Clinical trial NCT04612452: The DTG-SWITCH Study: Longitudinal Analysis of Virologic Failure and Drug Resistance at and After Switching to Dolutegravir-based First-line ART
Official title: The DTG-SWITCH Study: Longitudinal Analysis of Virologic Failure and Drug Resistance at and After Switching to Dolutegravir-based First-line ART
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Hiv
Drug Resistancy
Virologic Failure
Keywords: Hiv
Drug resistancy
Virologic failure
DTG-based regimen
Drug resistance mutations
Lead sponsor: University of Bern
Sponsor class: OTHER
Collaborators: name: University of KwaZulu
name: Lighthouse Trust
name: Centre for Infectious Disease Research in Zambia
First posted: 2020-11-03
Enrollment: 2820
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: People living with HIV.

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.

Eligibility criteria: Inclusion Criteria:

Patients

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

Exclusion Criteria:

* No informed consent

Primary outcomes:
measure: The proportion of patients with VF at 48 weeks between patients with and without VF at baseline.
timeFrame: 48 weeks
Secondary outcomes:
measure: The proportion of patients with VF at 96 weeks between patients with and without VF at baseline.
timeFrame: 96 weeks
measure: The incidence of TLD drug resistances at 48 and 96 weeks in patients with and without VF at switch.
timeFrame: 48 and 96 weeks
measure: The proportion of HIV-infected patients with VF at baseline.
timeFrame: Baseline
measure: 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.
timeFrame: 48 and 96 weeks
measure: Prevalence of neuropsychiatric symptoms at baseline, 48 weeks and 96 weeks.
timeFrame: 48 and 96 weeks
measure: Prevalence of insomnia at baseline, 48 weeks and 96 weeks.
timeFrame: 48 and 96 weeks
measure: Weight change from baseline to 48 and 96 weeks.
timeFrame: 48 and 96 weeks
measure: Levels of adherence at baseline and after 48 and 96 weeks.
timeFrame: 48 and 96 weeks
measure: The number of clinical visits whilst on a DTG-based regimen up to 48 and 96 weeks.
timeFrame: 48 and 96 weeks
measure: The number of clinical visits up to baseline, 48 and 96 weeks.
timeFrame: 48 and 96 weeks
Other outcomes:
Locations:
city: Lilongwe
country: Malawi
facility: Lighthouse Trust
city: Lusaka
country: Zambia
facility: CIDRZ
Study officials:
affiliation: University of Berne
name: Matthias Egger, Prof.
role: STUDY_DIRECTOR
References: