Global Viral Oncology Research and Training Programs

Zambia faces epidemic proportions of HIV/AIDS, and 1.2 million people – or 12% of the country’s adult population – are infected by this disease.

The widespread availability of free antiretroviral treatment has increased the lifespan of HIV-1-infected individuals, leading to prolonged chronic immunosuppression and increased cases of HIV-associated cancers. However, the country’s efforts to prevent, diagnose, and manage cancer in Zambia have been hindered by a lack of laboratory facilities, insufficient cancer research infrastructure, and a shortage of trained personnel.

AMTRIP performs research and training in molecular detection and characterization of AIDS and non-AIDS defining malignancies in Zambia.

1. Enhances pathology services
2. Develops molecular tools and technologies
3. Trains Zambian fellows in cancer research using molecular techniques, including viral oncology, next generation sequencing, and cancer genomics and bioinformatics

• Basic research degree training in infectious agents and disease pathology
• Degree and postgraduate training in HIV/AIDS and AIDS-associated malignancies
• Postgraduate training in basic research, cancer genomics/bioinformatics, cancer epidemiology, pathology programs for AIDS, and associated malignancies
• Short-term laboratory skills training in HIV/AIDS-associated diseases and malignancies
• In-country training

• Enhanced collaborations among institutions 
• Enhanced research infrastructure and research capacity in Zambia 
• Technology transfer 
• Establishment of new partnerships 
• Mentorship from former trainees, who are establishing independent research careers 

• In 2002, established a research clinic within University Teaching Hospital campus, the main reference hospital in Zambia.

• In 2005, dedicated and expanded a newly equipped research laboratory.

• In 2011, established immunohistochemistry laboratory in pathology. 

• Headed and staffed by Fogarty trainees.

• Staffed by University of Zambia (UNZA) and UTH research personnel, including nurses, data teams, medical personnel – many of whom are trained through the Fogarty AIDS International Training and Research Program (AITRP). 

• Partners with the CDC/US President's Emergency Plan for AIDS Relief (PEPFAR).

Tanzania faces an HIV epidemic with a prevalence of 4.5% among its population. Certain areas face higher proportions, such as in Njombe with a prevalence of 11.4%. Young women and adolescent girls make up 80% of all new HIV infections.

Considerable advancements in HIV/AIDS awareness and treatment have led to a significant increase in antiretroviral treatment and viral load suppression among Tanzanians 15 years and older.

TAMTRP is critical to prepare ORCI and Tanzania for the era of personalized and precision cancer medicine, which will utilize cancer genomics for cancer detection, diagnosis, prevention, and treatment. It provides important insight into the understanding and prevention of HIV-associated and non-HIV-associated malignancies in Tanzania, and reciprocally, in the US.

TAMTRP is committed to enhancing the HIV-associated malignancies (HIVAM) and non-HIVAM research capacity of the major cancer research institution in Tanzania – ORCI. TAMTRP’s scientific focus is research and training on cancers associated with an infectious etiology, especially those commonly encountered in Tanzania. The program builds onto existing collaboration to enhance the number of trained cancer researchers in Tanzania to prepare them for the future of HIV-associated cancer diagnostics and research in cancer genomics and therapy.

TAMTRP also: 

1. Provides training for two PhD and four MS candidates in a relevant cancer research field. Fellows are selected from ORCI to earn their graduate degree from LSUHSC-NO in cancer biology, cancer genomics and bioinformatics, biostatistics, and epidemiology, or to pursue an MMed or PhD degree in oncology, biomedical sciences, or public health at ORCI/MUHAS.
   
   
2. Provides medium-term technical training in molecular pathology, cancer biology, bioinformatics, genomics, biostatistics, biobanking, cancer registry, and clinical and translational research.
   
   
3. Delivers technical workshops designed to enhance basic, clinical, implementation, genomics, bioinformatics, computation genomics, epidemiology, and biostatistics.

TAMTRP has four training tracks:  

1. Clinical trials methodologies and management 

2. Public health operational and translational research, including cancer prevention, biostatistics and data management, epidemiology, cancer registry, and biobanking 

3. Laboratory-based cancer biology research, including molecular biology/virology, pathology, diagnostics, viral oncology, and immunology 

4. Cancer genomics and bioinformatics, including next generation sequencing, data management, big data analytics, and computational genomics 

With the rapid rise in the number of people that test positive for HIV, there are many who are afflicted with AIDS-associated malignancies, such as Kaposi’s sarcoma, lymphomas, and cervical carcinoma. This has resulted in a strong need to train researchers and professionals in developing countries where it currently is or will be a major health issue.

We are creating a strong core of specialists trained in building capacity to prevent the transmission of HIV-associated and AIDS-associated diseases. Our program focuses on developing skills to apply molecular techniques and novel medical science approaches to prevent transmission, diagnose, and treat HIV and AIDS-related diseases to address local and global health needs for effective disease prevention strategies.

AITRP provides specialized training opportunities in HIV/AIDS-related and AIDS-related research in the US lasting from 3 months to up to 4 years. At the end of the training period, candidates return to their home country as researchers to strengthen research initiatives and establish long-term collaboration between US investigators and foreign researchers in the fight against the AIDS epidemic.

Program components include:

Basic Research

• Intensive academic instruction at the University of Nebraska leading to MS and PhD degrees in biomedical sciences/virology or an MPH degree in the School of Public Health.
  
  
• Biomedical research rotations at the University of Nebraska – Lincoln, the University of Alabama at Birmingham, and the University of Miami to investigate the role of HIV, human papilloma virus, Karposi’s sarcoma herpesvirus (KSHV), and Epstein-Barr virus (EBV) in the development of AIDS-associated malignancies and train in advanced laboratory methods to detect pathogens and monitor HIV genotypes and drug resistance.

Clinical Research

• Rotations in the clinical management of AIDS, antiviral treatments, and AIDS-associated malignancies at the University of Miami where faculty trainers specialize in working with two distinct segments of a population – infected adults and infected children.

Epidemiology and Socio-behavioral Research (Including Biostatistics)

• Training in epidemiology and behavioral aspects of HIV/AIDS and AIDS-associated malignancies at the University of Nebraska – Lincoln and the University of Nebraska Medical Center to improve in-country data analysis and facilitate the development and evaluation of public health intervention strategies.

Kaposi sarcoma is one of the most prevalent cancers in people living with HIV and a significant health concern in Africa. In 2020, Africa made up 73% of cases and almost 87% of deaths from KS.

The goal of KEAAP is to understand why Kaposi sarcoma is still prevalent in Africa in HIV viral suppressed individuals.

It aims to research the hypothesis of HIV chronic infection leading to immune senescence against KSHV infection, leading to KS, and enabling the presence of higher distributions and size of KSHV-infected reservoirs in HIV+ viral suppressed KSHV-infected individuals.

KEAAP consists of three projects: 

1. Implementation of recruitment, diagnosis, and linking to care cascade (at both sites) 

2. KSHV immune response (at both sites) 

3. KSHV reservoirs (only in Zambia) 

The autopsies and tissue analyses set up in Zambia help train and build infrastructure in Tanzania. The implementation, staging, and linkage to care project are carried out in both countries.

Kaposi sarcoma is the second most prevalent cancer among Zambians, with an incidence rate of 16 per 100,000 residents. Ocular surface squamous neoplasia (OSSN) is also common in Zambia, and the incidence rate is on the rise.

Zambia AIDS Malignancies Diagnosis and Pathogenesis Program’s (ZAMDAPP’s) goal is to develop a sustainable cancer research infrastructure in virology oncology, biostatistics and epidemiology, and cancer diagnostics within Zambia and support interdisciplinary research projects on two HIV/AIDS-associated malignancies – Kaposi sarcoma and ocular surface squamous neoplasia – led by trained Fogarty fellows.

ZAMDAPP also: 

• Develops cancer research infrastructure at the University of Zambia (UNZA), University Teaching Hospital, and the Cancer Diseases Hospital (CDH) through the establishment and enhancement of two research core facilities
• Provides an opportunity for former Fogarty fellows to lead research projects in two prevalent AIDS-associated malignancies, KS and OSSN, with the support of US partners and core facilities
• Develops a pipeline of next generation Zambian cancer researchers through in-country workshops, pilot project funding, and short-term US technical training

Research projects include: 

Impact of Co-factors on Antiretroviral Treatment Outcomes in Early-Diagnosed Kaposi’s Sarcoma Patients Project Leaders

Overall goals are to implement a strategy in Zambia to identify and diagnose KS early as well as couple diagnosis to prospective investigations of the underlying cause(s) of antiretroviral therapy (ART) treatment successes and failures.

We hypothesize that factors such as HIV and KSHV viral load, genetics, and soluble proteins, or immunological parameters that preexist the administration of ART to KS patients, impact the outcome of early KS therapy with ART alone.

• Aim 1: Develop and implement a Zambian early KS recognition, referral, and diagnosis network.
• Aim 2: Correlate parameters of HIV-1 and KSHV disease with the outcome of ART treatment of early KS.
• Aim 3: Identify immunologic biomarkers of early KS ART treatment success or failure.

Pathological Diagnosis and Etiology of Ocular Surface Squamous Neoplasia in Zambia

Our goal is to identify factors that differentially associate with the pathogenesis of OSSN in HIV-1-infected individuals. We hypothesize that HIV-1 co-infection promotes infection by specific HPV genotypes, which correlate with increased rates of OSSN.

• Aim 1: Recruit Zambian patients with OSSN and characterize the associated risk factors.
• Aim 2: Investigate whether mucosal or cutaneous HPVs are differentially co-associated with OSSN or with tumors stratified by tissue type or tumor stage.
• Aim 3: Determine the genotypes of HPV present in different stages of OSSN tumors in Zambian HIV-1+ and HIV-1- patients.

• Developed an umbrella research program led by local partner
• Established active interphasing with D43 training programs
• Enhanced pathology research capacity
• Enhanced lab equipment
• Developed next generation of cancer researchers through the Emerging Global Leader Program and as lead for research projects
• Trained actively publishing researchers who have become mentors
• Developed regional collaborations through the U54 network
• Participated in research on COVID-19 and cancers in sub-Saharan Africa