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

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

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

Study Overview

• Status: Completed
• Conditions: HIV-1 Infection
• Intervention / Treatment: Biological: HIV DNA

Detailed Description

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 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 Type: Interventional
• Enrollment (Actual): 120
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Montpellier, France, 34295
    • University hospital Montpellier

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Causes and consequences of persistent de novo infection in virologic responders to HAART	Causes and consequences of persistent de novo infection in virologic responders to HAART	1 day

Collaborators and Investigators

• Sponsor: University Hospital, Montpellier
• Collaborators: Institute of Human Genetics, France
• Investigators: Principal Investigator: CHRISTINA PSOMAS, University Hospital of Montpellier, Montpellier, France, 34295

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2015
• Primary Completion (Actual): March 22, 2016
• Study Completion (Actual): December 31, 2016

Study Registration Dates

• First Submitted: November 19, 2015
• First Submitted That Met QC Criteria: November 19, 2015
• First Posted (Estimate): November 23, 2015

Study Record Updates

• Last Update Posted (Actual): July 7, 2021
• Last Update Submitted That Met QC Criteria: July 5, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Keywords: HAART; Aviremic HIV-1 infected patients; Integrase inhibitor Raltegravir; Ongoing HIV infection
• Additional Relevant MeSH Terms: Pathologic Processes; RNA Virus Infections; Virus Diseases; Blood-Borne Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; Disease Attributes; Slow Virus Diseases; HIV Infections; Infections; Communicable Diseases; Acquired Immunodeficiency Syndrome
• Other Study ID Numbers: 9503