Immediate ART in Subjects With Opportunistic Diseases

Study Overview
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Brief Summary
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The aim of this study is to compare the clinical response and mortality rate by an opportunistic disease in HIV-infected individuals who start immediate versus conventional antiretroviral therapy. Immediate ART (iART) is defined as starting antiretroviral therapy in the first 48 hours after the hospitalization. Conventional ART (cART) is defined as starting antiretroviral therapy once the opportunistic infection is under control at the discretion of infectious disease specialist.

Detailed Description
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Sample size was calculated using formula, of difference in proportions formula using a beta of 0.1, alpha of 0.05 and an expected difference in mortality of 20%, The sample size is 225 subjects in each group. Informed consent will be obtained. Patients will be allocated to each group (iART or cART) after randomization stratified by the CD4+ T cell count (less or more than 50 cells/mm3). Plasma viral load and CD4+ T cell count will be measured at study entry and at weeks 2, 4, 12, 24 and 48 after ART initiation. Clinical outcomes will be: mortality at 4, 12, 24, and 48 weeks, length of hospitalization (measured in days), clinical and microbiological cure of the opportunistic disease, incidence and severity of immune reconstitution of inflammatory syndrome (IRIS), and adverse drug reactions and interactions. Once 50% of the sample size has completed 30 days of follow-up, a preliminary analysis will be conducted to assess safety and efficacy of iART; if differences in the mortality are observed, the study will be terminated.

Official Title
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Impact of the Timing of Antiretroviral Therapy Initiation (Immediate Versus Early) on the Mortality Rate of HIV/AIDS Patients Hospitalized With an Opportunistic Disease

Conditions
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HIV/AIDS, ANTIRETROVIRAL TREATMENT

Intervention / Treatment
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* Other: iART
* Other: cART


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Over 18 years old Time from admission to study entry: less than 48 hours Confirmed HIV diagnosis or high probability of HIV infection based on a positive HIV rapid test Having an opportunistic disease Subjects must be naïve to ART or have failed their first or second ART regimen or must have abandoned ART for more than 3 months Exclusion Criteria: Meningitis due to Cryptococcus spp. or for M. tuberculosis Pregnancy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 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
Interventional Model Description: Stratified randomization will be generated by an electronic system, in blocks of 6 and 8, and a 1:1 ratio, according to the CD4+ T cell count. Group A: Immediate treatment (iART). Start ART within 48 hours of admission and hospitalization; Group B: Conventional treatment (cART). Start the ART once the opportunistic infection is under control at the discretion of infectious disease specialist.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group A Immediate treatment (iART)<br>Other: time to start the ART within 48 hours of admission to hospitalization | Other: iART<br>* After group assignment, ART will be started within the first 48 hours after admission to the hospital. ART regimen will be decided according to each subject´s the clinical characteristics<br>|
| Active Comparator: Group B Conventional treatment (cART)<br>Other: time to start the ART, after the opportunistic disease has been controlled, at the discretion of infectious disease specialist. | Other: cART<br>* After group assignment, ART is started at the discretion of the attending physician. ART regimen will be decided according to each subject´s the clinical characteristics<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mortality | Compare mortality rates betweeno two groups according to the timing of ART initiation: immediate antiretroviral therapy (iART) versus conventional antiretroviral therapy (cART) | 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assess survival rates | Compare the survival rate of HIV-infected patients on immediate antiretroviral therapy (iART) versus conventional antiretroviral therapy (cART) | 90 days since starting antiretroviral therapy (ART) | 
| Assess survival rates | Compare the survival rate of HIV-infected patients on immediate antiretroviral therapy (iART) versus conventional antiretroviral therapy (cART) | 180 days since starting antiretroviral therapy (ART) | 
| Assess survival rates | Compare the survival rate of HIV-infected patients on immediate antiretroviral therapy (iART) versus conventional antiretroviral therapy (cART) | 360 days since starting antiretroviral therapy (ART) | 
| Length of stay | Compare length of hospitalization between both groups | 1 year | 
| Asses survival rates by the CD4 count | Compare the survival rate of HIV-infected patients on immediate antiretroviral therapy (iART) versus conventional antiretroviral therapy (cART) stratified by CD4+ T cell count at study entry | 90 days | 
| Asses survival rates by the CD4 count | Compare the survival rate of HIV-infected patients on immediate antiretroviral therapy (iART) versus conventional antiretroviral therapy (cART) stratified by CD4+ T cell count at study entry | 180 days | 
| Asses survival rates by the CD4 count | Compare the survival rate of HIV-infected patients on immediate antiretroviral therapy (iART) versus conventional antiretroviral therapy (cART) stratified by CD4+ T cell count at study entry | 360 days | 
| Viral load | Measure the baseline plasma viral load and evaluate its dynamics after ART initiation in both groups | 90 days | 
| Viral load | Measure the baseline plasma viral load and evaluate its dynamics after ART initiation in both groups | 180 days | 
| Viral load | Measure the baseline plasma viral load and evaluate its dynamics after ART initiation in both groups | 360 days | 
| CD4 T cell counts | Measure CD4+ T cell counts, and evaluate its dynamics after ART initiation in both groups | 90 days | 
| CD4 T cell counts | Measure CD4+ T cell counts, and evaluate its dynamics after ART initiation in both groups | 180 days | 
| CD4 T cell counts | Measure CD4+ T cell counts, and evaluate its dynamics after ART initiation in both groups | 360 days | 
| IRIS | Determine the incidence and severity of IRIS. Severity will be classified as mild or life threatening | 48 weeks | 
| Adverse reactions | Describe ART-related adverse events, and drug interactions | 48 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV/AIDS, ART