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Sponsors and Collaborators: |
University of Chicago Abbott |
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Information provided by: | University of Chicago |
ClinicalTrials.gov Identifier: | NCT00145795 |
Our goal is to determine if a change in therapy to one containing Kaletra can improve the immune response in patients who have previously been immune partial responders or non-responders. We also are interested in knowing if this agent improves immune response by affecting CD4 + T cell death (apoptosis) or by further inhibiting (preventing) ongoing, low-level, viral replication to levels below detection by current viral load measurements. This will help us understand why immune responses to effective antiretroviral therapy are so different and help determine some possible guidelines for managing patients with poor immune responses.
Hypothesis: Patients with poor immune responses to HAART who receive Kaletra in place of their current PI or NNRTI while continuing their current 2 NRTI backbone will have improved immune response to therapy compared to patients who continue their current regimen.
Condition | Intervention | Phase |
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HIV Infections |
Drug: Kaletra + Current Dual NRTI Backbone Drug: Current Regimen |
Phase IV |
Study Type: | Interventional |
Study Design: | Treatment, Randomized, Open Label, Active Control, Crossover Assignment |
Official Title: | Randomized Trial of a Switch to a Kaletra + Current Dual NRTI Backbone Versus Continuation of the Current Regimen in Patients With Poor Immune Responses to HAART in Patients With Complete Viral Suppression: A Pilot Study |
Estimated Enrollment: | 40 |
Study Start Date: | April 2004 |
Estimated Study Completion Date: | June 2008 |
Estimated Primary Completion Date: | December 2008 (Final data collection date for primary outcome measure) |
Arms | Assigned Interventions |
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1: Experimental
Kaletra + Current Dual NRTI Backbone
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Drug: Kaletra + Current Dual NRTI Backbone
study accrual closed
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2: Active Comparator
Current Regimen
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Drug: Current Regimen
study accrual closed
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To our knowledge our study is the first study showing persistent apoptosis in a subgroup of patients with complete viral suppression in association with poor immune recovery. Immune alterations independent of active viral replication may be responsible. Recent data suggests that immune responses to antiretroviral therapy depend on residual or restored thymic function. Improved CD4+ counts in patients despite virologic treatment failure are associated with greater thymic function, while poor T cell responses despite suppression of HIV are seen with decreased thymic function. Discordant immune responses may also be due to differential effects of particular antiretroviral agents on T cell apoptosis independent of viral suppression. For example, protease inhibitors have been shown to decrease rates of apoptosis of uninfected T cells. Viral replication is never completely suppressed with HAART, even when patients have undetectable plasma HIV RNA. Therefore, varying degrees of low level viral replication or replication in certain cellular compartments may continue to drive T cell apoptosis. Finally, our data suggests that ex vivo rates of PBMC apoptosis could potentially be used predict immune recovery or identify subgroups of patients who may benefit most from changes in HAART or adjunctive immunomodulatory therapies.
At this time, although there are excellent guidelines for how to evaluate and change therapy for patients with virologic failure, there are no recommendation and little data on approaches or strategies to change therapy for patients with poor immune responses. Kaletra (lopinavir/ritonavir) may be of benefit to patients with poor immune responses to HAART despite viral suppression. Kaletra may have greater potency and better suppression of viral replication that is below the level of detection by plasma PCR for HIV-1 RNA. Kaletra also has an excellent pharmacokinetic profile which may result in superior inhibition of T cell apoptosis in vivo.
Ages Eligible for Study: | 18 Years to 75 Years |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Exclusion Criteria:
United States, Illinois | |
University of Illinois at Chicago | |
Chicago, Illinois, United States, 60607 |
Principal Investigator: | David Pitrak, MD | University of Chicago |
Responsible Party: | University of Chicago ( David Pitrak, MD ) |
Study ID Numbers: | 11711B |
Study First Received: | September 1, 2005 |
Last Updated: | January 2, 2008 |
ClinicalTrials.gov Identifier: | NCT00145795 |
Health Authority: | United States: Institutional Review Board |
HIV HAART (Highly Active Anti-Retroviral Therapy) partial immune response no immune response Treatment Experienced |
Virus Diseases Sexually Transmitted Diseases, Viral Lopinavir HIV Infections |
Sexually Transmitted Diseases Acquired Immunodeficiency Syndrome Retroviridae Infections Immunologic Deficiency Syndromes |
Anti-Infective Agents Communicable Diseases RNA Virus Infections HIV Protease Inhibitors Slow Virus Diseases Anti-HIV Agents Immune System Diseases Molecular Mechanisms of Pharmacological Action |
Enzyme Inhibitors Infection Antiviral Agents Pharmacologic Actions Protease Inhibitors Anti-Retroviral Agents Therapeutic Uses Lentivirus Infections |