TRIAGING DOLUTEGRAVIR RESISTANCE VIA A POINT-OF-CARE URINE TENOFOVIR ASSAY - PROJECT SUMMARY/ ABSTRACT TENO…

Assistance award details

Assistance award identifier

ASST_NON_R01AI191753_075

FAIN

R01AI191753

Recipient

REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE

Awarding agency

Department of Health and Human Services

Funding agency

Department of Health and Human Services

Assistance listing (CFDA)

93.855

Total obligated

$1,406,742

Period

Sep 15, 2025 – Aug 31, 2030

Fiscal year

2025

Place of performance state

CA

Source file

FY2025_All_Assistance_Full_20261006.zip

Description

TRIAGING DOLUTEGRAVIR RESISTANCE VIA A POINT-OF-CARE URINE TENOFOVIR ASSAY - PROJECT SUMMARY/ ABSTRACT TENOFOVIR (TFV)-LAMIVUDINE-DOLUTEGRAVIR (TLD) HAS BEEN FIRST LINE HIV THERAPY WORLDWIDE SINCE 2018. TLD IS ALSO USED AS SECOND LINE THERAPY MORE RECENTLY IN THOSE WITH A HISTORY OF PRIOR TREATMENT EXPERIENCE. HOWEVER, IN 2024, THERE IS EVIDENCE OF INCREASING RATES OF DOLUTEGRAVIR (DTG) RESISTANCE GLOBALLY (4-8%), WITH RATES UP TO 20% AMONG THOSE WITH VIROLOGIC FAILURE AND TREATMENT EXPERIENCE. INTEGRASE STRAND TRANSFERASE INHIBITOR (INSTI) RESISTANCE SCREENING WORLDWIDE IS THEREFORE AN URGENT GLOBAL PRIORITY, ALTHOUGH HIV DRUG RESISTANCE (HIVDR) IS STILL SEVERELY RATIONED IN MOST LOW-AND-MIDDLE-INCOME COUNTRIES DUE TO COST. HIVDR IS HIGHER AMONG PEOPLE LIVING WITH HIV (PWH) WITH VIROLOGIC FAILURE AND LABORATORY-CONFIRMED EXPOSURE TO ART, DEMONSTRATING THAT HIGH VIRAL LOADS COMBINED WITH ART EXPOSURE ARE MORE LIKELY TO SIGNAL HIV DRUG RESISTANCE (HIVDR) DUE TO SELECTIVE DRUG PRESSURE FROM THE ANTIRETROVIRAL(S) ON THE VIRUS TO EVOLVE. THE 2023 SOUTH AFRICA TREATMENT GUIDELINES NOW STATE HIVDR TESTING SHOULD ONLY BE REQUESTED AFTER 2 ELEVATED VIRAL LOADS ON TLD ARE DOCUMENTED AND ADHERENCE IS ESTABLISHED USING ONE OF FIVE OBJECTIVE ADHERENCE METRICS; 1) A URINE ASSAY TO DETECT TENOFOVIR (TFV); 2) DTG LEVELS IN PLASMA; 3) TENOFOVIR-DIPHOSPHATE (TFV-DP) LEVELS IN DRIED BLOOD SPOTS (DBS); 4) CLINIC ATTENDANCE; 4) PHARMACY REFILL DATA. OUR LABORATORY GROUP AT UCSF RECENTLY DEVELOPED A POINT-OF-CARE URINE TFV ASSAY THAT CAN ASSESS WITH HIGH ACCURACY WHETHER TFV WAS RECENTLY INGESTED. HOWEVER, THE URINE ASSAY HAS NOT BEEN RIGOROUSLY STUDIED FOR THE PREDICTION OF RESISTANCE IN PWH FAILING TLD TO DATE. WE THEREBY PROPOSE TO TEST THE ABILITY OF THE URINE TFV ASSAY TO TRIAGE HIV DRUG RESISTANCE TESTING IN SOUTH AFRICA, COMPARING IT TO OTHER METRICS AND ASSESSING COST. WE WILL FIRST COMPARE THE PREVALENCE OF DTG RESISTANCE AMONG PWH WITH PRIOR TREATMENT EXPERIENCE FAILING TLD