Effect of Cytoreductive Chemotherapy and a CCR5 Coreceptor Antagonist on HIV-1 Eradication

Study Overview
=================
Brief Summary
-----------------
Effect on HIV-1 cell reservoirs of the concomitant administration of intensive chemotherapy and the pharmacological blockade of CCR5 coreceptors: a pilot, open, randomized, and controlled clinical trial.

Official Title
-----------------
Effect of Cytoreductive Chemotherapy and a CCR5 Coreceptor Antagonist on HIV-1 Eradication

Conditions
-----------------
HIV-1 Infection

Intervention / Treatment
-----------------
* Drug: Maraviroc


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients who give written consent to participate in the study Age between 18 and 65 years old, included. Chronic HIV-1 Demonstration of R5 viral tropism (use of CCR5 coreceptors) by genotyping in plasma samples stored Patients that are to be treated with intensive chemotherapy for non Hodgkin lymphoma With or without stable antiretroviral therapy Patients that are able to understand the purpose of the study and be available for scheduled appointments. Both in the case of female and male patients, the patient agrees to use a double barrier method of contraception from the moment of signing the informed consent until 3 months after the end of their participation in the study. Exclusion Criteria: To have planned antiretroviral treatment interruption during the participation in the study Hypersensitivity to products used in this study To be involved in another clinical trial or received an investigational drug within 3 months prior to the study initiation To have contraindications or limitations to perform leukapheresis

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 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 |
| --- | --- |
| No Intervention: Group 1 (Control)<br>Patients receiving intensive chemotherapy with/without stable antiretroviral therapy. Patients not receiving antiretroviral therapy will start it. Patients randomized to this group will not receive clinical trial treatment (neither Maraviroc or Placebo) | |
| Experimental: Group 2 (Treatment)<br>Patients receiving intensive chemotherapy with/without stable antiretroviral therapy and Maraviroc. Patients not receiving antiretroviral therapy will start this theraphy together with Maraviroc. | Drug: Maraviroc<br>* Patients randomized to experimental control will start Maraviroc treatment before, during and after chemotherapy until lymphocytes level recovery. Maraviroc Dose: 300 mg/12 hours For patients receiving an HIV-protease inhibitor (except tipranavir or Fosamprenavir), the dose will be reduced to 150 mg/12hours For patients receiving Efavirenz dose the dose will be 600 mg/12hours<br>* Other names: Celsentri;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| number of resting memory CD4+ T cells latently infected with replicative HIV-1, expressed as IUPM | Primary outcome will be measured before, during and after chemotherapy treatment until patient has reached normal lymphocytes levels | Same as chemotherapy treatment (expected average of 6 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proviral DNA (copies/million cells) | Secondary outcome will be measured before, during and after chemotherapy treatment until patient has reached normal lymphocytes levels | Same as chemotherapy treatment (expected average of 6 months) | 
| Effector T cells producing HIV-1 specific gamma interferon (cells/mm3) | Secondary outcome will be measured before, during and after chemotherapy treatment until patient has reached normal lymphocytes levels | Same as chemotherapy treatment (expected average of 6 months) | 
| Levels of HIV-1 antibodies | Secondary outcome will be measured before, during and after chemotherapy treatment until patient has reached normal lymphocytes levels | Same as chemotherapy treatment (expected average of 6 months) | 
| Percentage of CD4+ and CD8+ cells with immune activation markers | Secondary outcome will be measured before, during and after chemotherapy treatment until patient has reached normal lymphocytes levels | Same as chemotherapy treatment (expected average of 6 months) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
HIV-1, CCR5 coreceptors, Maraviroc