Resistance Profile to Antiretroviral Medications in Individuals Living With HIV Who Failed a First-Line Regimen With Tenofovir / Lamivudina and Dolutegravir in Brasil (ARDOL)

The goal of this study is to understand the profile of individuals who demonstrate transmitted drug resistance to Dolutegravir (DTG) among PLHIV in Brazil in terms of the subtypes of virus and other individual characteristics after 24 weeks of treatment with a regimen of DTG, Tenofovir, and Lamivudine (TL+D). The study also seeks to determine what alterations occur in the 3'-PPT region of the HIV virus in patients with failing the TL+D regimen.

The test group will be compared to a control group of individuals randomly selected whose viral control remains below detection limit (50 copies/mL) for 24 weeks after the initiation of treatment. The study uses clinics in cities in each of the five regions of Brazil: South region (Porto Alegre, Viamão), Southeast region (São Paulo, Santos, Guarujá), Northeast region (Salvador), Center West region (Brasília), and the North region (Manaus). Porto Alegre and Viamão are of interest because of the strong presence of subtype C in the South region. Salvador is a focus for subtype F of HIV. Finally, in Santos there is a strong presence of recombinant forms of subtypes F and B. These non-B subtypes are important to the study as they are typical of other medium and low income countries.

The plan for the study includes 200 cases who will receive the TL+D medication for 24 weeks (50 in each region) and 400 controls again spread among the regions on a 1 (case): 2(control ratio.

Study Overview

• Status: Completed
• Conditions: HIV; HIV -1 Infection
• Intervention / Treatment: Drug: TL+D antiretroviral

Detailed Description

In November 2018, 170,000 individuals were receiving Dolutegravir through the public health system. It is a public health priority to evaluate the risk of virological failure and the subsequent development of resistance to integrase inhibitors in our setting. It has recently been shown that, in addition to resistance mutations in the integrase region of the pol gene, mutations in the 3'-PPT region (nef gene) also emerge and contribute to decreased susceptibility to Dolutegravir. The objectives of this work are to investigate the influence of transmitted antiretroviral resistance, the profile of HIV subtypes, and immunological and virological characteristics among individuals who failed first-line treatment with Tenofovir/Lamivudine and Dolutegravir (TL+D) after 24 weeks of treatment in Brazil. We also seek to determine the genotypic resistance profile among individuals who failed the first-line TL+D regimen after 24 weeks of treatment in Brazil. To determine what alterations in the 3'-PPT are observed in viruses from patients failing TL+D and to assess if this new resistance pathway contributes to acquired resistance to the drug in clinical practice.

This is a nested case-control prospective study comparing in a 2:1 ratio the baseline HIV-1 genotypic profile of individuals with virological failure on the TL+D regimen after 24 weeks of treatment (cases) to randomly selected individuals with viral control with viral load below the detection limits of 50 copies/mL, 24 weeks after treatment initiation (controls).

HYPOTHESIS: The central hypothesis is that transmitted drug resistance (TDR) may be associated with and contribute to virological failure with dolutegravir (DTG) in clinical practice. To test this central hypothesis, we will identify DTG-containing regimens with failure in people living with HIV in Brazil, a model country for large-scale DTG implementation, where multiple HIV subtypes cocirculate.

PRIMARY RESEARCH OBJECTIVE:

1. Investigate the influence of transmitted drug resistance, the profile of HIV subtypes, and immunological and virological characteristics among individuals who failed the first-line TL+D regimen after 24 weeks of treatment in Brazil.
2. Determine the genotypic resistance profile among individuals who failed first-line TL+D after 24 weeks of treatment in Brazil.
3. Determine what alterations in the 3'-PPT are observed in viruses from patients failing TL+D and assess if this new resistance pathway contributes to acquired drug resistance in clinical practice.

RISK AND BENEFIT ASSESSMENT:

RISKS: The risks associated with this study include discomfort at the needle puncture site for blood draws or the possible appearance of a bruise. Discomfort or occasional bruising occur with the same frequency as any blood draw for exams that a patient is already accustomed to.

BENEFITS: Patients will receive no direct benefit from participation in this study. The resistance tests performed may eventually help in selecting more effective antiretroviral drugs if treatment is not fully effective in controlling the HIV in the body. There will be no financial costs or compensation for participation in this study.

• Study Type: Interventional
• Enrollment (Actual): 777
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Brazil
  • Amazonas
    • Manaus, Amazonas, Brazil, 69040-000
      • Fundação de Medicina Tropical Doutor Heitor Vieira Dourado
  • Estado de Bahia
    • Salvador, Estado de Bahia, Brazil, 40100-160
      • Centro Estadual Especializado em Diagnóstico, Assistência e Pesquisa (CEDAP)
  • Federal District
    • Brasília, Federal District, Brazil, 70351-580
      • Centro Especializado em Doenças Infecciosas (CEDIN-DF)
  • Rio Grande do Sul
    • Porto Alegre, Rio Grande do Sul, Brazil, 91350-200
      • Hospital Nossa Senhora da Conceição
    • Porto Alegre, Rio Grande do Sul, Brazil, 90040-000
      • LADI - Laboratório de Apoio Diagnóstico em Infectologia (Hospital Universitário Miguel Riet Corrêa Jr)
    • Viamão, Rio Grande do Sul, Brazil, 94480-560
      • Serviço Especializado em IST/HIV/AIDS Viamão
  • São Paulo
    • Guarujá, São Paulo, Brazil, 11471-000
      • Unidade de Infectologia William Rocha
    • São Paulo, São Paulo, Brazil, 08270-070
      • Hospital Santa Marcelina
    • São Paulo, São Paulo, Brazil, 04039-032
      • Retrovirology Laboratory - UNIFESP

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Age between 18 and 70 ART therapy naive

Exclusion Criteria:

Resistant to reverse transcriptase inhibitor drugs (NRTI)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: TL+D; TL+D regimen of antiretroviral drugs for 24 weeks	Drug: TL+D antiretroviral; Patients will receive the Tenofovir/Lamiduvine NRTI drugs along with the Dolutegravir for 24 weeks.
No Intervention: Control; Individuals chosen who have not failed an HIV drug regimen

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prevalence of TDR	Comparative analysis of transmitted drug resistance between arms of the study	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Distribution of subtypes among regions	The distribution of subtypes in the five regions of Brazil in light of existence or not of TDR	4 months
Sequence of 3'-PPT region of NEF	Comparison of the sequence of the 3'-PPT region of the NEF gene related to the existence of TDR, subtype and region	6 months
Viral Load	Descriptive analysis of viral load for cases and controls at baseline, week 12 and week 24, including comparison related to presence of TDR and subtypes	6 months
CD4+ Levels	Analysis of CD4+ levels at baseline, week 12 and week 24 in relation to presence of TDR, subtype and region	6 months

Collaborators and Investigators

• Sponsor: Federal University of São Paulo
• Collaborators: Gilead Sciences

Study record dates

Study Major Dates

• Study Start (Actual): April 13, 2022
• Primary Completion (Actual): March 8, 2024
• Study Completion (Actual): March 8, 2024

Study Registration Dates

• First Submitted: May 25, 2026
• First Submitted That Met QC Criteria: May 25, 2026
• First Posted (Actual): June 1, 2026

Study Record Updates

• Last Update Posted (Actual): June 1, 2026
• Last Update Submitted That Met QC Criteria: May 25, 2026
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Keywords: DTG; subtype; TDR; transmitted drug resistance
• Other Study ID Numbers: SPARC-10

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The sponsors plan to divulge all the anonymized data through a publicly available repository at a site to be determined.
• IPD Sharing Time Frame: The IPD will be available by June 2026 and stay publicly available for 10 years (until May 2036).
• IPD Sharing Access Criteria: Access will be publicly available and include all the data from the project. Access will be by accessing the public repository.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No