P01AI169615

Understanding reservoir dynamics through analysis of viral decay processes - Summary - Overall, to understand HIV-1 reservoir dynamics, we must understand how the reservoir is formed. The overall goal of this research program is to study dynamics of the latent reservoir through single cell analysis of the viral decay processes that determine the composition of the reservoir.

Seminal studies by co-investigator Alan Perelson showed that following initiation of combination antiretroviral therapy (ART), plasma virus levels decay rapidly in a striking biphasic fashion. These studies established that in untreated people living with HIV-1 (PLWH), most of the virus in the blood is produced by infected cells that die or transition to a non-productive state of infection very rapidly. The half-lives of the two phases of decay are 0.7 days and 14 days. It is important to note that these decay processes occur continuously throughout untreated infection and are simply revealed when new infection events are blocked by ART. Thus, they are an essential feature of HIV-1 biology.

Surprisingly, the identity and fate of the cells that decay with these kinetics have never been clearly defined. Coincident with the initial studies of HIV-1 dynamics by Perelson and colleagues, studies from the Siliciano lab established that HIV-1 could persist in a latent form in resting CD4+ T cells, and it rapidly became clear that the half-life of this latent reservoir was extremely long (3.7 yrs), long enough to preclude cure even with optimal ART.

Using an SIV/Macaque model, Dr. Dan Barouch showed that this reservoir is established very early in infection. A fundamental hypothesis of this research program is that the latent reservoir is composed of cells that survive the rapid decay processes that eliminate the vast majority of infected cells. We believe that insights into reservoir dynamics can be obtained through analysis of these decay processes.

We will analyze these decay processes in coordinated studies in PLWH (Dr. Robert and Janet Siliciano, Project 1) and in SIV-infected macaques (Dr. Barouch, Project 2) with the help of Dr. Perelson and the Modeling Core.

The Johns Hopkins University

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]

Baltimore, Maryland 212051832 United States

Single Zip Code

Understanding HIV Reservoir Dynamics (P01, Clinical Trial Not Allowed) (RFA-AI-21-013)

Amendment Since initial award the total obligations have increased 294% from $1,604,953 to $6,324,187.