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

Phase 2

Completed

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.

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
Dolutegravir	Dolutegravir 50 mg	Intervention: Patients will receive ART regimen based on investigational drug Dolutegravir 50 mg QD + TDF 300 mg QD+ 3TC 150 mg BID
Efavirenz	Efavirenz-based regimens	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)

Primary Outcome Measures

Name	Time	Method
Early Mortality	6 months	Proportion of deaths in each group

Secondary Outcome Measures

Name	Time	Method
Viral Load	24 months
CD4 Count	24 months

Locations (3): Fundação Bahiana de Infectologia/SEI
🇧🇷
Salvador, Bahia, Brazil
Universidade Federal do Rio de Janeiro
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Rio de Janeiro, RJ, Brazil
Hospital de Clinicas de Porto Alegre
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Porto Alegre, RS, Brazil