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

Hiv Clinical Trial

— DTG-SWITCH  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04612452
• Other study ID #: DTG-SWITCH Study protocol
• Status: Completed
• Start date: November 5, 2019
• Est. completion date: March 22, 2023

Study information

• Verified date: March 2023
• Source: University of Bern
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 2820
• Est. completion date: March 22, 2023
• Est. primary completion date: March 22, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

Patients

• On first-line ART for 6 months or longer

• Switching to any DTG-based treatment

Exclusion Criteria:

• No informed consent

Related Conditions & MeSH terms

• Drug Resistancy
• Hiv
• Virologic Failure

Locations

Country	Name	City	State
Malawi	Lighthouse Trust	Lilongwe
Zambia	CIDRZ	Lusaka

Sponsors (4)

Lead Sponsor	Collaborator
University of Bern	Centre for Infectious Disease Research in Zambia, Lighthouse Trust, University of KwaZulu

Countries where clinical trial is conducted

Malawi,  Zambia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The proportion of patients with VF at 48 weeks between patients with and without VF at baseline.		48 weeks
Secondary	The proportion of patients with VF at 96 weeks between patients with and without VF at baseline.		96 weeks
Secondary	The incidence of TLD drug resistances at 48 and 96 weeks in patients with and without VF at switch.		48 and 96 weeks
Secondary	The proportion of HIV-infected patients with VF at baseline.		Baseline
Secondary	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
Secondary	Prevalence of neuropsychiatric symptoms at baseline, 48 weeks and 96 weeks.		48 and 96 weeks
Secondary	Prevalence of insomnia at baseline, 48 weeks and 96 weeks.		48 and 96 weeks
Secondary	Weight change from baseline to 48 and 96 weeks.		48 and 96 weeks
Secondary	Levels of adherence at baseline and after 48 and 96 weeks.		48 and 96 weeks
Secondary	The number of clinical visits whilst on a DTG-based regimen up to 48 and 96 weeks.		48 and 96 weeks
Secondary	The number of clinical visits up to baseline, 48 and 96 weeks.		48 and 96 weeks