HIV PREVENTION TRIAL DESIGN PROJECT

Towards a feasible regulatory path for new PrEP products

In 2019, under the umbrella of the PrEP Program, the HIV Prevention Trial Design Project was formed and builds on previous working groups and public meetings. The project is funded by the Bill & Melinda Gates Foundation in addition to industry sponsors. It uses the “totality-of-evidence” framework and adopts innovative trial designs, including a counterfactual estimate of HIV incidence in communities in which PrEP clinical trials are conducted.

The overall goal of the project is to develop a path to provide convincing evidence of a new PrEP product’s effectiveness and safety, maintain scientific rigor, and create a feasible/pragmatic path for development.

CURRENTLY ACTIVE WORKING GROUPS

WORKING GROUP ACCOMPLISHMENTS AND PROGRESS

STI-HIV Incidence Correlation in MSM: The Forum and University of Washington in collaboration with Public Health England (PHE) are using the data from the Genitourinary Medicine Clinic Activity Dataset (GUMCAD) STI Surveillance System to assess the temporal correlation between trends in rectal gonorrhea and HIV diagnoses in MSM.

GUMCAD is a mandatory surveillance system in England that collects data on STI tests, diagnoses and services from all commissioned sexual health services.

Kidist Zewdie, an Epidemiology PhD student at the University of Washington School of Public Health, conducted the analysis and will present preliminary findings at an upcoming conference.

Recency Assay Working Group: The goal of the group is to build a counterfactual of what the HIV incidence would have been in the absence of PrEP. The objectives are to determine the potential usefulness of recency assays for estimating background HIV incidence and facilitate discussions on the regulatory path for the development of improved HIV incidence assays, if needed. Two subgroups focus on (1) Assay Calibration and Interpretations and (2) Clinical Trial Designs.

Prevention Trials in Women Working Group: This working group focuses on specific issues for trials in women and adolescent girls at high risk for HIV-infection. Specifically, How can the recency assay approach for cross sectional incidence estimates be best used in trials in women and adolescent girls? To what extent can STI’s be used as an indicator of HIV risk? And what are the best surveillance and other tools to confirm results obtained by recency assay studies?

OUTPUTS

• Discussions on the regulatory path for the development of improved HIV incidence assays, if needed
• Consensus to use LAg-avidity assay + VL algorithm to measure baseline HIV incidence
• Consensus to list advantages and disadvantages of including different variables in the testing algorithm; consideration of ARV testing in algorithm is population specific
• Collaboration with PHE GUMCAD database; abstract to be submitted to R4P Conference and peer-received journal publication. Analysis initiated by Kidist Zewdie, mentored by Jared Baeten. Kidist Zewdie is funded through the Forum’s Intern & Fellows program with support from Gilead

OTHER HIV FORUM ACTIVITIES

Public Meetings: The objective is to focus on community expert inputs on PrEP clinical trial designs for different populations in different regions. Public meetings initially planned as in person meetings for the US, EU, and SSA will be converted in a series of web discussions with focused topics. In the first series, web discussions will address issues that regulators, particularly the FDA and EMA, want to have comments on, in addition to community input on these issues. In another series, issues for other regions, such as Sub-Saharan Africa, will be addressed. This is being led by the Public Meeting Planning Committee. If you would like to participate in the meetings, please contact Dr. Tamar Tchelidze.

IN-DEVELOPMENT WORKING GROUPS

• Innovation in statistical approaches
• Role of animal models and PK/PD studies in “totality-of-evidence”

REGULATORY SCIENCE INTERNSHIP AND FELLOWSHIP PROGRAM

Joseph Lau, UC Berkeley MPH ’21, Graduate Intern

Joseph is a graduate student intern at the Forum for Collaborative Research. He is currently pursuing his Masters of Public Health with an emphasis in infectious diseases and vaccinology at UC Berkeley. He completed his BS in Biology with a concentration in microbiology from San Francisco State University in 2017. He had the opportunity to join a plant bacterial genetics lab studying Sinorhizobium meliloti, a gram-negative leguminous plant symbiont. After graduating from San Francisco State University in January 2017, he worked at Vitalant Research Institute, under Dr. Mars Stone, director of the Viral Reference Lab and Repository Core. He was a lab manager/study coordinator for the Reservoir Assay Validation and Evaluation Network study, a study where leukapheresis-derived PBMCs and plasma panels are distributed to labs that are developing or performing HIV reservoir assays to evaluate and compare performance characteristics that could be used in clinical research studies. 

Tinkhani Mbichila, MD, UC Berkeley MPH ’20, Graduate Intern

Tinkhani is a graduate student intern under the HIV Forum at the Forum for Collaborative Research. He is currently pursuing an MPH degree in Epidemiology at UC Berkeley. Tinkhani is a medical doctor and public health researcher with experience in conducting clinical trials in infectious diseases. After graduating from the University of Malawi with a Doctor of Medicine degree, he worked with the Ministry of Health, providing clinical care in infectious diseases. In 2016, he joined the University of North Carolina research project leading PrEP safety and efficacy clinical trials as a co-investigator under the HIV Prevention Trials Network (HPTN). These trials tested novel PrEP agents of infusible, broadly neutralizing monoclonal antibodies (VRC01), and injectable integrase inhibitor (cabotegravir) against HIV-1 acquisition in sub-Saharan African women. Tinkhani plans to use the experience at the Forum to launch a career that will help him contribute towards improving global health through research and application of evidence in global policy and practice.

Click here to learn more about the program

To learn more about the HIV Forum, please contact Dr. Tamar Tchelidze