Severely Immunocompromised HIV Patients
Conditions
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.
Interventions
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-based regimens: patients will receive an EFV-based regimen (EFV 600 mg QD + TDGF 300 mg QD + 3TC 300 mg QD)
Sponsors
Fundação Bahiana de Infectologia
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Early Mortality | 6 months | Proportion of deaths in each group |
Secondary
| Measure | Time frame |
|---|---|
| Viral Load | 24 months |
| CD4 Count | 24 months |
Countries
Brazil
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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)
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) | 92 |
| Dolutegravir Intervention: Patients will receive ART regimen based on investigational drug Dolutegravir 50 mg QD + TDF 300 mg QD+ 3TC 150 mg BID
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) | 92 |
| Total | 184 |
Baseline characteristics
| Characteristic | Efavirenz | Dolutegravir | Total |
|---|---|---|---|
| Age, Continuous | 37.3 years STANDARD_DEVIATION 8.9 | 39.3 years STANDARD_DEVIATION 11.5 | 38.3 years STANDARD_DEVIATION 10.3 |
| CD4 (cell/mm3) | 23 cells/mm3 STANDARD_DEVIATION 14 | 23 cells/mm3 STANDARD_DEVIATION 14 | 23 cells/mm3 STANDARD_DEVIATION 14 |
| Race/Ethnicity, Customized Asian | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Black | 15 Participants | 5 Participants | 20 Participants |
| Race/Ethnicity, Customized More than one race | 28 Participants | 28 Participants | 56 Participants |
| Race/Ethnicity, Customized Not reported | 28 Participants | 48 Participants | 76 Participants |
| Race/Ethnicity, Customized White | 20 Participants | 21 Participants | 41 Participants |
| Region of Enrollment Brazil | 92 Participants | 92 Participants | 184 Participants |
| Sex: Female, Male Female | 33 Participants | 63 Participants | 96 Participants |
| Sex: Female, Male Male | 59 Participants | 29 Participants | 88 Participants |
| Viral load (copies/mL | 5.6 log 10 copies/ml | 5.5 log 10 copies/ml | 5.5 log 10 copies/ml |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 9 / 92 | 13 / 92 |
| other Total, other adverse events | 0 / 92 | 11 / 92 |
| serious Total, serious adverse events | 9 / 92 | 13 / 92 |
Outcome results
Primary
Early Mortality
Proportion of deaths in each group
Time frame: 6 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Dolutegravir | Early Mortality | 9 Participants |
| Efavirenz | Early Mortality | 13 Participants |
Secondary
CD4 Count
Time frame: 24 months
Secondary
Viral Load
Time frame: 24 months