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

• ClinicalTrials.gov Identifier: NCT04612452
• Recruitment Status: Active, not recruiting
• First Posted: November 3, 2020
• Last Update Posted: March 3, 2022
• Sponsor: University of Bern
• Collaborators: University of KwaZulu; Lighthouse Trust; Centre for Infectious Disease Research in Zambia
• Information provided by (Responsible Party): University of Bern

Study Description

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.

Condition or disease
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 Design

• Study Type: Observational
• Estimated Enrollment: 2820 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: The DTG-SWITCH Study: Longitudinal Analysis of Virologic Failure and Drug Resistance at and After Switching to Dolutegravir-based First-line ART
• Actual Study Start Date: November 5, 2019
• Actual Primary Completion Date: November 30, 2021
• Estimated Study Completion Date: November 30, 2022

Groups and Cohorts

Group/Cohort
Lighthouse Trust in Lilongwe
CIDRZ in Lusaka

Outcome Measures

Primary Outcome Measures :

1. The proportion of patients with VF at 48 weeks between patients with and without VF at baseline. [ Time Frame: 48 weeks ]

Secondary Outcome Measures :

1. The proportion of patients with VF at 96 weeks between patients with and without VF at baseline. [ Time Frame: 96 weeks ]
2. The incidence of TLD drug resistances at 48 and 96 weeks in patients with and without VF at switch. [ Time Frame: 48 and 96 weeks ]
3. The proportion of HIV-infected patients with VF at baseline. [ Time Frame: Baseline ]
4. 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. [ Time Frame: 48 and 96 weeks ]
5. Prevalence of neuropsychiatric symptoms at baseline, 48 weeks and 96 weeks. [ Time Frame: 48 and 96 weeks ]
6. Prevalence of insomnia at baseline, 48 weeks and 96 weeks. [ Time Frame: 48 and 96 weeks ]
7. Weight change from baseline to 48 and 96 weeks. [ Time Frame: 48 and 96 weeks ]
8. Levels of adherence at baseline and after 48 and 96 weeks. [ Time Frame: 48 and 96 weeks ]
9. The number of clinical visits whilst on a DTG-based regimen up to 48 and 96 weeks. [ Time Frame: 48 and 96 weeks ]
10. The number of clinical visits up to baseline, 48 and 96 weeks. [ Time Frame: 48 and 96 weeks ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• Sampling Method: Non-Probability Sample

Study Population

People living with HIV.

Criteria

Inclusion Criteria:

Patients

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

Exclusion Criteria:

• No informed consent

Contacts and Locations

Locations

Malawi

Lighthouse Trust

Lilongwe, Malawi

Zambia

CIDRZ

Lusaka, Zambia

Sponsors and Collaborators

University of Bern

University of KwaZulu

Lighthouse Trust

Centre for Infectious Disease Research in Zambia

Investigators

• Study Director: Matthias Egger; University of Berne

More Information

• Responsible Party: University of Bern
• ClinicalTrials.gov Identifier: NCT04612452
• Other Study ID Numbers: DTG-SWITCH Study protocol
• First Posted: November 3, 2020
• Last Update Posted: March 3, 2022
• Last Verified: February 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• 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

Keywords provided by University of Bern:

Hiv; Drug resistancy; Virologic failure; DTG-based regimen; Drug resistance mutations