COVID-19 and Tuberculosis
As SARS-CoV-2 spread, the HVTN was tapped to apply its clinical, statistical and operational infrastructure to rapidly design, implement and analyze the U.S. Government-supported Phase 3 clinical trials of COVID-19 vaccines.
The COVID-19 Prevention Network (CoVPN), funded by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH), was formed in spring 2020 to create a coordinated, efficient and scientifically rigorous approach to developing the COVID-19 vaccines in order to help end the pandemic.
In partnership with the AIDS Clinical Trials Group (ACTG) and International Maternal Pediatric Adolescent AIDS Clinical Trials Network (IMPAACT), the HVTN is conducting an integrated clinical trials program for TB that includes immunological, microbiological and diagnostic technologies. This will enhance the TB vaccine field globally by evaluating the safety and immunogenicity of TB vaccines for all age groups. We seek to identify vaccines that (1) prevent TB infection, (2) prevent progression from TB infection to disease, and (3) reduce the risk of unfavorable treatment outcomes, particularly treatment failure and recurrent TB, and post-treatment morbidity and mortality when used adjunctively with TB treatment.
Our approach of integrated science gives us the ability to look at the whole picture of HIV prevention, enabling us to not only fine-tune our study vaccines, monoclonal antibodies (mAbs) and recruiting methods, but also to prepare for the day when an effective vaccine is found.
The questions we ask go far beyond, “Does this vaccine/mAb protect people from HIV/AIDS?”
Research Areas
Vaccinology & Immunology
We incorporate new immunologic concepts into our measurement and analysis of human responses to vaccines.
The HVTN maintains a vigorous program to facilitate the development and assessment of novel candidate vaccines and passive immunization approaches. We are leading the field in designing, validating and implementing advanced immunological assays to accurately and reproducibly evaluate the broad range of immune responses elicited by candidate HIV vaccines. Our standardized datasets provide a means to compare vaccine regimens in great detail and identify the most promising candidates for further studies of efficacy.
Our Laboratory Center, which include multiple labs in the United States and South Africa, has developed over 20 assays to support international HVTN clinical trials, and continues to evolve our approaches as new methods become available — descriptions of Laboratory Center assays.
Our laboratories have developed, standardized, qualified and validated several methods of sampling, processing and testing samples from trial participants, allowing the HVTN to evaluate immune responses in different tissues and in blood. Understanding immune responses in different tissues and parts of the body can help researchers design vaccines that will target HIV at the point of entry.
Statistics
We integrate biostatistics, bioinformatics, and computational biology to design and analyze clinical trials that provide definitive answers to questions about the potential of experimental vaccines.
The HVTN Statistical and Data Management Center (SDMC) develops statistical methods for clinical trial design and analysis. Their work includes creating a framework to understand immune responses and developing new models for defining vaccine effects. Their achievements to date include:
- Development of new trial design models (such as Phase 2b trials) to efficiently evaluate vaccines
- Development of new trial designs in response to developments in the field (for example, efficacy trials in the context of pre-exposure prophylaxis [PrEP] use)
- Generation of sophisticated statistical methods for analyzing multifactorial immunoassays
- Methods for analyzing the safety, immunogenicity, and efficacy of study products in the context of social, behavioral, demographic, and genetic differences among participants
Behavioral Science
We incorporate new approaches from behavioral science to improve study volunteer recruitment, assess behavioral risks for HIV acquisition, and compare those risks with HIV incidence rates or vaccine efficacy.
Accurate behavioral measures are important for many reasons, including:
- They help us decide who can be in our clinical trials (some trials only enroll people whose risk of HIV infection is low; some trials look for people whose risk is high)
- They help us determine what might affect our trial results besides the vaccine itself
- They help us determine whether the participants in the study and control groups are at similar risk at the beginning of the study, and provide a measure of whether they remain comparable over time
- They help us determine patterns of behavior change during a trial, and can indicate differences in risk that might impact exposure to HIV
- If a vaccine is efficacious, behavioral risk data can help us determine if different behaviors affect the efficacy of the vaccine
- Behavioral data can help us estimate how much other biomedical interventions (such as PrEP) are used by the participants and in their segment of the population
- They help us assess what risk behaviors should be considered when testing vaccine efficacy and correlates of protection.
Social Science
We use social science concepts to look at human interactions, which helps us improve our engagement with communities and recruitment of study volunteers. We use social science models and theories to explore the many social factors that might impact trial design and implementation.
The social sciences look at the interactions of humans with each other, in large and small groups. The HVTN uses theoretical models and evidence from social science to look at factors that may have an effect on the efficacy of our study vaccines, and to improve our strategies for engaging communities and recruiting study volunteers.
Our social science work benefits our mission in many ways, including:
- Understanding what impacts people’s perceptions of vaccine research and willingness to participate in HIV vaccine clinical trials
- Identifying innovative community engagement approaches and outcome measures
- Improving participation and retention rates
- Improving adherence to study procedures and visits
- Improving dissemination and acceptance of efficacious interventions