RALNOVO: Testing the Effect of Raltegravir on Persistent de Novo HIV Infection in Virologic Responders to Antiretroviral Therapy

Sponsor

University Hospital, Montpellier (Other)

Overall Status

Completed

CT.gov ID

NCT02611895

Collaborator

Institute of Human Genetics, France (Other)

120

Enrollment

Location

Arm

Actual Duration (Months)

5.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

There is a theoretical possibility of a complete suppression of HIV viral replication, subject to the use of highly active associations of more than 25 antiretroviral drugs currently available and good treatment adherence. But a key question remains: whether it can persist viral replication low noise HAART, since several arguments suggest a subclinical escape of the virus to HAART at least in some individuals. The technique proposed in this research consists of the detection and quantification of the linear viral cDNA intra cytoplasmic, as persistent novo infection marker in order to highlight the subclinical replication active in treatment of HIV-1 and consider an optimized therapeutic management of patients.

Main objective : Comparing the frequency of patients infected with HIV and treated effectively (HIV viral load undetectable plasma with conventional methods) having the HIV DNA into the cytoplasm of their CD4 + T cells from peripheral blood, as cellular infection marker novo persistent, among patients with a therapeutic regimen contains or not the viral integrase inhibitor raltegravir.

Secondary objectives

To evaluate the frequency of patients infected with HIV and treated effectively with the HIV DNA into the cytoplasm of their CD4 + T cells from peripheral blood
Evaluate the causes of persistent infection in de novo virological responders to treatment with ART: presence of the HIV genome encoding strains resistant to treatment ART ongoing noncompliance to treatment, type of antiretroviral therapy, CD4 nadir , pretreatment level of plasma HIV RNA, total duration of ART
Assess the impact of persistent novo infection virological responders: cell activation CD4 + and CD8 +, lack of immunological treatment response, changes in lymphocyte ratio T naïve / memory cells cells, the presence of transient increase viremia, residual viremia levels
Identify virological responders may benefit from treatment intensification

Condition or Disease	Intervention/Treatment	Phase
HIV-1 Infection	Biological: HIV DNA	N/A

Detailed Description

Secondary objectives

To evaluate the frequency of patients infected with HIV and treated effectively with the HIV DNA into the cytoplasm of their CD4 + T cells from peripheral blood
Evaluate the causes of persistent infection in de novo virological responders to treatment with ART: presence of the HIV genome encoding strains resistant to treatment ART ongoing noncompliance to treatment, type of antiretroviral therapy, CD4 nadir , pretreatment level of plasma HIV RNA, total duration of ART
Assess the impact of persistent novo infection virological responders: cell activation CD4 + and CD8 +, lack of immunological treatment response, changes in lymphocyte ratio T naïve / memory cells cells, the presence of transient increase viremia, residual viremia levels
Identify virological responders may benefit from treatment intensification Methods : HIV patients will be recruited by the doctors of Infectious and Tropical Diseases Service (MIT) in the Montpellier University Hospital.

As part of this research, three additional blood tubes (7 ml EDTA tube) will be collected, totaling 21 ml at the time of blood sampling carried out during two consultations scheduled as part of the usual care the pathology of HIV patients in the Service of MIT.

These consultations will be conducted at baseline and a further 3 to 6 months from the date of inclusion.

Study Design

Study Type:

Interventional

Actual Enrollment :

120 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Diagnostic

Official Title:

Testing the Effect of Raltegravir on Persistent de Novo HIV Infection in Virologic Responders to Antiretroviral Therapy ( RALNOVO )

Actual Study Start Date :

Mar 1, 2015

Actual Primary Completion Date :

Mar 22, 2016

Actual Study Completion Date :

Dec 31, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: HIV DNA Blood test : Quantitate the amount of HIV DNA harbored in the cytoplasm of peripheral blood CD4+ T cells	Biological: HIV DNA Quantitate the amount of HIV DNA harbored in the cytoplasm of peripheral blood CD4+ T cells

Arm

Intervention/Treatment

Experimental: HIV DNA

Blood test : Quantitate the amount of HIV DNA harbored in the cytoplasm of peripheral blood CD4+ T cells

Biological: HIV DNA

Quantitate the amount of HIV DNA harbored in the cytoplasm of peripheral blood CD4+ T cells

Outcome Measures

Primary Outcome Measures

Frequency of virologic responders harbouring intracytoplasmic HIV DNA in their peripheral blood CD4+ T cells, used as a surrogate marker of ongoing HIV infection, between subjects whose regimen contains or not the integrase inhibitor raltegravir. [1 day]
Frequency of virologic responders harbouring intracytoplasmic HIV DNA in their peripheral blood CD4+ T cells, used as a surrogate marker of ongoing HIV infection, between subjects whose regimen contains or not the integrase inhibitor raltegravir.

Secondary Outcome Measures

Causes and consequences of persistent de novo infection in virologic responders to HAART [1 day]
Causes and consequences of persistent de novo infection in virologic responders to HAART

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age > or = 18 years
HIV-1 infection
Current number of T CD4+ lymphocytes > 200 cells / mm3 for 6 moths before inclusion
Efficient and well tolerated antiretroviral treatment for more than 12 months
HIV-1 viral load < 50 copies/ml for more than 12 months before inclusion
Patient able to understand the nature, the objective and the methods of the study
Patient having signed the informed consent
Affiliation to French Social Security System

Exclusion Criteria:

Patient is currently participating or has participated in a study (within the exclusion period defined by this study)
Patient is pregnant or breastfeeding