Simultaneous Versus Sequential Antiretroviral Therapy (ARV) Therapy and Mycobacterium Tuberculosis (MTB) Treatment

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to evaluate and compare the efficacy of immediate antiretroviral therapy versus 2 month deferred anti-Tb therapy upon the clinical course of tuberculosis and HIV infection in patients with AIDS and active tuberculosis.

Detailed Description
-----------------
AIDS and tuberculosis are two international and national priority public health problems. The best time for starting antiretroviral therapy in patients with AIDS and active tuberculosis is not clear, despite of the guidelines regarding CD4+ count. The debate surrounding this issue is mainly due to the difficulty among adherence of anti-MTb and anti-HIV treatment, the pharmacological interaction, the adverse events related to drugs and the risk of inflammatory reconstitution syndrome, especially in patients with advanced HIV infection. Moreover, there is great debate upon the lack of knowledge of the degree of immune reconstitution throughout time against Mtb induced by the anti-HIV therapy.

Official Title
-----------------
Efficacy of Simultaneous Versus Sequential Antiretroviral Therapy and Antituberculosis Treatment in Patients With AIDS and Active Tuberculosis. Open, Randomized and Controlled, Multisite Clinical Trial.

Conditions
-----------------
HIV, AIDS, Tuberculosis

Intervention / Treatment
-----------------
* Drug: Simultaneous ARV and antiMTB
* Drug: Deferred RV and antiMTB treatment


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: HIV infected < 200 CD4+ cells/mL Active pulmonary tuberculosis (with or without extrapulmonary involvement) Exclusion Criteria: Meningeal tuberculosis Unable to attend 96 wk follow-up

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1<br>Receives both, simultaneously antiretroviral therapy and antituberculosis therapy | Drug: Simultaneous ARV and antiMTB<br>* Receives both, simultaneously antiretroviral therapy and antituberculosis therapy<br>* Other names: Truvada;|
| Experimental: Group 2<br>Receives only antituberculosis therapy, and 2 months afterwards antiretroviral therapy | Drug: Deferred RV and antiMTB treatment<br>* Receives only antituberculosis therapy and 2 months afterwards antiretroviral therapy<br>* Other names: Truvada;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to remission of signs and symptoms of active tuberculosis as well as general symptoms. |  | 96 wk | 
| Time to negative measurement of mycobacterial load in body fluids or affected tissues |  | 24 wk | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CD4+ cell count increase |  | 24 wk | 
| Lymphoproliferative response to specific antigens against Mtb |  | 24 wk | 
| Time to undetectable HIV plasma load; HIV genotype |  | 24 wk | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Enzyme-Linked ImmunoSpot, Deferred treatment, Immune Recovery Inflammatory Syndrome