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

Completed

• Conditions: Virologic Failure; Hiv; Drug Resistancy

• Registration Number: NCT04612452
• Lead Sponsor: University of Bern

Brief Summary

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.

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 Timeline

• Study Start: 2019-11-05
• Study First Submitted: 2020-10-27
• Study First Submitted QC: 2020-10-27
• Study First Posted: 2020-11-03
• Status Verified: 2023-03
• Primary Completion: 2023-03-22
• Study Completion: 2023-03-22
• Last Update Submitted: 2023-03-23
• Last Update Posted: 2023-03-24

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 2820

Inclusion Criteria

Patients

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

Exclusion Criteria

• No informed consent

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
The proportion of patients with VF at 48 weeks between patients with and without VF at baseline.	48 weeks

Secondary Outcome Measures

Name	Time	Method
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
Levels of adherence at baseline and after 48 and 96 weeks.	48 and 96 weeks
Prevalence of neuropsychiatric symptoms at baseline, 48 weeks and 96 weeks.	48 and 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 number of clinical visits whilst on a DTG-based regimen up to 48 and 96 weeks.	48 and 96 weeks
The proportion of patients with VF at 96 weeks between patients with and without VF at baseline.	96 weeks
The number of clinical visits up to baseline, 48 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

Trial Locations

Locations (2)

Lighthouse Trust; 🇲🇼 Lilongwe, Malawi

CIDRZ; 🇿🇲 Lusaka, Zambia