Ignite Creation Date:
2024-05-06 @ 8:12 PM
Last Modification Date:
2024-10-26 @ 3:22 PM
Study NCT ID:
NCT06285110
Status:
RECRUITING
Last Update Posted:
2024-02-29
First Post:
2023-05-08
Brief Title:
HIV-1 Subtype-specific Drug Resistance in Patients Failing Dolutegravir DTG Based Regimen
Sponsor:
University of Bern
Organization:
University of Bern
Study Overview
Official Title:
HIV-1 Subtype-specific Drug Resistance in Patients Failing Dolutegravir-based 1st 2nd or 3rd Line Regimens the International Epidemiological Databases to Evaluate AIDS IeDEA
Status:
RECRUITING
Status Verified Date:
2024-02
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
DTG-Resist
Brief Summary:
This is a prospective observational study enrolling People Living with HIV PLHIV who are on a Dolutegravir-based AntiRetroviral Treatment ART regimen and experiencing virologic failure Virologic failure is defined as two consecutive viral load measurements of 1000 copiesmL of blood The main aim of the study is to identify the drug-resistance mutations in the viral genome that are associated with this failure
To achieve this goal patients fulfilling the eligibility criteria will be invited for a single study visit for the collection of blood The extracted HIV virus will be sequenced through whole genome sequencing methods to identify the drug-resistance mutations The study is conducted in 15-20 countries within six regions of the IeDEA cohort International epidemiology Databases to Evaluate AIDS
To achieve this goal patients fulfilling the eligibility criteria will be invited for a single study visit for the collection of blood The extracted HIV virus will be sequenced through whole genome sequencing methods to identify the drug-resistance mutations The study is conducted in 15-20 countries within six regions of the IeDEA cohort International epidemiology Databases to Evaluate AIDS
Detailed Description:
With the expansion of access to Anti-Retroviral Treatment ART in Low and Middle-Income Countries LMIC there is an increase in HIV drug resistance The previously recommended 1st-line regimen of Tenofovir Emtricitabine and Efavirenz TEE contains three drugs with a low genetic barrier to resistance As a result acquired drug resistance mutations are detected in the majority of people on TEE across different regions and HIV-1 subtypes There has also been a steady increase in Pre-treatment Drug Resistance PDR as ART coverage has expanded in LMIC WHO now recommends the use of Dolutegravir DTG in 1st - 2nd and 3rd-line ART for adults and adolescents Therefore in most countries PLHIV are transitioned to a DTG-based regimen DTG is a potent Integrase Strand Transfer Inhibitor InSTI which has better efficacy and safety profile than Efavirenz in 1st-line therapy and LopinavirRitonavir in 2nd-line therapy DTG has a high genetic barrier to resistance and resistance in ART-naïve individuals treated with combination ART has so far been rare However when used as monotherapy or in people with pre-existing InSTI resistance DTG is associated with a higher risk of virologic failure and resistance
In this study the investigators aim to -
1 Identify novel mutations or novel combinations of DTG Drug Resistance Mutations DRMs
2 Identify risk factors for virologic failure development of InSTI DRMs and InSTI drug resistance
3 Check the correlations between novel resistance genotypes and phenotypic DTG resistance across HIV-1 subtypes
Adults 18 years and adolescents 10-17 years with virologic failure viral load 1000 copiesmL on any DTG-based anti-retroviral treatment 1st-line 2nd-line and 3rd-line at 20-30 clinical sites within six regions of the IeDEA cohort will be recruited into the study There is only one study visit per participant and the study is observational and embedded in routine care with no additional interventions After obtaining informed consent a blood specimen will be taken from the study participants Whole genome sequencing will be performed using the Illumina MiSeq platform to identify the Drug Resistance Mutations In addition new DRMs and mutation pathways will be explored by viral genome-wide association study and conjunctive Bayesian network approaches
In this study the investigators aim to -
1 Identify novel mutations or novel combinations of DTG Drug Resistance Mutations DRMs
2 Identify risk factors for virologic failure development of InSTI DRMs and InSTI drug resistance
3 Check the correlations between novel resistance genotypes and phenotypic DTG resistance across HIV-1 subtypes
Adults 18 years and adolescents 10-17 years with virologic failure viral load 1000 copiesmL on any DTG-based anti-retroviral treatment 1st-line 2nd-line and 3rd-line at 20-30 clinical sites within six regions of the IeDEA cohort will be recruited into the study There is only one study visit per participant and the study is observational and embedded in routine care with no additional interventions After obtaining informed consent a blood specimen will be taken from the study participants Whole genome sequencing will be performed using the Illumina MiSeq platform to identify the Drug Resistance Mutations In addition new DRMs and mutation pathways will be explored by viral genome-wide association study and conjunctive Bayesian network approaches
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None