HIV and Co-Infections Through the Lifecycle

Our Challenge

HIV/AIDS is the second leading cause of death in adolescents globally and, programmatically, adolescents are often an afterthought.  Teenagers have unique needs that need to be met with with age-appropriate behavioral and medical interventions, and our systems are not always serving them well.  They are often excluded from medical research because they are a difficult group to work with ethically and practically.  While AIDS-related deaths are decreasing in children, youth (age 20-24) and adults, they are increasing in adolescents.  Without intervention in early life, the implications of living with HIV can persist throughout the duration of a person’s lifecycle and into the next generation.

Our Response

Our Center has cultivated expertise in HIV/AIDS since its inception, particularly as it relates to women, adolescents, and children in resource-limited settings. We now leverage expertise in HIV to commit to a vision of transforming HIV testing and treatment approaches through integrated, innovative, and impactful research. We aim to serve as a hub for information, expertise, and collaboration in HIV research across the lifecycle.

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Our Priority Areas

We are committed to preventing mother-to-child HIV transmission by prioritizing biologic determinants of conveyance, mobile health (mHealth) interventions, and systematic evaluations of the programs currently in place.

Our priority for women also recognizes an obligation to address HIV acquisition in pregnant and postpartum women.  We center our research efforts for this population on pre-exposure prophylaxis (or PrEP) in pregnancy and repeat HIV testing.

Meeting the unique needs of adolescents living with HIV necessitates improvements to the quality, level of engagement, and adherence to HIV care.  We make these improvements by conducting research using simulated patient training, qualitative studies, continuing quality improvement, program evaluations, mHealth, social media, and service delivery evaluation.

Interventions during childhood have significant impact on the quality of HIV care throughout the reminder of a child’s life.  That’s why our research in this population area is focused on expediting diagnosis, understanding pathogenesis, optimizing treatment and long-term outcomes, and reducing mortality.

These research efforts focus on HIV testing models, financial incentives, immunologic and virologic determinants of acquisition and disease, co-infections, HIV-exposed uninfected children adherence and disclosure within care, treatment interruption, and accelerated ART.

Scientific Priority Co-Directors

Grace John-Stewart
MD, PhD
Professor, Global Health, Epidemiology, Medicine, and Pediatrics

Sylvia LaCourse
MD
Acting Assistant Professor, Medicine

Jennifer Slyker
PhD, MSc
Assistant Professor, Global Health
Adjunct Assistant Professor, Epidemiology

Anjuli Wagner
PhD
Postdoctoral Research Fellow, Global Health

Faculty Leads

Kristin Beima-Sofie
PhD, MPH
Acting Assistant Professor, Global Health

Sarah Benki-Nugent
PhD, MS
Clinical Assistant Professor, Global Health

Bhavna Chohan
PhD, MSc
Clinical Assistant Professor, Global Health;
Senior Research Scientist, Kenyatta National Hospital

Brandon Guthrie
PhD, MPH
Assistant Professor, Global Health and Epidemiology

Carol Levin
PhD, MSc
Clinical Associate Professor, Global Health;
Project Director, Global Health Cost Consortium

Melissa Mugambi
MD, PhD
Assistant Professor, Global Health

Jillian Pintye
PhD, MPH, RN
Acting Assistant Professor, Global Health

Keshet Ronen
PhD
Clinical Assistant Professor, Global Health

Technical Advisors

Jared Baeten
MD, PhD
Professor, Global Health, Epidemiology, and Medicine;
Vice Chair, Global Health

Carey Farquhar
MD, MPH
Professor, Global Health, Epidemiology, and Medicine;
Associate Chair for Academic Programs, Global Health

John Kinuthia
MBChB, MMed, MPH
Affiliate Associate Professor, Global Health;
Head of Research and Programs, Kenyatta National Hospital

Pamela Kohler
PhD, RN
Associate Professor, Global Health; Psychosocial and Community Health

Elizabeth Maleche-Obimbo
MBChB, MMed, MPH
Professor, Paediatrics and Child Health, University of Nairobi

Irene Njuguna
MBChB, MSc
PhD Candidate in Epidemiology;
Infectious Disease Researcher, Kenyatta National Hospital

Barbra Richardson
PhD
Research Professor, Biostatistics and [Adjunct] Global Health

Dalton Wamalwa
MBChB, MMed, MPH
Associate Professor, Pediatrics and Child Health, University of Nairobi

Kate Wilson
PhD, MPH
Clinical Assistant Professor, Global Health

Staff

Emily Begnel
MPH
Research Coordinator

Vrasha Chohan
BS
Research Scientist

Julia Dettinger
MPH
Research Scientist

Jaclyn Escudero
MPH
Research Coordinator

Laurén Gomez
MPH
Research Coordinator

Daniel Matemo
HND, MLS
Research Scientist, Kenyatta National Hospital

Jill Neary
MPH
Research Coordinator

Trainees

Dana Atkins
BS
MPH Student in Global Health

Danae Black
MPH
PhD Candidate in Epidemiology

Anna Larsen
MPH
PhD Student in Epidemiology

Zoe Rogers
BS
MPH Student in Global Health

Lisa Wiggins
BA
MPH Student

Junyi Zhang
BS
MPH Student in Global Health

Our Research

Sponsor:  National Institute of Child Health and Human Development (NICHD) (5R01HD089850)

Award Years:  08/01/2016 – 06/30/2021

Principal Investigator:  Grace John-Stewart

Co-Investigators:  Jennifer Slyker, Dalton Wamalwa, Pamela Kohler, Gabrielle O’Malley, Kristin Beima-Sofie

Trainees:  Danae Black

ATTACH aims to evaluate rates and co-factors of effective transition in HIV treatment programs in Kenya and to adapt, implement, and evaluate an Adolescent Transition Package (ATP) that combines an adapted US-based transition tool and a disclosure tool associated with improved disclosure outcomes in Namibia.

Click here to view the study protocol.

Sponsor:  Canadian Institutes of Health Research (20R11969)

Award Years:  04/01/2018 – 03/31/2019

Principal Investigator:  Jennifer Slyker

This study follows a cohort of 100 women and their children, and performs CMV qPCR of saliva, urine, breast milk, and blood samples, to identify >50 transmission events. We will then use whole viral genome NGS to definitively determine the source of each CMV transmission, and genotype T/F viruses. We will then use mathematical modeling to define the probability of transmission based on the viral load and genotypes of a given exposure.

Sponsor:  National Institutes of Health (UG3HD096906)

Award Years:  09/01/2018 – 08/31/2020

Principal Investigators:  Grace John-Stewart, Pamela Kohler

Co-Investigators:  Barbra Richardson (Biostatistics and Global Health, UW), Kristin Beima-Sofie, Katherine Wilson (Global Health/I-TECH, UW)

Adolescents (ages 10-19) experience disproportionately low retention, adherence and viral suppression compared to other age groups. The DiSC study aims to implement a combination data-driven intervention using a stepped care model to improve adolescent HIV engagement and clinical outcomes in Kenya. This generalizable systematic approach to deliver differentiated adolescent HIV care that integrates with diverse HIV care programs contributes to the acceleration of progress towards achieving 90-90-90 targets for adolescents.

Sponsor:  National Institute of Health (1R03AI140922)

Award Years:  07/06/2018 – 06/30/2020

Principal Investigator:  Alison Drake

This award supports leveraging data and archived data collected as part of Dr. Drake’s ongoing K01 study in Kenya, which aims to determine the optimal time to conduct repeat maternal HIV testing.  The specific aims are to: 1) externally validate two HIV risk score tools among a cohort of 4600 pregnant/postpartum women, 2) measure maternal HIV viral load and prevalence of TDR among 100 women with incident HIV infection during pregnancy/postpartum, and 3) identify biological and behavioral correlates of maternal HIV infection during pregnancy and postpartum. Together, data from the K01 and R03 studies will provide preliminary data to prepare for a large, implementation science trial of repeat maternal HIV testing coupled with targeted screening to determine eligibility for PrEP.

Sponsors:  UW/Fred Hutch Center for AIDS Research (CFAR) International Pilot Award and International AIDS Society Collaborative Initiative for Paediatric HIV Education and Research (IAS CIPHER)

Award Years:  01/16/2015 – 05/31/2017

Principal Investigator:  Jennifer Slyker (CFAR), Irene Njuguna (IAS CIPHER)

Co-Investigators:  Grace John-Stewart, Anjuli Wagner

Staff:  Jill Neary

Trainees:  Dana Atkins, Junyi Zhang

This pilot study will evaluate the acceptability, feasibility and costs of offering financial incentives to HIV-infected parents to motivate testing of their HIV-exposed children. 60 parents of children <12 years old who are utilizing HIV treatment services at Kenyatta National Hospital (Nairobi, Kenya) will be randomized to receive $5, $10, or $15 cash payment contingent upon completing pediatric HIV testing. A post-test questionnaire will evaluate acceptability, feasibility and motivational mechanisms of the intervention. Data will be used to support future submission of a larger R01-scale grant evaluating effectiveness of the intervention.

Click here to view the study protocol.

Sponsor:  National Institutes of Health (5R01HD094718)

Award Years:  09/01/2017 – 06/30/2022

Principal Investigators:  Grace John-Stewart, Dara Lehman (Fred Hutchinson Cancer Research Center)

Co-Investigators:  Jennifer Slyker, Sarah Benki-Nugent

The study will model longitudinal reservoir dynamics, and determine effects of infant timing of HIV acquisition, ART timing, and the influence of infant immune activation, ADCC, and NK population characteristics on reservoir decline and size. These studies will provide novel data on reservoir dynamics during infancy and early childhood from sub Saharan Africa and will elucidate potential influence of immune activation, ADCC, and natural killer phenotype in reservoir containment, and ultimately inform intervention strategies for improved long-term management and reservoir control in HIV infected children.

Sponsor:  World Health Organization (PO 202170778)

Award Years:  04/01/2018 – 12/31/2019

Principal Investigator:  Alison Drake

Co-Investigators:  Brandon Guthrie (Global Health and Epidemiology, UW) Christine Khosropour (Epidemiology, UW), David Katz (Global Health and Medicine, UW), Anjuli Wagner

We aim to support the World Health Organization (WHO) HIV Department Key Population and Innovative Prevention (KPP) unit’s work on HIV testing services. These tasks focus on three key areas: (1) supporting implementation of partner notification services (PNS) globally, (2) gathering and synthesizing evidence and conducting scoping reviews in order to prepare for the 2019 update to the WHO Consolidated Guidelines on HIV Testing Services, (3) inform implementation of HIV and syphilis testing strategies in maternal and child health programmes, and (4) guide programming for integration of HIV testing into family planning service delivery.

Sponsor:  John Hopkins University/National Institutes of Allergy and Infectious Diseases and of Child Health and Human Development (PO#2002131144; Prime 5UM1AI068632)

Award Years:  02/01/2014 – 11/30/2019

UW Consortium Principal Investigator:  Grace John-Stewart

Leadership and Operations Center of the International Maternal Pediatric Adolescent AIDS Clinical Trials (LOC-IMPAACT) support multiple research priorities by conducting clinical trials of new drugs and vaccines in vulnerable populations.  The trials will determine the safety, dosing, and efficacy of these interventions for the prevention and treatment of HIV and its co-morbidities/co-infections thereby reducing morbidity/mortality worldwide.

Sponsor:  Thrasher Research Fund

Award Years:  09/01/2015 – 08/31/2019

Principal Investigator:  Grace John-Stewart

Co-Investigators:  Sylvia LaCourse, Elizabeth Maleche-Obimbo, Barbra Richardson (Biostatistics and Global Health, UW)

This randomized controlled trial aims to determine if isoniazid preventative therapy (IPT) prevents primary Mycobacterium tuberculosis (Mtb) infection in HIV-exposed uninfected infants in Kenya.

Click here to view the study protocol.

Sponsor:  National Institute of Child Health and Human Development (5R01HD090460)

Award Years:  05/01/2014 – 04/30/2019

Principal Investigator:  Grace John-Stewart

Co-Investigators:  Jennifer Unger, Alison Drake, Keshet Ronen

This randomized controlled trial is comparing 1-way SMS vs 2-way SMS vs control to improve virologic suppression in HIV-infected peripartum women.

Sponsor:  National Institutes of Health (1R21AI138618)

Award Years:  06/06/2018 – 05/31/2020

Principal Investigator:  Jillian Pintye

The proposed study aims to quantify maternal-to-infant transfer during pregnancy for a variety of ARVs by employing a novel pharmacokinetic evaluation using maternal and neonatal hair in an unprecedented cohort. We will use validated assays developed by our group to measure ARV levels in hair samples collected at birth from mother-infant pairs enrolled in the Surveillance Monitoring for ART Toxicities Study in HIV-uninfected Children Born to HIV-infected Women (SMARTT Study), a Pediatric HIV/AIDS Cohort Study (PHACS)-funded prospective study designed to evaluate the effects of ARV exposure on infants born to HIV-infected mothers in the U.S.  Our results will improve understanding of maternal-to-infant transfer for common ARVs used during pregnancy with ultimate implications for worldwide efforts to prevent perinatal HIV transmission with maximum efficacy and minimal toxicity.

Sponsor:  National Institutes of Health (1R34MH114834)

Award Years:  07/01/2018 – 04/30/2021

Principal Investigator:  Brandon Guthrie

Co-Investigators:  Keshet Ronen, Jennifer Unger, Megan Moreno (Pediatrics, University of Wisconsin-Madison)

This planning grant will pilot a mHealth framework that uses a combination of group peer support and one-to-one communication with a healthcare provider specifically trained in youth HIV care.

Sponsor:  National Institute of Allergy and Infectious Diseases (5K01AI116298)

Award Years:  07/10/2015 – 06/30/2020

Principal Investigator:  Alison Drake

Mentors:  Grace John-Stewart, Kenneth Gimbel-Sherr (Global Health and Epidemiology, UW)

Sponsor:  Christian Health Association of Kenya (NU2GGH002034)

Award Years:  10/01/2018 – 03/31/2019

Principal Investigator:  Grace John-Stewart

Co-Investigators:  Sarah Benki-Nugent, Kristin Beima-Sofie, Alison Drake, John Kinuthia, Christine McGrath

This is a Collaborative Agreement to promote international research efforts and improve the health of Kenyans through medical and preventative health measures. The scope of work includes completion of study activities for the three program evaluations listed below. Specifically, this includes completion of data collection activities, data cleaning and analyses, dissemination of results through report writing and manuscript development.  The funding supports the following studies:

1. Impact of ART Adherence and Early Infant HIV Diagnosis on the Effectiveness of Option B+ in Kenya (Option B+)
2. Prevalence, Cofactors, and Types of Family Planning Methods Used by HIV-infected Women in HIV Care Programs in Kenya (FP)
3. Assessment of Adolescents HIV Care in Large HIV Treatment Programs in Kenya (PHASE)

Sponsor:  National Institutes of Health (01R01AI142647)

Award Years:  01/01/2019 – 12/31/2023

Principal Investigator:  Grace John-Stewart, Cheryl Day (Emory University)

Co-Investigators:  Sylvia LaCourse, Jennifer Slyker, Barbra Richardson, Dalton Wamalwa, Elizabeth Maleche-Obimbo

Staff:  Jaclyn Escudero

The proposed study will utilize specimens from unique cohorts of HIV-infected, HEU, and HIV-unexposed (HUU) children to determine predictors of anti-mycobacterial immunity (including HIV exposure, HIV infection, antiretroviral treatment, and other factors), the influence of HIV exposure or infection on ‘trained immunity’, and the effects of this immunity on susceptibility to TB.

This study uses data from the Impact of maternal HIV on Mycobacterium tuberculosis infection among peripartum women and their infants (MITIPS) study (PI: LaCourse). Click here to read the study protocol.

Sponsor:  National Institute of Health (5R01AI125498-03)

Award Years: 05/01/2016 – 04/30/2021

Principal Investigator:  Grace John-Stewart

Co-Investigators:  Jared Baeten, Ruanne Barnabas, Sarah Gimbel-Sherr, Barbra Richardson

Staff:  Julia Dettinger, Laurén Gomez

PrEP Implementation for Mothers in Antenatal Care (PrIMA) is a cluster randomized trial to determine the best model for optimized PrEP delivery in pregnancy within maternal-child health systems.

Click here to view the study protocol. 

Sponsor:  PEPFAR DREAMS/National Institute of Child Health and Human Development (5R01HD094630)

Award Years:  09/01/2017 – 06/30/2022

Principal Investigators:  Grace John-Stewart, Pamela Kohler

Co-Investigators:  Barbra Richardson, Jennifer Unger, Jillian Pintye, Jane Simoni (Psychology, Global Health, and Gender, Women, and Sexuality Studies, UW)

Trainees:  Anna Larsen, Zoe Rogers

PrEP Implementation for Young Women and Adolescents (PrIYA) seeks to programmatically evaluate implementation, and determine best practices for providing PrEP to young women and adolescent girls in maternal-child health (MCH) and family planning (FP) clinics.

Sponsor:  National Institutes of Health (1R21HD089821)

Award Years:  08/15/2018 – 07/31/2020

Principal Investigator:  Jennifer Slyker

Co-Investigators:  Grace John-Stewart, Dalton Wamalwa

Staff:  Lauren Gomez

This study involves the use of data and archived specimens from the completed RCT Pediatric Urgent Start of HAART (PUSH), Grant: 5R01HD023412-25; PI: John-Stewart.  This study aims to determine the impact of cytomegalovirus (CMV) viremia on mortality and duration of hospital stay, response to ART initiation, and immune activation and inflammation among children diagnosed with HIV infections while critically ill.

Click here to view the PUSH study protocol.

Sponsors:  Thrasher Research Fund and UW/Fred Hutch Center for AIDS Research (CFAR) New Investigator Award

Award Years:  03/01/2017 – 02/28/2019

Principal Investigator:  Grace John-Stewart (Thrasher), Anjuli Wagner (CFAR NIA)

Co-Investigators:  Anjuli Wagner, Irene Njuguna

This study aims to validate saliva-based HIV testing in children and to develop and test a video-based pre-test information session for outpatient HIV testing.

Sponsor:  Fred Hutchinson Cancer Research Center (0000966758)

Award Period:  09/06/2017 – 06/30/2019

Principal Investigator:  Jennifer Slyker

Co-Investigators:  Grace John-Stewart, Barbra Richardson, Dalton Wamalwa

Staff:  Emily Begnel, Bhavna Chohan

The Virome MTCV study is a prospective cohort study of both HIV-infected and -uninfected women and their infants. This study will characterize the determinants of mother-to-child virome transmission and how components of the virome affect infant health. There will be a special emphasis on cytomegalovirus (CMV) due to its prevalence and known importance for human health.

This award also includes a protocol component, which involves testing archived breast milk samples from past studies to evaluate how HIV disease progression and ART use impact the composition of the maternal virome in breast milk.

Sponsor:  UW/Fred Hutch Center for AIDS Research (CFAR) International Pilot Award

Award Years:  01/2018 – 01/2019

Principal Investigator:  Anjuli Wagner

Co-Investigator:  Irene Njuguna

Trainees:  Hilary Vonckx, Lisa Wiggins

This one year project aims to test new technology-based approaches to engage adolescents who do not typically seek HIV preventative and treatment services, and determine whether adolescents recruited via WhatsApp are demographically distinct from those identified in a clinical setting.  This project will test respondent-driven sampling—a social network-based strategy used to collect data from hard-to-reach populations who may fear being identified with stigmatized behavior, such as injection drug users, female sex workers, and men having sex with men—in hopes of reaching adolescents from diverse backgrounds and health-seeking behaviors.  They will also compare the WhatsApp virtual focus groups to traditional in-person focus groups in terms of content and depth of responses, and costs.