NCT04326504

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.

Trial Health

57
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
5,000

participants targeted

Target at P75+ for all trials

Timeline
Completed

Started Feb 2021

Longer than P75 for all trials

Geographic Reach
1 country

3 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

March 26, 2020

Completed
4 days until next milestone

First Posted

Study publicly available on registry

March 30, 2020

Completed
10 months until next milestone

Study Start

First participant enrolled

February 1, 2021

Completed
3.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 31, 2024

Completed
2 months until next milestone

Study Completion

Last participant's last visit for all outcomes

February 28, 2025

Completed
Last Updated

February 26, 2024

Status Verified

February 1, 2024

Enrollment Period

3.9 years

First QC Date

March 26, 2020

Last Update Submit

February 22, 2024

Conditions

HIV InfectionsClinical OutcomesAdverse Drug EventEffect of Drugs

Outcome Measures

Primary Outcomes (2)

  • frequency of therapy discontinuation due to any event for patients starting ART

    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)

    36 months

  • therapy discontinuation due to any event for ART-eprerienced patients starting DTG-based regimens

    therapy discontinuation due to any event for ART-experienced patients

    36 months

Secondary Outcomes (4)

  • Exploratory outcomes

    36 months

  • Changes in quality of life for patients switching to DTG-based regimens

    6 and 12 months

  • HIV drug resistance

    36 months

  • Markers of CVD risk

    36 months

Study Arms (4)

Patients starting DTG-based regimens

ART-naïve patients, starting cART regimens based on DTG

Other: No intervention

Switch cohort

Patients on stable ART regimens switching to DTG (any reason)

Other: No intervention

Therapy failure

ART-experienced patients switching to DTG-containing regimens due to virological failure

Other: No intervention

Non-DTG group

Patients who started a non-DTG containing regimen

Other: No intervention

Interventions

No interventionOTHER

This will be an observational study, no intervention will be performed

Non-DTG groupPatients starting DTG-based regimensSwitch cohortTherapy failure

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)
Sampling MethodProbability Sample
Study Population

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).

You may qualify if:

  • 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.

You may not qualify if:

  • Any previous use of ART (drug-naïve group only).
  • Current imprisonment, or compulsory detention (involuntary incarceration). For treatment of a psychiatric or physical illness.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (3)

Fundação Bahiana de Infectologia/SEI

Salvador, Estado de Bahia, 40010-160, Brazil

RECRUITING

Fundação Bahiana de Infectologia

Salvador, Estado de Bahia, 40110160, Brazil

RECRUITING

Centro de Referência e Treinamento

São Paulo, São Paulo, 04121-000, Brazil

RECRUITING

Related Publications (11)

  • Dutertre M, Cuzin L, Demonchy E, Pugliese P, Joly V, Valantin MA, Cotte L, Huleux T, Delobel P, Martin-Blondel G; Dat'AIDS Study Group. Initiation of Antiretroviral Therapy Containing Integrase Inhibitors Increases the Risk of IRIS Requiring Hospitalization. J Acquir Immune Defic Syndr. 2017 Sep 1;76(1):e23-e26. doi: 10.1097/QAI.0000000000001397. No abstract available.

    PMID: 28418992RESULT

  • de Boer MG, van den Berk GE, van Holten N, Oryszcyn JE, Dorama W, Moha DA, Brinkman K. Intolerance of dolutegravir-containing combination antiretroviral therapy regimens in real-life clinical practice. AIDS. 2016 Nov 28;30(18):2831-2834. doi: 10.1097/QAD.0000000000001279.

    PMID: 27824625RESULT

  • Ciccullo A, Baldin G, Cossu MV, Passerini M, Borghetti A, Capetti A, Di Giambenedetto S. Dolutegravir Plus Lamivudine as First-Line Regimen in a Multicenter Cohort of HIV-1-Infected Patients: Preliminary Data from Clinical Practice. AIDS Res Hum Retroviruses. 2020 Jan;36(1):4-5. doi: 10.1089/AID.2019.0147. Epub 2019 Sep 30. No abstract available.

    PMID: 31476877RESULT

  • Elzi L, Erb S, Furrer H, Cavassini M, Calmy A, Vernazza P, Gunthard H, Bernasconi E, Battegay M; Swiss HIV Cohort Study Group. Adverse events of raltegravir and dolutegravir. AIDS. 2017 Aug 24;31(13):1853-1858. doi: 10.1097/QAD.0000000000001590.

    PMID: 28692533RESULT

  • Hoffmann C, Welz T, Sabranski M, Kolb M, Wolf E, Stellbrink HJ, Wyen C. Higher rates of neuropsychiatric adverse events leading to dolutegravir discontinuation in women and older patients. HIV Med. 2017 Jan;18(1):56-63. doi: 10.1111/hiv.12468. Epub 2016 Nov 10.

    PMID: 27860104RESULT

  • Norwood J, Turner M, Bofill C, Rebeiro P, Shepherd B, Bebawy S, Hulgan T, Raffanti S, Haas DW, Sterling TR, Koethe JR. Brief Report: Weight Gain in Persons With HIV Switched From Efavirenz-Based to Integrase Strand Transfer Inhibitor-Based Regimens. J Acquir Immune Defic Syndr. 2017 Dec 15;76(5):527-531. doi: 10.1097/QAI.0000000000001525.

    PMID: 28825943RESULT

  • Taramasso L, Ricci E, Menzaghi B, Orofino G, Passerini S, Madeddu G, Martinelli CV, De Socio GV, Squillace N, Rusconi S, Bonfanti P, Di Biagio A; CISAI Study Group. Weight Gain: A Possible Side Effect of All Antiretrovirals. Open Forum Infect Dis. 2017 Nov 3;4(4):ofx239. doi: 10.1093/ofid/ofx239. eCollection 2017 Fall.

    PMID: 29255735RESULT

  • Zash R, Makhema J, Shapiro RL. Neural-Tube Defects with Dolutegravir Treatment from the Time of Conception. N Engl J Med. 2018 Sep 6;379(10):979-981. doi: 10.1056/NEJMc1807653. Epub 2018 Jul 24. No abstract available.

    PMID: 30037297RESULT

  • American Diabetes Association. 2. Classification and Diagnosis of Diabetes: Standards of Medical Care in Diabetes-2019. Diabetes Care. 2019 Jan;42(Suppl 1):S13-S28. doi: 10.2337/dc19-S002.

    PMID: 30559228RESULT

  • Cruz LN, Fleck MP, Oliveira MR, Camey SA, Hoffmann JF, Bagattini AM, Polanczyk CA. Health-related quality of life in Brazil: normative data for the SF-36 in a general population sample in the south of the country. Cien Saude Colet. 2013 Jul;18(7):1911-21. doi: 10.1590/s1413-81232013000700006.

    PMID: 23827895RESULT

  • Laguardia J, Campos MR, Travassos C, Najar AL, Anjos LA, Vasconcellos MM. Brazilian normative data for the Short Form 36 questionnaire, version 2. Rev Bras Epidemiol. 2013 Dec;16(4):889-97. doi: 10.1590/s1415-790x2013000400009. English, Portuguese.

    PMID: 24896594RESULT

MeSH Terms

Conditions

HIV InfectionsDrug-Related Side Effects and Adverse Reactions

Condition Hierarchy (Ancestors)

Blood-Borne InfectionsCommunicable DiseasesInfectionsSexually Transmitted Diseases, ViralSexually Transmitted DiseasesLentivirus InfectionsRetroviridae InfectionsRNA Virus InfectionsVirus DiseasesGenital DiseasesUrogenital DiseasesImmunologic Deficiency SyndromesImmune System DiseasesChemically-Induced Disorders

Central Study Contacts

Carlos Brites, MD, PhD

CONTACT

557132838123crbrites@gmail.com

Estela Luz, RN, MPH

CONTACT

557132838123eluz5@yahoo.com.br

Study Design

Study Type
observational
Observational Model
COHORT
Time Perspective
PROSPECTIVE
Target Duration
36 Months
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

March 26, 2020

First Posted

March 30, 2020

Study Start

February 1, 2021

Primary Completion

December 31, 2024

Study Completion

February 28, 2025

Last Updated

February 26, 2024

Record last verified: 2024-02

Data Sharing

IPD Sharing
Will not share

Locations

BR(3)