Impact of a Dolutegravir-based Regimen on Early Mortality of AIDS Patients (IDEA)

Impact of a Dolutegravir-based Regimen on Early Mortality of Severely Immunocompromised AIDS Patients

The current available antiretroviral (ARV) agents make possible a successful treatment of virtually all HIV-infected patients, but some problems related to early mortality are still of concern, mainly in resources-limited settings. There are several published reports showing that such patients are at a significantly higher risk of death during the first months of treatment, in comparison with the observed outcomes in developed countries. One of the consistently detected risks for early mortality across these reports is the baseline low CD4 count, although it does not seem to be the only reason for such outcome. In Brazil and other developing countries, there is still a large proportion of AIDS patients who are diagnosed with AIDS, or only seek health care for HIV infection late in the course of disease. Dolutegravir (DTG), the first HIV-1 integrase inhibitor, is a potent and safe ARV drug. The available evidence suggest it promotes a faster decline in HIV-1 plasma viremia, and a higher increase in CD4 cells count, in comparison with those in Efavirenz (EFV) arm. The investigators propose to compare the impact of DTG versus EFV in the early mortality rates for severely ill (CD4+ cells count <50 cells/mm3) patients starting ARV therapy.

Study Overview

• Status: Completed
• Conditions: Severely Immunocompromised HIV Patients
• Intervention / Treatment: Drug: Dolutegravir 50 mg; Drug: Efavirenz-based regimens

• Study Type: Interventional
• Enrollment (Actual): 186
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Brazil
  • Bahia
    • Salvador, Bahia, Brazil, 40010-160
      • Fundação Bahiana de Infectologia/SEI
  • RJ
    • Rio de Janeiro, RJ, Brazil
      • Universidade Federal do Rio de Janeiro
  • RS
    • Porto Alegre, RS, Brazil
      • Hospital de Clinicas de Porto Alegre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients with confirmed HIV-1 infection (positive Western blot or plasma HIV-1 RNA >1,000 copies/ml)
• No previous use of any ARV drug (drug-naïve patients)
• Presence of clinical symptoms according to Rio de Janeiro / Caracas´ AIDS definition (Asthenia, Cachexia/Wasting, Cough, Dermatitis, persistent, Diarrhea, Fever, Lymphadenopathy, Candidiasis, oral, or hairy leukoplasia, Central nervous system dysfunction, Herpes zoster in individual younger than 60 years of age)), and/or any active AIDS-defining condition
• Baseline CD4+ cells count equal or lower than 50 cells/mm3
• Age equal or higher than 18 years
• HIV-1 plasma viral load ≥ 1,000 copies of HIV-1 RNA/ml

Exclusion Criteria:

• Undetectable plasma viral load at screening
• CD4 cells count>50 cells/mm3
• Asymptomatic individuals

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dolutegravir; Intervention: Patients will receive ART regimen based on investigational drug Dolutegravir 50 mg QD + TDF 300 mg QD+ 3TC 150 mg BID	Drug: Dolutegravir 50 mg; Use of Dolutegravir -based regimens: patients will receive a Dolutegravir -based ART regimen (RAL 400 mg BID + TDF 300 mg QD + 3TC 150 mg BID); Other Names: Tivicay
Active Comparator: Efavirenz; Intervention: Patients who received ART regimen based efavirenz (EFV 600 mg QD +TDF 300 mg QD+ 3TC 300 mg QD) for one year, befor the use of DTG as SOC for first-line therapy (historic controls)	Drug: Efavirenz-based regimens; Efavirenz-based regimens: patients will receive an EFV-based regimen (EFV 600 mg QD + TDGF 300 mg QD + 3TC 300 mg QD); Other Names: Efavirenz

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Early Mortality	Proportion of deaths in each group	6 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Viral Load	24 months
CD4 Count	24 months

Collaborators and Investigators

• Sponsor: Fundação Bahiana de Infectologia

Study record dates

Study Major Dates

• Study Start (Actual): December 15, 2017
• Primary Completion (Actual): July 31, 2021
• Study Completion (Actual): September 30, 2021

Study Registration Dates

• First Submitted: April 18, 2013
• First Submitted That Met QC Criteria: April 22, 2013
• First Posted (Estimated): April 23, 2013

Study Record Updates

• Last Update Posted (Estimated): December 14, 2023
• Last Update Submitted That Met QC Criteria: March 10, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP3A Inducers; HIV Integrase Inhibitors; Integrase Inhibitors; Cytochrome P-450 CYP2B6 Inducers; Cytochrome P-450 CYP2C9 Inhibitors; Cytochrome P-450 CYP2C19 Inhibitors; Efavirenz; Dolutegravir
• Other Study ID Numbers: SevereHIV

Drug and device information, study documents

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