R01AI152897

Next-Generation Algorithms Using Multiple Biomarkers for Precise Estimation of HIV Infection Duration and Population-Level Incidence - Summary

Given the central role of HIV incidence estimation in both surveillance and evaluation of HIV prevention programs, it is essential to have reliable, inexpensive, and usable methods for quickly estimating incidence in near-real time. This proposal aims to advance that goal by capitalizing on our recent developments in using a spectrum of biomarker data and HIV surveillance data to compute the complete posterior probability distribution of the time since infection for recently diagnosed persons.

We posit that such estimates contain not only more accurate information about the time of infection than standard binary classification (recent/long-term), but that it also gives realistic confidence bounds on HIV incidence estimates as it appropriately takes biomarker measurements and patient variation into account. We further posit that an accurate HIV incidence estimate must take three components into account: 1) the multi-assay algorithm (MAA)-adjusted time of infection (rather than the date of diagnosis or simple recent/non-recent binary classification); 2) the number of undiagnosed persons living with HIV (PLHIV) at a certain time (which may be diagnosed later); and 3) the number of HIV positive individuals that move into the study population.

Specifically, we will:

1) Develop laboratory protocols and algorithms for measuring and modeling individual biomarkers for probabilistic estimation of time of HIV infection.
2) Combine biomarkers into a generalized MAA for improved estimation of time of HIV infection and HIV incidence.
3) Apply the new MAA to determine the duration of infection and estimate HIV incidence in different human populations.

Using large data, in total >13,000 patients with up to 7 different biomarkers determined, from Sweden, USA, South Africa, and Zimbabwe, we will establish longitudinal and single-time point training data, as well as validation data, to develop validated, publicly available methods to estimate: 1) the full distribution of time since infection for individual PLHIV; and 2) population-level HIV incidence based on either study-based samples or existing surveillance systems, and changes thereof over time, using new biomarkers, algorithms, and models.

Triad National Security

TO ASSIST PUBLIC AND PRIVATE NONPROFIT INSTITUTIONS AND INDIVIDUALS TO ESTABLISH, EXPAND AND IMPROVE BIOMEDICAL RESEARCH AND RESEARCH TRAINING IN INFECTIOUS DISEASES AND RELATED AREAS, TO CONDUCT DEVELOPMENTAL RESEARCH, TO PRODUCE AND TEST RESEARCH MATERIALS. TO ASSIST PUBLIC, PRIVATE AND COMMERCIAL INSTITUTIONS TO CONDUCT DEVELOPMENTAL RESEARCH, TO PRODUCE AND TEST RESEARCH MATERIALS, TO PROVIDE RESEARCH SERVICES AS REQUIRED BY THE AGENCY FOR PROGRAMS IN INFECTIOUS DISEASES, AND CONTROLLING DISEASE CAUSED BY INFECTIOUS OR PARASITIC AGENTS, ALLERGIC AND IMMUNOLOGIC DISEASES AND RELATED AREAS. PROJECTS RANGE FROM STUDIES OF MICROBIAL PHYSIOLOGY AND ANTIGENIC STRUCTURE TO COLLABORATIVE TRIALS OF EXPERIMENTAL DRUGS AND VACCINES, MECHANISMS OF RESISTANCE TO ANTIBIOTICS AS WELL AS RESEARCH DEALING WITH EPIDEMIOLOGICAL OBSERVATIONS IN HOSPITALIZED PATIENTS OR COMMUNITY POPULATIONS AND PROGRESS IN ALLERGIC AND IMMUNOLOGIC DISEASES. BECAUSE OF THIS DUAL FOCUS, THE PROGRAM ENCOMPASSES BOTH BASIC RESEARCH AND CLINICAL RESEARCH. SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM EXPANDS AND IMPROVES PRIVATE SECTOR PARTICIPATION IN BIOMEDICAL RESEARCH. THE SBIR PROGRAM INTENDS TO INCREASE AND FACILITATE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, TO INCREASE SMALL BUSINESS PARTICIPATION IN FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. THE SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM STIMULATES AND FOSTERS SCIENTIFIC AND TECHNOLOGICAL INNOVATION THROUGH COOPERATIVE RESEARCH AND DEVELOPMENT CARRIED OUT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO FOSTER TECHNOLOGY TRANSFER BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. RESEARCH CAREER DEVELOPMENT AWARDS SUPPORT THE DEVELOPMENT OF SCIENTISTS DURING THE FORMATIVE STAGES OF THEIR CAREERS. INDIVIDUAL NATIONAL RESEARCH SERVICE AWARDS (NRSAS) ARE MADE DIRECTLY TO APPROVE APPLICANTS FOR RESEARCH TRAINING IN SPECIFIED BIOMEDICAL SHORTAGE AREAS. IN ADDITION, INSTITUTIONAL NATIONAL RESEARCH SERVICE AWARDS ARE MADE TO ENABLE INSTITUTIONS TO SELECT AND MAKE AWARDS TO INDIVIDUALS TO RECEIVE TRAINING UNDER THE AEGIS OF THEIR INSTITUTIONAL PROGRAM.

93.855 - Allergy and Infectious Diseases Research

National Institute of Allergy and Infectious Diseases (NIAID) [HHS - NIH]

Los Alamos, New Mexico 875450001 United States

Single Zip Code

Novel Biomarkers for the Development of HIV Incidence Assays with Improved Specificity (R01 Clinical Trial Optional) (PA-18-753)

Amendment Since initial award the total obligations have increased 395% from $705,028 to $3,487,866.