Evaluation of Switch to Dolutegravir/Lamivudine (DTG/3TC) From Current Suppressive Antiretroviral Therapy in People Living With HIV (PLWH) Receiving Opioid Agonist Therapy (OAT)

The goal of this clinical trial is to determine the efficacy of Dolutegravir/Lamivudine (DTG/3TC), or "Dovato", in virally-suppressed (HIV-1 RNA < 200 copies/mL) individuals receiving opioid agonist therapy such as methadone, buprenorphine, slow-release morphine, after switching from their current suppressive antiretroviral therapy (ART).

The main questions this trial seeks to answer are:

1. whether people living with HIV-1 (PLWH) on opioid agonist therapy (OAT) remain virally suppressed after switching to DTG/3TC from their current suppressive ART 48 weeks post-switch;
2. the number and type of adverse events (AEs) and serious adverse events (SAEs) attributable to DTG/3TC as documented per standard process at each study visit, and any discontinuations of DTG/3TC due to AEs and SAEs as determined by the study investigator;
3. the number of dosing changes in OAT attributable to DTG/3TC as determined by the study investigator and documented as per standard progress at each study visit;
4. the number of persons with any recreational or non-prescribed substances in their urine drug screens who remain virally suppressed (HIV-1 RNA < 200 copies/mL) at 48 weeks post-switch from current suppressive ART to DTG/3TC;
5. any change from baseline values (i.e., day 0) to 48 weeks post-switch from current suppressive ART to DTG/3TC of serum creatinine and non-fasting lipid parameters;
6. any change from baseline value (i.e., day 0) to 48 weeks post-switch from current suppressive ART to DTG/3TC in HIV Treatment Satisfaction Questionnaire (Status) (HIVTSQs) scores;
7. the number of persons who remain virally suppressed (HIV RNA < 200 copies/mL) at 48 weeks post-switch from current suppressive ART to DTG/3TC in conjunction with differing levels of adherence to DTG/3TC, and;
8. the number of persons who experience symptoms of opioid withdrawal or overdose per standardized survey or by self-report (e.g., overdose events)

During the course of the study, participants will complete:

• A set of questionnaires
• Blood draws
• A review of adverse events and concomitant medications
• ECG scans at screening and 48 weeks
• Urine drug screening
• Physical exams
• Review of alcohol consumption

Study Overview

• Status: Not yet recruiting
• Conditions: Opioid Use Disorder; HIV-1-infection
• Intervention / Treatment: Drug: DOVATO

Detailed Description

This study proposes to fill several important knowledge gaps regarding the safety and efficacy of switching to Dolutegravir/Lamivudine (DTG/3TC) in people living with HIV-1 (PLWH) on opioid agonist therapy (OAT) receiving care at the Infectious Diseases Clinic. As of this time, the Investigators are unaware of any real-world studies on the use of DTG/3TC in PLWH who are on OAT, PLWH using substances like fentanyl and crystal methamphetamine, or those of Indigenous ethnicity.

Additionally, clinical data on the use of DTG/3TC in young females is limited. The Infectious Diseases Clinic is well positioned to help further the understanding of real-world use of DTG/3TC among these understudied populations. With the inherent unpredictable adherence to current ART in PLWH receiving OAT, this study offers an opportunity to improve understanding of the real-world barrier to resistance of DTG/3TC in this clinical setting. The Principal Investigator proposes a single-arm, open-label, prospective interventional cohort study to evaluate the efficacy, and safety of switch to DTG/3TC from current suppressive ART in PLWH receiving OAT.

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Jones Kalyniuk, MSc; Phone Number: 306-766-4034; Email: jones.kalyniuk@saskhealthauthority.ca
• Study Contact Backup: Name: Sarah Craddock, HIM; Phone Number: 306-766-0576; Email: sarah.craddock@saskhealthauthority.ca

Study Locations

• Canada
  • Saskatchewan
    • Regina, Saskatchewan, Canada, S4P 0W5
      • Saskatchewan Health Authority
      • Principal Investigator: Alexander Wong, MD
      • Contact: Sarah Craddock, HIM; Phone Number: 306-766-0576; Email: sarah.craddock@saskhealthauthority.ca
      • Contact: Jones Kalyniuk, MSc.; Phone Number: 306-766-4034; Email: jones.kalyniuk@saskhealthauthority.ca
      • Sub-Investigator: Stephen Lee, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Male and females, 18 years or older
• HIV-1 infected
• Prescribed a combination antiretroviral therapy (cART) regimen that may include any Department of Health and Human Services (DHHS) recommended or alternative regimens, which the treating physician considers is appropriate for their patient, except Dolutegravir/Lamivudine (DTG/3TC), or with DTG and 3TC as separate components of a single ART regimen at any point previously
• HIV-1 RNA < 200 c/mL at screening and at least 3 months prior to screening
• CD4 ≥ 200 cells/mL at screening
• Prescribed opioid agonist therapy (OAT) with oral methadone, sublingual buprenorphine, subcutaneous buprenorphine, slow-release oral morphine, or any combination thereof for at least 3 months prior to screening and deemed stable on OAT by the investigator
• Ability to remain adherent to medications and study protocol as per investigator opinion
• Must be willing and able to understand the requirements of study participation and provide signed and dated written informed consent prior to screening

Exclusion Criteria:

• Co-infection with hepatitis B (HBsAg positive). Individuals who are negative for HBsAg and anti-HBs but positive for hepatitis B core antibody (anti-HBc) will be excluded if they have detectable HBV DNA (i.e. greater than 10 IU/mL).
• History or presence of allergy to any component of DTG/3TC
• Documented or suspected resistance to any component of DTG/3TC
• Tuberculosis infection requiring treatment
• Concomitant use of drugs with contraindication or unmanageable drug interactions with any component of DTG/3TC
• Alanine transferase (ALT) greater than 5 times the upper limit of normal (ULN), or ALT greater than 3 times the ULN and bilirubin greater than 1.5 times the ULN (with >35% direct bilirubin)
• Has an estimated glomerular filtration rate (eGFR; by MDRD equation) < 30 mL/min/1.73m2
• Severe hepatic impairment (Class C or greater) by Child-Pugh classification
• Is pregnant, planning to get pregnant, or lactating
• Involved in any other interventional HIV study during the study period
• Has any reason, in the opinion of the investigator, which would make the candidate inappropriate for participation in an investigative study involving oral medications

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment Arm; Switch to Dolutegravir/Lamivudine ("DOVATO") from current suppressive antiretroviral therapy in people living with HIV-1 receiving opioid agonist therapy.	Drug: DOVATO; HIV-1 medication; Other Names: Dolutegravir/Lamivudine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of people living with HIV-1 on opioid agonist therapy (OAT) that remain virally suppressed 48 weeks post-switch to Dolutegravir/Lamivudine (DTG/3TC)	The primary outcome assessed in the study is the number of individuals on OAT that remain virally suppressed (HIV RNA < 200 copies/mL) 48 weeks after switching from their current suppressive antiretroviral therapy (ART) to DTG/3TC.	Assessed at 48 weeks post-switch.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in dosing of DTG/3TC	Number and type of adverse events (AEs) and serious adverse events (SAEs) attributable to DTG/3TC as documented per standard process at each study visit, and any discontinuations of DTG/3TC due to AEs and SAEs as determined by the study investigator.	Through study completion, an average of 1 year.
Changes in dosing of OAT	Number of dosing changes in OAT attributable to DTG/3TC as determined by the study investigator and documented as per standard progress at each study visit.	Through study completion, an average of 1 year.
Evidence of recreational drug use while maintaining suppression	The number of persons with any recreational or non-prescribed substances in their urine drug screens who remain virally suppressed (HIV-1 RNA < 200 copies/mL) at 48 weeks post-switch from current suppressive ART to DTG/3TC.	Assessed at 48 weeks post-switch.
Changes in serum creatinine and non-fasting lipids	Change from baseline values (i.e., day 0) to 48 weeks post-switch from current suppressive ART to DTG/3TC of serum creatinine and non-fasting lipid parameters.	Assessed at 48 weeks post-switch.
Change in HIV-1 Treatment Satisfaction Questionnaire (status) (HIVTSQs) scores	Change from baseline value (i.e., day 0) to 48 weeks post-switch from current suppressive ART to DTG/3TC in HIVTSQs scores, ranging from 0 to 60, with 0 being the least satisfied with current HIV-1 treatment, and 60 being the most satisfied.	Assessed at 48 weeks post-switch.
Measurement of total adherence to DTG/3TC based on viral suppression	The number of persons who remain virally suppressed (HIV-1 RNA < 200 copies/mL) at 48 weeks post-switch from current suppressive ART to DTG/3TC in conjunction with differing levels of adherence to DTG/3TC.	Assessed at 48 weeks post-switch.
Assessment of withdrawal symptoms or overdose	The number of persons who experience symptoms of opioid withdrawal or overdose per standardized survey or by self-report (e.g., overdose events).	Through study completion, an average of 1 year.

Collaborators and Investigators

• Sponsor: Saskatchewan Health Authority - Regina Area
• Collaborators: ViiV Healthcare

Study record dates

Study Major Dates

• Study Start (Estimated): September 30, 2024
• Primary Completion (Estimated): May 31, 2026
• Study Completion (Estimated): October 31, 2027

Study Registration Dates

• First Submitted: August 28, 2024
• First Submitted That Met QC Criteria: August 29, 2024
• First Posted (Actual): August 30, 2024

Study Record Updates

• Last Update Posted (Actual): August 30, 2024
• Last Update Submitted That Met QC Criteria: August 29, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Keywords: Antiretroviral Therapy
• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders; Narcotic-Related Disorders; Opioid-Related Disorders; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; HIV Integrase Inhibitors; Integrase Inhibitors; Lamivudine; Dolutegravir
• Other Study ID Numbers: REB-24-04

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes