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

Study Overview
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Brief Summary
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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.

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

Conditions
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Severely Immunocompromised HIV Patients

Intervention / Treatment
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* Drug: Dolutegravir 50 mg
* Drug: Efavirenz-based regimens


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dolutegravir<br>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<br>* 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)<br>* Other names: Tivicay;|
| Active Comparator: Efavirenz<br>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<br>* Efavirenz-based regimens: patients will receive an EFV-based regimen (EFV 600 mg QD + TDGF 300 mg QD + 3TC 300 mg QD)<br>* Other names: Efavirenz;|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Viral Load |  | 24 months | 
| CD4 Count |  | 24 months |