## Protocol Section
### Identification Module
**NCT ID:** NCT05333679

**Brief Title:** Urine Tenofovir Point-of-care Test to Identify Patients in Need of ART Adherence Support (UTRA Study)

**Official Title:** Urine Tenofovir Point-of-care Test to Identify Patients in Need of ART Adherence Support (UTRA Study)

#### Organization Study ID Info
**ID:** AI152119
#### Organization
**Class:** OTHER
**Full Name:** University of California, San Francisco
### Status Module
#### Completion Date
**Date:** 2025-06-30

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2023-06-08

**Type:** ACTUAL

**Last Update Submit Date:** 2023-06-07

**Overall Status:** RECRUITING

#### Primary Completion Date
**Date:** 2024-03-01

**Type:** ESTIMATED

#### Start Date
**Date:** 2022-03-02

**Type:** ACTUAL

**Status Verified Date:** 2023-06

#### Study First Post Date
**Date:** 2022-04-19
**Type:** ACTUAL
**Study First Submit Date:** 2022-04-11
**Study First Submit QC Date:** 2022-04-11
### Sponsor Collaborators Module

#### Collaborators

**Class:** OTHER

**Name:** University of Cape Town

**Class:** OTHER

**Name:** University of Stellenbosch

#### Lead Sponsor

**Class:** OTHER

**Name:** University of California, San Francisco

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Is FDA Regulated Device:** True

**Is FDA Regulated Drug:** False

**Is US Export:** True

**Oversight Has DMC:** False

### Description Module

**Brief Summary:** ART is given to people living with HIV in order to suppress the virus, resulting in improved health for the individual and decreased transmission of the virus to others. Success of ART is dependent on adherence. Currently, adherence is assessed by asking patients directly and then confirming with a viral load test, which is expensive and is often only done when the viral load is already raised. Therefore there is a need to find a method to detect problems with adherence early before the viral load rises.

A urine-based test was recently developed, called UTRA (urine tenofovir rapid assay). This test can give clinic staff immediate results about a person's adherence to the antiretroviral medication Tenofovir (TDF). The study will compare the results of this urine test to drug levels found in blood, self-reported adherence and pharmacy collection records to see if this test can be used as part of routine care in ART clinics. If the test is effective it would allow clinic staff to identify people with adherence difficulties early and give them the necessary support before their viral load rises.

**Detailed Description:** This is a randomised study, recruiting 200 people taking TDF-based ART. Participants will be randomised 1:1 to intervention versus standard enhanced adherence counselling. Intervention participants will receive an adherence support package informed by feedback from the urine-based test. The investigators will assess the impact of the adherence test on VL suppression rates in each arm (without necessitating a regimen switch) at 12 months after enrolment. Enrolling participants with adherence challenges increases efficiency and mirrors the population requiring adherence support in our setting.

The UTRA device used for this study has received a FDA Non-Significant Risk (NSR) designation and is IDE exempt.

FEASIBILITY:

The investigators will track retention in the study among participants in each arm, missed visits, and the number of urine assessments performed in the intervention arm.

ACCEPTABILITY:

All participants enrolled will also complete a standardised questionnaire about the acceptability of the adherence support they received. This measure of acceptability will be assessed as a secondary outcome by arm, along with socio-demographics profiles associated with low/high acceptability described within arm.

QUALITATIVE PROCEDURES:

1. Participant in-depth interviews: Qualitative data will include in-depth interviews of participants (n\~20; \~3-4 interviews with each participant over 6-9 months of their treatment) using semi-structured guides conducted by experienced socio-behavioural scientists. The semi-structured interview guide will elicit feelings about the urine adherence metric and counseling messages, concerns regarding privacy, advantages/disadvantages of receiving such results, and the likely impact of this monitoring test on sustained adherence to ART or just on short-term adherence. Interviews will be conducted in participants' preferred language.
2. Health care worker interviews: The investigators will additionally assess the feasibility of the intervention by interviewing health care providers, who will be administering the UTRA test at the clinical point of care in the future. The study will examine provider perceptions of the assay at the end of the study using in-depth interviews (n\~10), assessing perceived usefulness, complexity to use, stigma/social harm, and benefits. These interviews will also elicit barriers and facilitators to delivery of the urine assay-informed counseling messages.

### Conditions Module

**Conditions:**

- Risk Reduction

**Keywords:**

- UTRA

- Point-of-care

- Real-time

- PLHIV

- Adherence monitoring

- ART

### Design Module

#### Design Info

**Allocation:** RANDOMIZED

**Intervention Model:** PARALLEL

##### Masking Info

**Masking:** NONE

**Primary Purpose:** PREVENTION

#### Enrollment Info

**Count:** 200

**Type:** ESTIMATED

**Phases:**

- NA

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** POC adherence testing by a urine TFV assay with feedback

**Intervention Names:**

- Device: UTRA

- Behavioral: UTRA feedback

**Label:** Intervention

**Type:** EXPERIMENTAL

#### Arm Group 2

**Description:** Standard enhanced adherence counselling, SA Department of Health, March 2020

**Label:** Standard of Care

**Type:** NO_INTERVENTION

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Intervention

**Description:** Collect urine on intervention participants and screen for presence of TFV.

**Name:** UTRA

**Type:** DEVICE

#### Intervention 2

**Arm Group Labels:**

- Intervention

**Description:** Feedback will be provided to the participant based on the UTRA results on their adherence with provision of standard adherence counseling.

**Name:** UTRA feedback

**Type:** BEHAVIORAL

### Outcomes Module

#### Primary Outcomes

**Description:** Assess suppression rates (VL\< 50 copies/mL) in both study arms using an intention-to-treat analysis. Plasma will be stored an enrolment, month 6 and month 12 for viral load assay completion after the study. Samples are assayed either with the Alinity m HIV-1 assay (Abbott Laboratories. Abbott Park, Illinois, U.S.A.); lower limit of detection (LLD) 10 copies/mL or the COBAS® AmpliPrep/COBAS® TaqMan® HIV-1 Test, v2.0 (Roche Diagnostics, Basel, Switzerland); LLD 20 copies/mL. Whole blood will be centrifuged and plasma then tested on the automated analyzer according to national standard operating procedures

**Measure:** Proportion of participants in each arm achieving viral suppression to <50 copies/ml

**Time Frame:** 12 months

#### Secondary Outcomes

**Description:** Follow up visits will occur in 12-week increments post-enrolment: at month 3, month 6, month 9 and month 12; and will be synchronized wherever possible with routine clinic visits. Visit windows will be continuous, with each window extending to 6 weeks before and 6 weeks after the visit target date. A visit will be considered missed if the participant does not attend during the 12-week visit window

**Measure:** Retention in care

**Time Frame:** 12 months

**Description:** Assess suppression rates (VL\< 50 copies/mL) in both study arms using an intention-to-treat analysis. Samples are assayed either with the Alinity m HIV-1 assay (Abbott Laboratories. Abbott Park, Illinois, U.S.A.); lower limit of detection (LLD) 10 copies/mL or the COBAS® AmpliPrep/COBAS® TaqMan® HIV-1 Test, v2.0 (Roche Diagnostics, Basel, Switzerland); LLD 20 copies/mL. Whole blood will be centrifuged and plasma then tested on the automated analyzer according to national standard operating procedures

**Measure:** Viral suppression (<50 copies/mL)

**Time Frame:** 6 months

**Description:** The proportion of participants indicating "strongly agree" or "agree" averaged across 10 items, each item using a five-point Likert scale to measure aspects of acceptability of the adherence support intervention (i.e., by arm: UTRA-informed or standard of care), at month 12. Responses to the Likert scale range from "Strongly agree" to "Strongly disagree". Aspects of acceptability include domains on: support from health workers, time given by health workers to discuss the patients' treatment, patient perceptions of feeling informed about their adherence, feelings of surveillance (-vely scored), and self-satisfactions with adherence.

**Measure:** The proportion of participants indicating "strongly agree" or "agree" averaged across 10 items, each using a five-point Likert scale to measure aspects of the adherence support intervention (i.e., by arm: UTRA-informed or standard of care)

**Time Frame:** 12 months

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

* ≥18 years old
* Willing and able to provide written informed consent
* HIV-infected, receiving or (re-)starting a tenofovir-based ART regimen
* Current ART regimen includes at least one drug with a high genetic barrier to resistance e.g. dolutegravir, atazanavir/ritonavir, darunavir/ritonavir or lopinavir/ritonavir.
* Any previous raised viral load \>50 copies/ml (after ART initiation).
* Willing and able to comply with laboratory tests and other study procedures

Exclusion Criteria:

* Not willing or able to provide informed consent in any of the languages provided
* Not receiving a tenofovir-based ART regimen
* Any other clinical condition that in the opinion of an investigator puts the patient at increased risk if participating in the study.

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** Monica.Gandhi@ucsf.edu

**Name:** Monica Gandhi, MD

**Phone:** 415 476 4082

**Phone Ext:** 127

**Role:** CONTACT

**Contact 2:**

**Email:** Purba.Chatterjee@ucsf.edu

**Name:** Purba Chatterjee, MSc

**Phone:** 415 476 6714

**Role:** CONTACT

#### Locations

**Location 1:**

**City:** Cape Town

**Contacts:**

***Contact 1:***

- **Email:** Catherine.orrell@hiv-research.org.za

- **Name:** Catherine Orrell, MBChB, PhD

- **Phone:** (021) 406 6958

- **Role:** CONTACT

***Contact 2:***

- **Email:** Zukiswa.Nkantsu@hiv-research.org.za

- **Name:** Zukiswa Nkantsu

- **Phone:** (021) 007 2275/6

- **Role:** CONTACT

***Contact 3:***

- **Name:** Catherine Orrell, MBChB, PhD

- **Role:** PRINCIPAL_INVESTIGATOR

***Contact 4:***

- **Name:** Yashna Singh, MBBS

- **Role:** SUB_INVESTIGATOR

***Contact 5:***

- **Name:** Lauren Jennings, MBChB

- **Role:** SUB_INVESTIGATOR

**Country:** South Africa

**Facility:** Desmond Tutu Health Foundation, University of Cape Town

**State:** Western Cape

**Status:** RECRUITING

**Zip:** 7925

#### Overall Officials

**Official 1:**

**Affiliation:** University of California, San Francisco

**Name:** Monica Gandhi, MD

**Role:** PRINCIPAL_INVESTIGATOR

### IPD Sharing Statement Module

**Access Criteria:** Investigators conducting PrEP research

**Description:** We will share de-identified data in publicly accessible databases once study is complete and study findings disseminated.

**Info Types:**

- STUDY_PROTOCOL

- SAP

- ICF

- CSR

- ANALYTIC_CODE

**IPD Sharing:** YES

**Time Frame:** 48 months from start of study

### References Module

#### References

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**PMID:** 21507924

**Citation:** Cohan D, Natureeba P, Koss CA, Plenty A, Luwedde F, Mwesigwa J, Ades V, Charlebois ED, Gandhi M, Clark TD, Nzarubara B, Achan J, Ruel T, Kamya MR, Havlir DV. Efficacy and safety of lopinavir/ritonavir versus efavirenz-based antiretroviral therapy in HIV-infected pregnant Ugandan women. AIDS. 2015 Jan 14;29(2):183-91. doi: 10.1097/QAD.0000000000000531.

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**Citation:** Koss CA, Natureeba P, Mwesigwa J, Cohan D, Nzarubara B, Bacchetti P, Horng H, Clark TD, Plenty A, Ruel TD, Achan J, Charlebois ED, Kamya MR, Havlir DV, Gandhi M. Hair concentrations of antiretrovirals predict viral suppression in HIV-infected pregnant and breastfeeding Ugandan women. AIDS. 2015 Apr 24;29(7):825-30. doi: 10.1097/QAD.0000000000000619. Erratum In: AIDS. 2015 Nov;29(17):2369.

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**PMID:** 30037297

**Citation:** Keene CM, Griesel R, Zhao Y, Gcwabe Z, Sayed K, Hill A, Cassidy T, Ngwenya O, Jackson A, van Zyl G, Schutz C, Goliath R, Flowers T, Goemaere E, Wiesner L, Simmons B, Maartens G, Meintjes G. Virologic efficacy of tenofovir, lamivudine and dolutegravir as second-line antiretroviral therapy in adults failing a tenofovir-based first-line regimen. AIDS. 2021 Jul 15;35(9):1423-1432. doi: 10.1097/QAD.0000000000002936.

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**PMID:** 28705153

**Citation:** Koenig HC, Mounzer K, Daughtridge GW, Sloan CE, Lalley-Chareczko L, Moorthy GS, Conyngham SC, Zuppa AF, Montaner LJ, Tebas P. Urine assay for tenofovir to monitor adherence in real time to tenofovir disoproxil fumarate/emtricitabine as pre-exposure prophylaxis. HIV Med. 2017 Jul;18(6):412-418. doi: 10.1111/hiv.12518. Epub 2017 Apr 26.

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**PMID:** 27338974

**Citation:** Spinelli MA, Glidden DV, Rodrigues WC, Wang G, Vincent M, Okochi H, Kuncze K, Mehrotra M, Defechereux P, Buchbinder SP, Grant RM, Gandhi M. Low tenofovir level in urine by a novel immunoassay is associated with seroconversion in a preexposure prophylaxis demonstration project. AIDS. 2019 Apr 1;33(5):867-872. doi: 10.1097/QAD.0000000000002135.

**PMID:** 30649051

**Citation:** Parienti JJ, Das-Douglas M, Massari V, Guzman D, Deeks SG, Verdon R, Bangsberg DR. Not all missed doses are the same: sustained NNRTI treatment interruptions predict HIV rebound at low-to-moderate adherence levels. PLoS One. 2008 Jul 30;3(7):e2783. doi: 10.1371/journal.pone.0002783.

**PMID:** 18665246

**Citation:** Parienti JJ, Ragland K, Lucht F, de la Blanchardiere A, Dargere S, Yazdanpanah Y, Dutheil JJ, Perre P, Verdon R, Bangsberg DR; ESPOIR and REACH study groups. Average adherence to boosted protease inhibitor therapy, rather than the pattern of missed doses, as a predictor of HIV RNA replication. Clin Infect Dis. 2010 Apr 15;50(8):1192-7. doi: 10.1086/651419.

**PMID:** 20210643

**Citation:** Gandhi M, Glidden DV, Liu A, Anderson PL, Horng H, Defechereux P, Guanira JV, Grinsztejn B, Chariyalertsak S, Bekker LG, Grant RM; iPrEx Study Team. Strong Correlation Between Concentrations of Tenofovir (TFV) Emtricitabine (FTC) in Hair and TFV Diphosphate and FTC Triphosphate in Dried Blood Spots in the iPrEx Open Label Extension: Implications for Pre-exposure Prophylaxis Adherence Monitoring. J Infect Dis. 2015 Nov 1;212(9):1402-6. doi: 10.1093/infdis/jiv239. Epub 2015 Apr 20.

**PMID:** 25895984

**Citation:** Gandhi M, Murnane PM, Bacchetti P, Elion R, Kolber MA, Cohen SE, Horng H, Louie A, Kuncze K, Koss CA, Anderson PL, Buchbinder S, Liu A. Hair levels of preexposure prophylaxis drugs measure adherence and are associated with renal decline among men/transwomen. AIDS. 2017 Oct 23;31(16):2245-2251. doi: 10.1097/QAD.0000000000001615.

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**Citation:** Koss CA, Hosek SG, Bacchetti P, Anderson PL, Liu AY, Horng H, Benet LZ, Kuncze K, Louie A, Saberi P, Wilson CM, Gandhi M. Comparison of Measures of Adherence to Human Immunodeficiency Virus Preexposure Prophylaxis Among Adolescent and Young Men Who Have Sex With Men in the United States. Clin Infect Dis. 2018 Jan 6;66(2):213-219. doi: 10.1093/cid/cix755.

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