Dolutegravir and Clinical Outcomes Among ART-recipients in Brazil

HIV Infections Clinical Trial

— CODE  

Official title:

Dolutegravir and Clinical Outcomes Among ART-recipients in Brazil: A Population-based Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04326504
• Other study ID #: FBAI
• Status: Recruiting
• Start date: February 1, 2021
• Est. completion date: February 28, 2025

Study information

• Verified date: February 2024
• Source: Fundação Bahiana de Infectologia
• Contact: Carlos Brites, MD, PhD
• Phone: 557132838123
• Email: crbrites[@]gmail.com
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 5000
• Est. completion date: February 28, 2025
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Adverse Drug Event
• Clinical Outcomes
• Drug-Related Side Effects and Adverse Reactions
• Effect of Drugs
• HIV Infections

Intervention

Other:
• No intervention
This will be an observational study, no intervention will be performed

Locations

Country	Name	City	State
Brazil	Fundação Bahiana de Infectologia	Salvador	BA
Brazil	Fundação Bahiana de Infectologia/SEI	Salvador	Bahia
Brazil	Centro de Referência e Treinamento	São Paulo	SP

Sponsors (14)

Lead Sponsor

Collaborator

Fundação Bahiana de Infectologia

Centro de Referência e Tratamento, CRT, São Paulo, SP, Faculdade de Medicina de Botucatu, Unesp, Fundação de Medicina Tropical de Manaus, Fundação Universidade de Caxias do Sul - FUCS/RS, Hospital das Clínicas da Faculdade de Medicina de Ribeirao Preto/USP, Hospital de Clinicas de Porto Alegre, Hospital Partenon, Porto Alegre, Hospital Universitário Cassiano Antônio de Moraes/HUCAM, Instituto Infectologia Evandro Chagas, Rio de Janeiro, Sociedade Campineira de Educação e Instrução - Campinas, Universidade Federal do Rio Grande do Norte, Universidade Municipal de São Caetano do Sul, University of New Mexico

Country where clinical trial is conducted

Brazil, 

References & Publications (11)

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. — View Citation

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 Retroviru — View Citation

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. — View Citation

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. — View Citation

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 Hospitalizati — View Citation

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. — View Citation

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 N — View Citation

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. — View Citation

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 Acq — View Citation

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 No — View Citation

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. — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	Exploratory outcomes	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.	36 months
Secondary	Changes in quality of life for patients switching to DTG-based regimens	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.	6 and 12 months
Secondary	HIV drug resistance	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.	36 months
Secondary	Markers of CVD risk	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.	36 months