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

NCT ID: NCT01837277

Last Updated: 2023-12-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 186 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-12-15
• Study Completion Date: 2021-09-30

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Dolutegravir

Intervention: Patients will receive ART regimen based on investigational drug Dolutegravir 50 mg QD + TDF 300 mg QD+ 3TC 150 mg BID

Group Type: EXPERIMENTAL

Dolutegravir 50 mg

Intervention Type: 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)

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)

Group Type: ACTIVE_COMPARATOR

Efavirenz-based regimens

Intervention Type: DRUG

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

Interventions

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)

Intervention Type: 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)

Intervention Type: DRUG

Other Intervention Names

Tivicay; Efavirenz

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Fundação Bahiana de Infectologia

OTHER

Sponsor Role: lead

Responsible Party

Carlos Brites

Senior Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Fundação Bahiana de Infectologia/SEI

Salvador, Estado de Bahia, Brazil

Universidade Federal do Rio de Janeiro

Rio de Janeiro, Rio de Janeiro, Brazil

Hospital de Clinicas de Porto Alegre

Porto Alegre, Rio Grande do Sul, Brazil

Countries

Brazil

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

SevereHIV

Identifier Type: -

Identifier Source: org_study_id