HIV-1 Subtype-specific Drug Resistance in Patients Failing Dolutegravir (DTG) Based Regimen

NCT06285110 | Completed

• 1 other identifier: DTG Resist
• Study Type: observational
• Target: 1,103
• Locations: 15 countries
• Sites: 20

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 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).

Conditions

Hiv

Keywords

HIV; Dolutegravir drug resistance mutations; Virologic failure; DTG based regimen

Outcome Measures

Primary Outcomes (6)

• 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.

  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.

  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.

  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.

  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.

  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%.

  1 year

Study Arms (1)

People living with HIV

People living with HIV and on a Dolutegravir-based ART regimen, and experiencing treatment failure.

Eligibility Criteria

• Age: 10 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Patients routinely treated at the local HIV care clinics.

You may qualify if:

• 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.

You may not qualify if:

• No Informed Consent

Sponsors & Collaborators

• University of Bern: lead
• University of Zurich: collaborator
• ETH Zurich: collaborator
• University of KwaZulu: collaborator
• University of Bristol: collaborator

Study Sites (22)

Centro Medico Huesped

Buenos Aires, Argentina

Location

Instituto Nacional de Infectiologia Evandro Chagas - Fiocruz

Rio de Janeiro, Brazil

Location

Hopital de Jour du Centre Hospitalier Universitaire (CHU Souro Sanou)

Bobo-Dioulasso, Burkina Faso

Location

National Centre for HIV/AIDS, Dermatology and STDs (NCHADS)

Phnom Penh, Cambodia

Location

Regional Hospital Limbe

Limbe, Cameroon

Location

Hospital Jamot

Yaoundé, Cameroon

Location

ACONDA Centre de Prise en Charge et de Formation (CePReF)

Abidjan, Côte d’Ivoire

Location

Centre médical de suivi des donneurs de sang, CNTS

Abidjan, Côte d’Ivoire

Location

Moi University, AMPATH

Eldoret, Kenya

Location

Lighthouse clinic

Lilongwe, Malawi

Location

Martin Preuss Centre

Lilongwe, Malawi

Location

Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán

Mexico City, Mexico

Location

Centre de Traitement Ambulatoire

Brazzaville, Republic of the Congo

Location

Centre de Traitement Ambulatoire

Pointe-Noire, Republic of the Congo

Location

Research for Development, Einstein-Rwanda Research and Capacity Building Program

Kigali, Rwanda

Location

National Institute for Medical Research (NIMR)

Kisesa, Tanzania

Location

HIV-NAT/Thai Red Cross AIDS Research Center (TRCARC)

Bangkok, Thailand

Location

Ramathibodi Hospital, Mahidol University

Bangkok, Thailand

Location

Masaka Regional Referral Hospital / AHF Uganda Cares

Masaka, Uganda

Location

Mbarara University of Science and Technology / Mbarara ISS Clinic (MUST)

Mbarara, Uganda

Location

Centre for Infectious Disease Research Zambia (CIDRZ)

Lusaka, Zambia

Location

Newlands Clinic

Harare, Zimbabwe

Location

Related Publications (2)

• 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.

  PMID: 39174068 DERIVED

• Egger 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.

  PMID: 38952780 DERIVED

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome

Condition Hierarchy (Ancestors)

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Study Officials

• Matthias Egger, Prof. Dr.

  Institute of Social and Preventive Medicine (ISPM), University of Bern, Switzerland

  STUDY DIRECTOR

• Richard Lessells, Dr.

  KwaZulu-Natal Research Innovation & Sequencing Platform, University of KwaZulu-Natal, South Africa

  PRINCIPAL INVESTIGATOR

• Roger Kouyos, Prof. Dr.

  Department of Infectious Diseases and Hospital Epidemiology, University of Zürich, Switzerland

  PRINCIPAL INVESTIGATOR

• Jonathan Sterne, Prof. Dr.

  University of Bristol

  PRINCIPAL INVESTIGATOR

• Niko Beerenwinkel, Prof. Dr.

  ETH Zurich (Switzerland)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 8, 2023
• First Posted: February 29, 2024
• Study Start: June 13, 2022
• Primary Completion: August 31, 2025
• Study Completion: August 31, 2025
• Last Updated: November 25, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ANALYTIC CODE
• Time Frame: Within 1 year of study conclusion, for about 1 year.
• Access Criteria: Upon reasonable request, pending approval by local sites.

Locations

ME (1); TH (2); RE (2); AR (1); ZI (1); CA (1); RW (1); ZA (1); BR (1); KE (1); MA (2); UG (2); TA (1); CÔ (2); BU (1)