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Sponsored by: |
Germans Trias i Pujol Hospital |
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Information provided by: | Germans Trias i Pujol Hospital |
ClinicalTrials.gov Identifier: | NCT00773708 |
This study aims to provide new knowledge about the pathogenesis of HIV infection, specifically, the role that immune activation and apoptotic activity play in immune recovery, and in particular, in the paradoxical immunologic response of some patients on antiretroviral therapy despite achievement of sustained and complete viral suppression. In this regard, we will prospectively evaluate the impact of intensification with Raltegravir in those "discordants" patients with high index of immune activation, measured as the percentage of CD8+HLADR+CD38+ cells. This will provide relevant information on the effectiveness of this drug in guided intensification regimens.
Condition | Intervention | Phase |
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HIV Infection |
Drug: raltegravir Drug: 1 PI plus 2 NRTI or 1 NNRTI plus 2 NRTIs |
Phase IV |
Study Type: | Interventional |
Study Design: | Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study |
Official Title: | Pilot Study to Assess the Role of Immune Activation and Apoptosis as a Marker for Treatment Intensification With Raltegravir in Hiv-Infected Patients on Antiretroviral Therapy With Long-Term Viral Suppression and Unfavourable Immunologic Response (Discordant Patients: v+i-) |
Estimated Enrollment: | 57 |
Study Start Date: | December 2008 |
Estimated Study Completion Date: | May 2010 |
Estimated Primary Completion Date: | May 2010 (Final data collection date for primary outcome measure) |
Arms | Assigned Interventions |
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1: Experimental
intensify their triple-drug therapy with Raltegravir (RAL)
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Drug: raltegravir
intensify their triple-drug therapy with Raltegravir (RAL):1 PI plus 2 NRTI plus RAL or 1 NNRTI plus 2 NRTIs plus RAL
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2: No Intervention
Continue wich desame antiretroviral therapy(1 PI plus 2 NRTI or 1 NNRTI plus 2 NRTIs)
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Drug: 1 PI plus 2 NRTI or 1 NNRTI plus 2 NRTIs
Continue wich desame antiretroviral therapy(1 PI plus 2 NRTI or 1 NNRTI plus 2 NRTIs)
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One of the many adverse consequences of the human immunodeficiency virus (HIV) infection is the increase in the rate of lymphocyte cell death (Badley AD, Blood. 2000; 96:2951-64). Increased lymphocyte death is associated with the level of activation of the immune system (Gougeon ML. Nat Rev Immunol. 2003: 3:392-404), along with the disregulation of the cytokine network and a plethora of cytotoxic effects induced by HIV proteins (Badley AD, Blood. 2000; 96:2951-64). Hence, cell death can be observed in vivo not only in CD4+ cells, which are the main target of HIV, but also in CD8 T cells. Current knowledge suggest that immune activation and different mechanisms of cell death play a determinant role in T-lymphocyte (CD4+) loss during HIV infection and recovery after HAART (Bofill M et al AIDS. 1996 :827-34).
Highly active antiretroviral treatment (HAART) induces a decline in the level of immune activation and lymphocyte apoptosis in HIV-infected patients as a result of a reduction in viral replication (Kolber MA, et al, Clin Immunol. 2007 [Epub ahead of print]). This reduction contributes to the recovery of immune system associated with antiretroviral therapy. In addition to this effect, which is induced through the reduction in viral load, antiretroviral therapy has been implicated in the regulation of apoptosis in different cell types, inhibiting or activating the process and influencing treatment efficacy and toxicity (Petit F, et al.Trends Pharmacol Sci. 2005. 26:258-64).
Interestingly, it is not always true that antiretroviral therapy and viral suppression are associated with progressive immune recovery. Approximately 30% of patients present a paradoxical response to treatment, achieving progressive increases in immunity (measured by CD4+ count) despite failing to achieve viral suppression, or, vice versa, patients who maintain or reduce CD4+ cell count despite achieving viral suppression. Indeed, it is well known that higher CD8 activation is associated with fewer treatment-mediated CD4 gain. Each 10% increase in activated CD8+HLADR+CD38+ mean 90 fewer CD4 cell gained (Hunt PW et al J Infect Dis. 2003. 187:1534-43). The failure of recover CD4 T cells may rely on a incomplete viral suppression than could be responsible for increased immune activation and lymphocyte death. Recently, it has been pointed out that intensification strategies may be useful in reducing activation and improving CD4 T cell recovery (Kolber MA, et al, Clin Immunol. 2007 [Epub ahead of print]).
Ages Eligible for Study: | 18 Years to 60 Years |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Patient having a diagnosis of HIV infection, on continuously HAART for at least 2 years, including:
Exclusion Criteria:
Responsible Party: | Lluita Sida Foundation ( Lluita Sida Foundation ) |
Study ID Numbers: | DISCOR-RAL |
Study First Received: | October 14, 2008 |
Last Updated: | October 14, 2008 |
ClinicalTrials.gov Identifier: | NCT00773708 |
Health Authority: | Spain: Ministry of Health |
HIV infection Discordant patient CD4 recovery |
intensification antiretroviral therapy raltegravir HIV-1 infected patient classified as "discordant" who showed high level of CD8+HLADR+CD38+ and cell death values at the screening |
Virus Diseases Sexually Transmitted Diseases, Viral Death HIV Infections |
Sexually Transmitted Diseases Acquired Immunodeficiency Syndrome Retroviridae Infections Immunologic Deficiency Syndromes |
RNA Virus Infections Slow Virus Diseases Immune System Diseases Lentivirus Infections Infection |