Official websites use .gov

A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS

A lock ( 🔒 ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Need Help

Delineating the viro-immunological factors contributing to transient HIV control during consecutive analytical treatment interruptions

Award Number: R21AI183975
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/18/2024
PERIOD OF PERFORMANCE END DATE: 05/31/2026

Group Awards By:

View Award Description

Delineating the viro-immunological factors contributing to transient HIV control during consecutive analytical treatment interruptions - Project Summary During effective antiretroviral therapy (ART), human immunodeficiency virus (HIV) persists in memory T cells and the virus from this cellular reservoir rebounds when people living with HIV (PLWH) stop ART. When ART is discontinued, viral rebound takes place within 4 weeks in most PLWH (i.e., non-controllers). However, the time to viral rebound varies and there are rare PLWH who maintain low levels of viremia for months or years after an analytic treatment interruption (ATI). Previous studies have identified several factors associated with a delayed time to viral rebound: 1) lower levels of total HIV DNA prior to treatment interruption; 2) lower pre-ART viral load; and 3) initiation of ART during acute/early infection. In addition, CD8 T cell immune response directed against structurally important viral protein regions is also associated with viral control in the absence of ART. From the results of the PULSE clinical trial, where 68 PLWHs underwent three consecutive ATIs, we observed that 10% of the participants controlled their viral rebound up to 6 months (i.e., transient controllers). Applying our novel near full-length HIV RNA sequencing assay to genetically characterize HIV from the plasma of two participants enrolled in this clinical study, we found that genetically distinct HIV populations emerged when transient viral control was observed. In the current study, we will extend our full-length HIV sequencing analysis to all participants who experienced transient viral control during consecutive ATIs. In addition, to determine whether enhanced CD8 T cell response and functionality are essential to achieve transient viral control during consecutive ATIs, we will compare the proportion of HIV-specific CD8 T cells and the magnitude of their response across pre-ART and ATI timepoints in both transient controllers and non-controllers. Furthermore, we will determine whether consecutive ATIs improve HIV-specific CD8 T cell response to structurally important and genetically conserved viral protein regions shaping the genetic composition of rebound viruses and controlling viral infection. The proposed study will allow us to determine if consecutive ATIs enhance viral and immunological mechanisms contributing to transient viral control. Of note, we will define the immunological parameters of CD8 T cells that result in a transient virological control and delayed viral rebound when ART is discontinued. Moreover, this study will accelerate the development of new therapeutic strategies such as enhancing host immunity against structurally important and genetically conserved HIV protein regions with the ultimate goal of achieving virological remission following the discontinuation of ART.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $174,318 )
2025	2025	UNIVERSITY OF SYDNEY	RESEARCH OFFICE MAIN QUADRANGLE A14	THE UNIVERSITY OF SYDNEY				AUS	Allergy and Infectious Diseases Research	000	2	6/25/2025	NON-COMPETING CONTINUATION	$174,318
														Subtotal = $174,318

Issue Date FY: 2024 ( Subtotal = $110,414 )
2024	2024	UNIVERSITY OF SYDNEY	RESEARCH OFFICE MAIN QUADRANGLE A14	THE UNIVERSITY OF SYDNEY				AUS	Allergy and Infectious Diseases Research	000	1	7/18/2024	NEW	$110,414
														Subtotal = $110,414

Grand Total All Awards = $284,732

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Delineating the viro-immunological factors contributing to transient HIV control during consecutive analytical treatment interruptions

Award Number: R21AI183975

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 07/18/2024

PERIOD OF PERFORMANCE END DATE: 05/31/2026

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer