The DTG-SWITCH Study: Longitudinal Analysis of Virologic Failure and Drug Resistance at and After Switching to Dolutegravir-based First-line ART (DTG-SWITCH)

This is a prospective observational cohort study of 2820 patients on first-line ART switching to a DTG-based first-line regimen, according to the standard of care. The study is conducted in Malawi and Zambia, in ART programs that participate in the IeDEA collaboration. Sequencing will be done on blood samples of patients with a viral load above 400 copies/mL to identify mutations.

Study Overview

• Status: Completed
• Conditions: Hiv; Drug Resistancy; Virologic Failure

Detailed Description

Dolutegravir (DTG), a second-generation integrase strand transfer inhibitor (InSTI), is widely used in high-income countries and is recommended by the World Health Organization (WHO) as an alternative first-line ART regimen. In countries where viral load monitoring is not routinely available many patients on first-line ART will be switched to a DTG-based regimen despite the detectable viral load, which could increase the risk of selection of resistance to DTG as the majority of patients with virologic failure on first-line EFV-based ART have NRTI mutations. The investigators hypothesize that the proportion of patients experiencing virologic failure 48 and 96 weeks after switching to a DTG-based regimen will be higher in patients who switched with virologic failure (VL>400 copies/mL) compared to patients who switched with suppressed viral replication (VL<400 copies/mL). This is a prospective observational cohort study of 2820 patients on first-line ART switching to a DTG-based first-line regimen, according to the standard of care. The study is conducted in Malawi and Zambia, in ART programs that participate in the IeDEA collaboration. At the time of switching to DTG, a baseline study assessment will be done, and a blood sample will be taken. Sequencing will be done on blood samples of patients with a viral load above 400 copies/mL to identify mutations.

• Study Type: Observational
• Enrollment (Actual): 2820

Contacts and Locations

Study Locations

• Malawi
  • Lilongwe, Malawi
    • Lighthouse Trust
• Zambia
  • Lusaka, Zambia
    • CIDRZ

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

People living with HIV.

Description

Inclusion Criteria:

Patients

• On first-line ART for 6 months or longer
• Switching to any DTG-based treatment

Exclusion Criteria:

• No informed consent

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Lighthouse Trust in Lilongwe
CIDRZ in Lusaka

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The proportion of patients with VF at 48 weeks between patients with and without VF at baseline.	48 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
The proportion of patients with VF at 96 weeks between patients with and without VF at baseline.	96 weeks
The incidence of TLD drug resistances at 48 and 96 weeks in patients with and without VF at switch.	48 and 96 weeks
The proportion of HIV-infected patients with VF at baseline.	Baseline
The proportion of patients with VF at 48 weeks and 96 weeks in patients with VF at baseline who have at least one or no fully active NRTI on resistance testing.	48 and 96 weeks
Prevalence of neuropsychiatric symptoms at baseline, 48 weeks and 96 weeks.	48 and 96 weeks
Prevalence of insomnia at baseline, 48 weeks and 96 weeks.	48 and 96 weeks
Weight change from baseline to 48 and 96 weeks.	48 and 96 weeks
Levels of adherence at baseline and after 48 and 96 weeks.	48 and 96 weeks
The number of clinical visits whilst on a DTG-based regimen up to 48 and 96 weeks.	48 and 96 weeks
The number of clinical visits up to baseline, 48 and 96 weeks.	48 and 96 weeks

Collaborators and Investigators

• Sponsor: University of Bern
• Collaborators: Centre for Infectious Disease Research in Zambia; Lighthouse Trust; University of KwaZulu
• Investigators: Study Director: Matthias Egger, Prof., University of Berne

Study record dates

Study Major Dates

• Study Start (Actual): November 5, 2019
• Primary Completion (Actual): March 22, 2023
• Study Completion (Actual): March 22, 2023

Study Registration Dates

• First Submitted: October 27, 2020
• First Submitted That Met QC Criteria: October 27, 2020
• First Posted (Actual): November 3, 2020

Study Record Updates

• Last Update Posted (Actual): March 24, 2023
• Last Update Submitted That Met QC Criteria: March 23, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: Hiv; Drug resistancy; Virologic failure; DTG-based regimen; Drug resistance mutations
• Other Study ID Numbers: DTG-SWITCH Study protocol

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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