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

NCT01837277 | Completed Phase 2 Results

• 1 other identifier: SevereHIV
• Study Type: interventional
• Target: 186
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

Severely Immunocompromised HIV Patients

Outcome Measures

Primary Outcomes (1)

• Early Mortality

  Proportion of deaths in each group

  6 months

Secondary Outcomes (2)

• Viral Load

  24 months

• CD4 Count

  24 months

Study Arms (2)

Dolutegravir

EXPERIMENTAL

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

Efavirenz

ACTIVE COMPARATOR

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

Interventions

Dolutegravir 50 mg DRUG

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)

Also known as: Tivicay

Dolutegravir

Efavirenz-based regimens DRUG

Efavirenz-based regimens: patients will receive an EFV-based regimen (EFV 600 mg QD + TDGF 300 mg QD + 3TC 300 mg QD)

Also known as: Efavirenz

Efavirenz

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

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

Sponsors & Collaborators

• Fundação Bahiana de Infectologia: lead

Study Sites (3)

Fundação Bahiana de Infectologia/SEI

Salvador, Estado de Bahia, 40010-160, Brazil

Location

Universidade Federal do Rio de Janeiro

Rio de Janeiro, Rio de Janeiro, Brazil

Location

Hospital de Clinicas de Porto Alegre

Porto Alegre, Rio Grande do Sul, Brazil

Location

MeSH Terms

Interventions

dolutegravir; efavirenz

Results Point of Contact

• Title: Professor Carlos Brites
• Organization: Federal University of Bahia

crbrites@hotmail.com

+5555992329552

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Senior Investigator

Study Record Dates

• First Submitted: April 18, 2013
• First Posted: April 23, 2013
• Study Start: December 15, 2017
• Primary Completion: July 31, 2021
• Study Completion: September 30, 2021
• Last Updated: December 14, 2023
• Results First Posted: December 14, 2023

Record last verified: 2023-03

Locations

BR (3)