HivDTG-ResistNCT06285110
HIV-1 Subtype-specific Drug Resistance in Patients Failing Dolutegravir (DTG) Based Regimen
An observational study of Hiv, run by University of Bern at 22 sites in 16 countries.
Trial 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 copies/mL of blood. Read more about this study
- Who is it for?
- Ages 10 years and older
- Conditions the study is for
- Hiv
- How many people
- 1,103 participants
- Where
- 22 sitesin 16 countries
- Study dates
- 13 Jun 2022to 31 Aug 2025
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 10 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: Patients routinely treated at the local HIV care clinics.
Who may be able to join
- Adults aged 18 years or older and adolescents (10-17 years)
- On any DTG-based ART regimen
- Who develop virologic failure (VF) defined as a VL >1000 copies/mL (single or confirmed measurement),
- and have signed the informed consent.
Who cannot join
- No Informed Consent
Trial locations and contacts
22 sites in 16 countries.
22 sites in 16 countries
Côte d’Ivoire2 sites
ACONDA Centre de Prise en Charge et de Formation (CePReF)
Abidjan
Centre médical de suivi des donneurs de sang, CNTS
Abidjan
Republic of the Congo2 sites
Centre de Traitement Ambulatoire
Brazzaville
Centre de Traitement Ambulatoire
Pointe-Noire
Thailand2 sites
HIV-NAT/Thai Red Cross AIDS Research Center (TRCARC)
Bangkok
Ramathibodi Hospital, Mahidol University
Bangkok
Uganda2 sites
Masaka Regional Referral Hospital / AHF Uganda Cares
Masaka
Mbarara University of Science and Technology / Mbarara ISS Clinic (MUST)
Mbarara
Brazil1 site
Instituto Nacional de Infectiologia Evandro Chagas - Fiocruz
Rio de Janeiro
Burkina Faso1 site
Hopital de Jour du Centre Hospitalier Universitaire (CHU Souro Sanou)
Bobo-Dioulasso
Cambodia1 site
National Centre for HIV/AIDS, Dermatology and STDs (NCHADS)
Phnom Penh
Mexico1 site
Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán
Mexico City
Rwanda1 site
Research for Development, Einstein-Rwanda Research and Capacity Building Program
Kigali
About this study
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)
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 copies/mL 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).
Read the 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 Lopinavir/Ritonavir 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 -
- Identify novel mutations or novel combinations of DTG Drug Resistance Mutations (DRMs).
- Identify risk factors for virologic failure, development of InSTI DRMs and InSTI drug resistance.
- 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 copies/mL) 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.
- Conditions
- Hiv
- Keywords
- HIV, Dolutegravir drug resistance mutations, Virologic failure, DTG based regimen
- Medical subject headings
- Acquired Immunodeficiency Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| People living with HIV | People living with HIV and on a Dolutegravir-based ART regimen, and experiencing treatment failure. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Type of Integrase Drug Resistance Mutations (INSTI DRMs) at the time of failing a DTG-based regimen.
The investigators define INSTI DRMs as all mutations associated with INSTIs by the Stanford HIVdb algorithm (https://hivdb.stanford.edu/). The identified mutations will be classified into major, accessory and other mutation types. New mutations will also be assessed. Analyses will be cross-sectional and differences between groups (for example, HIV-1 subtypes) tested using Pearson's chi-squared tests.
Measured: 4 years
Prevalence of Integrase Drug Resistance Mutations (INSTI DRMs) at the time of failing a DTG-based regimen.
Prevalence of the identified mutations will be expressed as the proportion of the study population showing INSTI DRMs compared to the total number of study participants experiencing treatment failure (Viral load > 1000 copies/mL and successfully sequenced). Analyses will be cross-sectional and differences between groups (for example, HIV-1 subtypes) tested using Pearson's chi-squared tests.
Measured: 4 years
Time to virologic failure
The Investigators define virologic failure as two consecutive viral load measurements of >1000 copies/mL of blood. The time to virologic failure will be analysed using survival models, stratified by country to account for heterogeneity, including all individuals who started Antiretroviral Therapy (ART) on a dolutegravir-based regimen or switched to such a regimen.
Measured: 4 years
Number of INSTI DRMs per patient
The Investigators define INSTI DRMs as all mutations associated with INSTIs by the Stanford HIVdb algorithm, including major and accessory mutations (HIV Drug Resistance Database (https://hivdb.stanford.edu/)). All individuals who developed virologic failure on any dolutegravir-based regimen will be analysed using a negative binomial generalised linear model for the number of major/accessory INSTI DRMs per patient.
Measured: 4 years
DTG drug resistance
The Investigators will use the Stanford HIV Database and the Stanford HIVdb algorithm (HIV Drug Resistance Database (https://hivdb.stanford.edu/)) to categorise drug resistance levels as susceptible (score below 10), potential low (10-14), low (15-29), intermediate (30-59), or high (≥60). An ordinal logistic regression model will be used to analyse the drug resistance levels.
Measured: 4 years
Phenotypic resistance levels of novel DRMs
Selected samples will undergo phenotypic testing to identify any correlations between the observed DRMs on HIV phenotype, which is quantified as the fold change of IC50 to DTG, i.e. the concentration at which viral replication is reduced by 50%.
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Feb 2024
- Study start13 Jun 2022
- Primary completion31 Aug 2025
- Study completion31 Aug 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for HivStudies of the same condition, open and under way.
- More trials run by University of BernThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 1,103 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Bern
- Sponsor type
- University, hospital or other
- Collaborators
- University of Zurich, ETH Zurich, University of KwaZulu, University of Bristol
- Responsible party
- Sponsor
- Investigators
- Matthias Egger, Prof. Dr., Study director, Institute of Social and Preventive Medicine (ISPM), University of Bern, SwitzerlandRichard Lessells, Dr., Principal investigator, KwaZulu-Natal Research Innovation & Sequencing Platform, University of KwaZulu-Natal, South AfricaRoger Kouyos, Prof. Dr., Principal investigator, Department of Infectious Diseases and Hospital Epidemiology, University of Zürich, SwitzerlandJonathan Sterne, Prof. Dr., Principal investigator, University of BristolNiko Beerenwinkel, Prof. Dr., Principal investigator, ETH Zurich (Switzerland)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06285110
- Sponsor's protocol ID
- DTG Resist
- Acronym
- DTG-Resist
- Status last verified
- Nov 2025
- First submitted
- 8 May 2023
- Last updated
- 25 Nov 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: The Investigators are open to share any type of study data upon reasonable request, pending approval by local sites.
Publications
Egger M, Sauermann M, Loosli T, Hossmann S, Riedo S, Beerenwinkel N, Jaquet A, Minga A, Ross J, Giandhari J, Kouyos RD, Lessells R. HIV-1 subtype-specific drug resistance on dolutegravir-based antiretroviral therapy: protocol for a multicentre study (DTG RESIST). BMJ Open. 2024 Aug 21;14(8):e085819. doi: 10.1136/bmjopen-2024-085819.
PubMed 39174068Egger M, Sauermann M, Loosli T, Hossmann S, Riedo S, Beerenwinkel N, Jaquet A, Minga A, Ross JL, Giandhari J, Kouyos R, Lessells R. HIV-1 subtype-specific drug resistance on dolutegravir-based antiretroviral therapy: protocol for a multicentre longitudinal study (DTG RESIST). medRxiv [Preprint]. 2024 May 24:2024.05.23.24307850. doi: 10.1101/2024.05.23.24307850.
PubMed 38952780
Study at a glance
From the registry record, last updated by the sponsor on 25 Nov 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT06285110
- Acronym / sponsor ID
- DTG-Resist / DTG Resist
- Conditions
- Hiv
- Keywords
- HIV, Dolutegravir drug resistance mutations, Virologic failure, DTG based regimen
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 1,103 participants (actual)
- Lead sponsor
- University of BernUniversity, hospital or other
- Collaborators
- University of Zurich, ETH Zurich, University of KwaZulu, University of Bristol
- Study start
- 13 Jun 2022 (actual)
- Primary completion
- 31 Aug 2025 (actual)
- Study completion
- 31 Aug 2025 (actual)
- First posted
- 29 Feb 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 copies/mL 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).
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 Lopinavir/Ritonavir 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 -
- Identify novel mutations or novel combinations of DTG Drug Resistance Mutations (DRMs).
- Identify risk factors for virologic failure, development of InSTI DRMs and InSTI drug resistance.
- 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 copies/mL) 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 design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| People living with HIV | – | –People living with HIV and on a Dolutegravir-based ART regimen, and experiencing treatment failure. |
Who may qualify
- Ages
- 10 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Patients routinely treated at the local HIV care clinics.
Key inclusion criteria (4 listed)
- Adults aged 18 years or older and adolescents (10-17 years)
- On any DTG-based ART regimen
- Who develop virologic failure (VF) defined as a VL >1000 copies/mL (single or confirmed measurement),
- and have signed the informed consent.
Key exclusion criteria (1 listed)
- No Informed Consent
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Type of Integrase Drug Resistance Mutations (INSTI DRMs) at the time of failing a DTG-based regimen.
Time frame: 4 years
The investigators define INSTI DRMs as all mutations associated with INSTIs by the Stanford HIVdb algorithm (https://hivdb.stanford.edu/). The identified mutations will be classified into major, accessory and other mutation types. New mutations will also be assessed. Analyses will be cross-sectional and differences between groups (for example, HIV-1 subtypes) tested using Pearson's chi-squared tests.
Prevalence of Integrase Drug Resistance Mutations (INSTI DRMs) at the time of failing a DTG-based regimen.
Time frame: 4 years
Prevalence of the identified mutations will be expressed as the proportion of the study population showing INSTI DRMs compared to the total number of study participants experiencing treatment failure (Viral load > 1000 copies/mL and successfully sequenced). Analyses will be cross-sectional and differences between groups (for example, HIV-1 subtypes) tested using Pearson's chi-squared tests.
Time to virologic failure
Time frame: 4 years
The Investigators define virologic failure as two consecutive viral load measurements of >1000 copies/mL of blood. The time to virologic failure will be analysed using survival models, stratified by country to account for heterogeneity, including all individuals who started Antiretroviral Therapy (ART) on a dolutegravir-based regimen or switched to such a regimen.
Number of INSTI DRMs per patient
Time frame: 4 years
The Investigators define INSTI DRMs as all mutations associated with INSTIs by the Stanford HIVdb algorithm, including major and accessory mutations (HIV Drug Resistance Database (https://hivdb.stanford.edu/)). All individuals who developed virologic failure on any dolutegravir-based regimen will be analysed using a negative binomial generalised linear model for the number of major/accessory INSTI DRMs per patient.
DTG drug resistance
Time frame: 4 years
The Investigators will use the Stanford HIV Database and the Stanford HIVdb algorithm (HIV Drug Resistance Database (https://hivdb.stanford.edu/)) to categorise drug resistance levels as susceptible (score below 10), potential low (10-14), low (15-29), intermediate (30-59), or high (≥60). An ordinal logistic regression model will be used to analyse the drug resistance levels.
Phenotypic resistance levels of novel DRMs
Time frame: 1 year
Selected samples will undergo phenotypic testing to identify any correlations between the observed DRMs on HIV phenotype, which is quantified as the fold change of IC50 to DTG, i.e. the concentration at which viral replication is reduced by 50%.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Nov 2025.
- Derived from this study: PubMed 39174068Egger M, Sauermann M, Loosli T, Hossmann S, Riedo S, Beerenwinkel N, Jaquet A, Minga A, Ross J, Giandhari J, Kouyos RD, Lessells R. HIV-1 subtype-specific drug resistance on dolutegravir-based antiretroviral therapy: protocol for a multicentre study (DTG RESIST). BMJ Open. 2024 Aug 21;14(8):e085819. doi: 10.1136/bmjopen-2024-085819.
- Derived from this study: PubMed 38952780Egger M, Sauermann M, Loosli T, Hossmann S, Riedo S, Beerenwinkel N, Jaquet A, Minga A, Ross JL, Giandhari J, Kouyos R, Lessells R. HIV-1 subtype-specific drug resistance on dolutegravir-based antiretroviral therapy: protocol for a multicentre longitudinal study (DTG RESIST). medRxiv [Preprint]. 2024 May 24:2024.05.23.24307850. doi: 10.1101/2024.05.23.24307850.
- Individual participant dataSharing planned: Yes. The Investigators are open to share any type of study data upon reasonable request, pending approval by local sites.
Related trials for Hiv
Not yet recruiting
HealthMpowerment Korea: Pilot Testing the Cultural Adaptation of a Digital HIV Intervention for Men Who Have Sex With Men in South Korea
HIV Infections, HIV Prevention and Care
Not yet recruiting
Prescribe to Prevent HIV: A Hybrid Trial Helping Addiction Clinics Prevent HIV & Infections Through Safer Drug Use Support
People Who Use Opioids/People With Opioid Use Disorder (OUD)
Recruiting
Evaluating the Impact of Using the B-OK Bottles for HIV and ART Literacy in South Africa
HIV, HIV Treatment
Recruiting
Trial Phase: Syndemic Adapted Medly Uganda
Mental Health
RecruitingObservational study
Olfactory Function and Model-Based Behavior in People Living With HIV and SUD
HIV, Substance Use Disorder
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Matthias Egger, Prof. Dr. study director
Institute of Social and Preventive Medicine (ISPM), University of Bern, Switzerland
Richard Lessells, Dr. principal investigator
KwaZulu-Natal Research Innovation & Sequencing Platform, University of KwaZulu-Natal, South Africa
Roger Kouyos, Prof. Dr. principal investigator
Department of Infectious Diseases and Hospital Epidemiology, University of Zürich, Switzerland
22 sites in 16 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Hiv, run by University of Bern at 22 sites in 16 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 Nov 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 22 sites in Cameroon, Côte d’Ivoire, Malawi, Republic of the Congo, Thailand and 11 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Type of Integrase Drug Resistance Mutations (INSTI DRMs) at the time of failing a DTG-based regimen. (time frame: 4 years). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06285110, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Nov 2025.