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Dolutegravir and Clinical Outcomes Among ART-recipients in Brazil

Recruiting
Conditions
Adverse Drug Event
Clinical Outcomes
HIV Infections
Effect of Drugs
Interventions
Other: No intervention
Registration Number
NCT04326504
Lead Sponsor
Fundação Bahiana de Infectologia
Brief Summary

Access to antiretroviral therapy (ART) in low-income and middle-income countries has been scaled-up effectively over recent years. Recently, the World Health Organization (WHO) guidelines changed to recommend the use of Dolutegravir (DTG) combined with two nucleoside reverse transcriptase inhibitors (NRTIs), tenofovir and lamivudine, for first-line ART; however, there is still a need for further data on the outcomes of DTG-based regimens for people with HIV-1.

This study aims to describe the outcomes of drug-naïve and experienced patients starting a dolutegravir (DTG)-based regimen in a large cohort of HIV - infected patients in Brazil and compare to outcomes obtained from a retrospective control group of subjects who initiated non-DTG-based ART.

Detailed Description

CODE is a multicenter prospective observational study to describe and quantify the outcomes of patients starting DTG-based regimens. The investigators will follow ART-naïve patients starting DTG-based regimens (Group 1), patients on stable ART regimens switching to DTG (any reason) (Group 2), and ART-experienced patients switching to DTG-containing regimens due to virological failure (Group 3). In addition, for comparison purposes, the investigators will collect data on patients who started a non-DTG containing regimen (Group 4) in the period for 2014-2016 and did not switch to DTG-based regimens (Figure 1). Enrolled patients will be followed for 36 months.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
5000
Inclusion Criteria
  • • Signed informed consent.

    • HIV infection documented by plasma HIV RNA viral load, a rapid HIV test or any licensed ELISA test; and confirmed by another test using a different method, including but not limited to a rapid HIV test, Western Blot, HIV culture, HIV antigen, or HIV pro-viral DNA at any time prior to study entry.
    • Age ≥ 15 years.
    • For women of child-bearing potential, willingness to use effective contraceptives.
    • Starting use of DTG-based regimen, or being initiated on a non-DTG based ART between 2014 - 2016.
Exclusion Criteria
  • • Any previous use of ART (drug-naïve group only).

    • Current imprisonment, or compulsory detention (involuntary incarceration). For treatment of a psychiatric or physical illness.

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Arm && Interventions
GroupInterventionDescription
Therapy failureNo interventionART-experienced patients switching to DTG-containing regimens due to virological failure
Non-DTG groupNo interventionPatients who started a non-DTG containing regimen
Patients starting DTG-based regimensNo interventionART-naïve patients, starting cART regimens based on DTG
Switch cohortNo interventionPatients on stable ART regimens switching to DTG (any reason)
Primary Outcome Measures
NameTimeMethod
frequency of therapy discontinuation due to any event for patients starting ART36 months

The key outcomes of interest include treatment discontinuation due to any event as well as specifically due to metabolic and psychiatric events, virologic outcomes (viral suppression at 12 months, failure to ART, and genotypic results of acquired resistance), clinical outcomes (including noted side effects, retention in care, death, weight changes, hyperglycemia, diabetes, lipid changes, AIDS-defining illnesses, and recorded psychiatric and CNS effects), and special outcomes / populations (pregnancy outcomes, IRIS events, changes in HRQoL, viral hepatitis flares, and tuberculosis outcomes)

therapy discontinuation due to any event for ART-eprerienced patients starting DTG-based regimens36 months

therapy discontinuation due to any event for ART-experienced patients

Secondary Outcome Measures
NameTimeMethod
Exploratory outcomes36 months

These clinical outcomes include: all-cause mortality; all AIDS-defining events; all types of cancer; bacterial pneumonia; pulmonary embolism; deep vein thrombosis; new-onset diabetes mellitus (as defined by the ADA criteria);10 coronary artery disease requiring drug treatment; congestive heart failure; peripheral vascular disease; fractures; and solicited adverse events.

Markers of CVD risk36 months

Assessments will be made of blood lipids, smoking, blood pressure, incidence of diabetes mellitus, use of medication to lower blood pressure and lipids, and the use of aspirin, to assist in the evaluation of cardiovascular risks and benefits of early treatment.

Changes in quality of life for patients switching to DTG-based regimens6 and 12 months

Physical and Mental Components Scores will be measured. HRQoL evaluation will be performed only for patients switching to DTG-based regimens, at the time switch occurs (baseline), and after 6 and 12 months of follow up.

HIV drug resistance36 months

This outcome will be evaluated by collecting samples of blood prior to starting DTG-based ART. These tests will not be done in real time, and results will not be given to the investigator or participant. Once virological failure is identified, the baseline sample will be used to assess transmitted drug resistance through comparison with current resistance genotypic tests. Key mutations that are associated with viral resistance will be determined using information periodically updated by the International AIDS Society.

Trial Locations

Locations (3)

Centro de Referência e Treinamento

🇧🇷

São Paulo, SP, Brazil

Fundação Bahiana de Infectologia

🇧🇷

Salvador, BA, Brazil

Fundação Bahiana de Infectologia/SEI

🇧🇷

Salvador, Bahia, Brazil

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