceptable and effective. This study will employ a phenomenological qualitative design, utilizing in-depth interviews and focus group discussions to gather detailed information. The population of interest includes AYA aged 15-24 years living with HIV who participated in a previous quantitative study. The study will be conducted at the Thika Partners in Health Research and Development (PHRD) research clinic in Kiambu County, Kenya, and will also include participants from Murang’a and Nairobi Counties. Purposive sampling will be used to select participants who exhibit a range of experiences with viral suppression and psychosocial challenges. Data will be collected through the use semi-structured interview guides informed by the CFIR framework and conducted by trained qualitative researchers. Thematic analysis will be used to identify and interpret patterns and themes related to psychosocial factors and their impact on viral suppression. Marilyn Nyabuti, MBChB, MPH: Structured counseling and warm handover to promote successful linkage of WLHIV during the transition from MCH to CCC Dr. Marilyn Nyabuti is a medical doctor trained at the University of Nairobi, Kenya, and is a team lead/co- investigator in a NIH-funded clinical trial in Western Kenya. She received her MPH in Global Health from the University of Washington in August 2024. Dr. Nyabuti’s research interest lies in understanding the unique cyclic barriers adolescents and youth seeking HIV prevention and treatment contend with as they transition through the different life-stages. Dr. Nyabuti’s study aims to provide evidence demonstrating the need for guidelines to assist healthcare providers to ensure uniform services for women living with HIV during the transition period from MCH to CCC, and to reduce the incidence of treatment interruptions among these women. Dr. Nyabuti proposes an intervention to provide targeted psychosocial counseling three months in advance, followed by a warm handover to CCC staff for WLHIV at increased risk of HIV treatment interruption (women <25 years, screening positive for depression, and newly diagnosed with HIV during PMTCT follow-up). The specific aims of this intervention are: 1) To evaluate the correlation between structured psychosocial counselling and warm handover and successful linkage to CCC during transition from MCH to CCC. 2) To assess the impact of counselling and a warm handover during transition from MCH to CCC on one year retention in HIV care. 3) to estimate the incremental cost of offering targeted counselling and a warm handover to WLHIV during the transition from MCH to CCC. Dr. Nyabuti will use a cluster-randomized control study with randomization at clinic level to enroll at least 300 women living with HIV aged 15 years and above who have completed PMTCT follow up and are scheduled for transition to the CCC who screen positive for any form of depression or aged <25 years old or newly diagnosed with HIV during PMTCT follow up. Each participant will have 4 study visits as follows: 3 months prior to transition, on day of transition, within 2 weeks after CCC appointment date, and 1 year post transition. Additionally, she will collect micro-costing and time and motion data to compare the resources used to deliver the intervention to the resources used in standard of care. She postulates that the intervention will reduce the proportion of women who miss their initial visit at CCC after transition and facilitate sustained retention up to 1 year post transition thus improving their health outcomes and improving their quality of life. In addition, she hopes that her results will inform the development of clinical guidelines that will guide healthcare workers when transitioning women from PMTCT to CCC. Dismas Ouma Congo, MBChB, MPH: A pilot study to evaluate the integration of point of care for sexually transmitted infection screening into the routine care of women living with HIV aged 18 to 49 years Dr. Dismas Ouma Congo is a research scientist at the Kenya Medical Research Institute (KEMRI), Centre for Microbiology Research in Kisumu. In this role, he develops clinical standard operating procedures, executes them, ensures participant safety and general health, and submits safety reports to both sponsors and local ethics committees. Dr. Ouma Congo received his MPH in Global Health at the University of Washington in June 2024 and was awarded the Outstanding MPH Student award by the Department of Global Health. Dr. Ouma proposes a study to evaluate organizational readiness, as well as the feasibility and acceptability of the use of POCT for STI screening and management, using self-collected genital swabs in the Lumumba subcounty HIV care clinic in Kisumu County. His proposed study hinges on the central hypothesis that a POCT for STI testing that integrates self-collection by WLHIV and links them to treatment offers distinct advantages from a syndromic or provider-collected swab approach. According to UNAIDS 2022 report, approximately one million women aged between 15-49 years were living with HIV in Kenya, with the highest incidence of new HIV infections occurring among women aged 15-24 years. No studies in Kenya currently assess the use of POCT for STI testing among WLWH, the most affected group, and allowing for self-collection of samples. This study includes the following aims: 1) To determine factors influencing the acceptability and feasibility of POC STI testing for WLHIV, and characterize baseline readiness to implement POC STI testing. The study will administer surveys and conduct workshops with WLWH attending their routine care clinic and the healthcare providers to assess the acceptability and feasibility of POC STI testing. 2) To pilot POC STI testing for WLWH and determine early implementation outcomes, including acceptability, feasibility, appropriateness, and understand factors necessary for expanded use. The study will pilot the use of POC STI testing among 100 WLWH-attending their routine HIV care clinic using self-collected swabs. Dr. Ouma will use the laboratory at the Lumumba CIS building to conduct POC STI testing for CT, GC, and TV. This laboratory has staff with extensive experience in POCT for STIs. The estimated turnaround time is 2 hours. Those who test positive will be treated according to 2022 National STI treatment guidelines and offer intimate partner notification and testing for those who agree to notify their sexual partners. Dr. Ouma will also administer surveys to assess factors associated with STIs including socio-demographic variables, sex and relationships, and reproductive history. He will also conduct a focus group discussion with WLWH and key informant interviews with providers to assess factors necessary for expanded use of POC STI testing in HIV clinics using self-collected swabs. Responsible Conduct of Research (RCR): All the trainees identified as finalists for this fellowship have completed the RCR course at the University of Washington in Fall 2022 and have met NIH’s RCR training requirements. 3.5 Mentors Mentorship will be a critical component of this project. The post-graduate fellows will meet weekly with mentors and the entire team (fellows and mentors) will meet quarterly to report on professional development goals and research updates. The trainees will also participate in monthly IARTP seminars and other forums. In addition to the program leaders, the mentorship team at KEMRI and UW includes: Sarah Masyuko, MBChB, MPH, PhD, Assistant Professor, UW Department of Global Health. Dr. Sarah Masyuko received her Masters in Global Health and her PhD in Global Health-Implementation Science from the University of Washington. She has been the lead of the HIV Testing Services and Pre Exposure Prophylaxis (PrEP) program at the National AIDS and STI Control Program (NASCOP) with the Kenyan Ministry of Health. Dr. Masyuko has been involved in research that spans from designing, implementing, disseminating and bringing to scale evidence-based health interventions. Her research interests are in implementation science with the direct translation of research results into policy and practice in HIV Prevention, Care and Treatment and Non- communicable diseases in low- and middle-income countries. Cyrus Mugo, MBChB, MPH, PhD, Senior Research Scientist at Kenyatta National Hospital. Dr. Mugo received his Masters in Global Health and his PhD in Epidemiology from the University of Washington. His research focus has been on improving treatment outcomes for adolescents and young adults living with HIV. He has 10-years of experience coordinating pediatric and adolescent HIV research across the care continuum, which includes multiple clinical trials and implementation science projects in Kenya. Dr. Mugo has been the PI of two studies, one, looking to strengthen the viral load monitoring for children and adolescents by identifying gaps in the monitoring cascade and their solutions using failure mode and effect analysis, and two, a longitudinal study on patterns and effect of self-disclosure of HIV status by adolescents and young adults living with HIV. Nelly Rwamba Mugo, MBCH, MMED (Ob,Gyn), MPH: Senior Principal Clinical Research Scientist KEMRI Dr. Mugo is a reproductive health specialist with three decades of work experience. Her research focus has been on prevention of HIV and cervical cancer among other reproductive health research work. She has been an investigator on two landmark clinical trials, the Partners PrEP study that contributed evidence to inform the change of indication for use of Truvada as HIV prevention pre-exposure prophylaxis (PrEP), and a protocol lead for the on-going ‘Kenya Single-dose HPV Vaccine-Efficacy (KEN SHE) Study –’ that has provided evidence on efficacy of single dose HPV vaccination. Dr. Mugo is a member of the International Papillomavirus Society education committee, the Kenya Obstetrics and Gynecology society, and has contributed to several World Health Organization and Kenya ministry of health working group scientific committees. Chris Longenecker, MD. Dr. Longenecker is a non-invasive cardiologist and Associate Professor in the Division of Cardiology and Department of Global Health at the UW School of Medicine. He is the inaugural Director of the Global Cardiovascular Health Program, a joint initiative of cardiology and global health. Clinically, he attends on the Harborview cardiology consultative service and is director of a unique HIV-Cardiology clinic within the Madison Clinic at Harborview. Dr. Longenecker’s research, which is primarily in the USA and Uganda, focuses on mechanisms and prevention of cardiovascular disease in people living with HIV, with a secondary focus on quality of care and outcomes for people living with rheumatic heart disease. Kenneth Mugwanya MBChB, MS, PhD. Dr. Mugwanya is a physician-epidemiologist and an Assistant Professor in the Department of Global Health at the UW. His research focuses on multidisciplinary studies of epidemiology and prevention of HIV and other STIs, implementation science, and antiretroviral PrEP pharmacology in African populations, particularly among young women. Over the past decade, he has led or collaborated on pivotal HIV prevention studies involving >30,000 HIV at-risk participants that have advanced PrEP implementation and HIV prevention for populations in Africa and globally. 3.6 Career development support a. Research work in progress meetings: In addition to weekly meetings with individual mentors and monthly meetings with mentoring teams, all fellows and mentors will meet quarterly to report on professional development goals and share research progress. These will be facilitated by Drs. Bukusi and Farquhar. b. Leadership coaching: To enhance research leadership skills, mentees will have monthly scheduled leadership coaching sessions with Dr. Bukusi. These sessions will help clarify their career trajectory, build confidence in any areas identified for additional skills building and enable professional development of skills that are useful for successful career development, including but not be limited to improving self-awareness and clarification of leadership styles, work life balance, conflict management and negotiating. c. Grant and manuscript writing training: The fellowship with include grant writing and manuscript writing workshops. The grant writing workshops will be focused on development of K43 and other funding opportunities. The manuscript writing workshops will include a focus on publishing their MPH and fellowship research results. d. UW Kenya Research and Training Center (KRTC) seminars: The trainees will also participate in monthly KRTC seminars offered on Zoom on the third Tuesday of each month. The seminars are held at a time to prioritize Kenyan participation. Below is a list of selected KRTC seminars this last year: 1. Cardiovascular Health Research and Training in Kenya. UW Global Cardiovascular Health Program, April 18, 2023. 2. Optimizing COVID-19 Vaccine Uptake Among PLHIV. Nancy Ngumbau, Kenyatta National Hospital, June 30, 2023. 3. The Kenya Data Protection Act 2019 – What you Need to Know as a Researcher. Antony Kariri, University of Nairobi, February 27, 2024. 3.7 Timeline We have solicited full proposals from the 4 finalists. These will be submitted by July 30, 2024 and reviewed by the TAC by August 30, 2024. The table below shows the activity timeline for this program. Activities June-Aug 2024 Sept-Nov 2024 Dec 2024-Feb 2025 Full applications solicited, submitted and reviewed X Two Fellows selected and funds awarded to recipients X IRB applications and other regulatory paperwork X Research activities X X Manuscript preparation, oral presentation, and other dissemination activities X Career development activities, including coaching, research in progress, writing workshops and seminars X X X