A Research Study to See if a Change in Therapy for HIV Infection Can Improve the Immune Response to Treatment

NCT00145795 | Completed Phase 4 Results DMC

• 1 other identifier: 11711B
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

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 cluster of differentiation 4 (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 Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) while continuing their current 2 NRTI backbone will have improved immune response to therapy compared to patients who continue their current regimen.

Conditions

HIV Infections

Keywords

HIV; HAART (Highly Active Anti-Retroviral Therapy) partial immune response; no immune response; Treatment Experienced

Outcome Measures

Primary Outcomes (2)

• Immune Reconstitution [3 Months]

  Immune reconstitution is defined as the absolute CD4+ lymphocyte count after 3 months of therapy. Absolute CD4+ T cell count, our measure of immune recovery, was assessed in the clinical laboratory using fluorescent labeled monoclonal antibodies to the CD4 on lymphocytes. This is the main target cell for HIV infection. The absolute CD4+ T cell count is also the only clinically validated surrogate marker of immune dysfunction in HIV. CD4+ count is also our best predictor of morbidity and mortality outcomes.

  3 months

• Immune Reconstitution [6 Months]

  Immune reconstitution is defined as the absolute CD4+ lymphocyte count after 6 months of therapy. Absolute CD4+ T cell count, our measure of immune recovery, was assessed in the clinical laboratory using fluorescent labeled monoclonal antibodies to the CD4 on lymphocytes. This is the main target cell for HIV infection. The absolute CD4+ T cell count is also the only clinically validated surrogate marker of immune dysfunction in HIV. CD4+ count is also our best predictor of morbidity and mortality outcomes.

  6 months

Secondary Outcomes (8)

• Rates of ex Vivo T Cell Apoptosis: CD4+ Memory Cell Population [3 Months]

  3 months

• Rates of ex Vivo T Cell Apoptosis: CD4+ naïve Cell Population [3 Months]

  3 months

• Rates of ex Vivo T Cell Apoptosis: CD4+ Memory Cell Population [6 Months]

  6 months

• Rates of ex Vivo T Cell Apoptosis: CD4+ naïve Cell Population [6 Months]

  6 months

• Rates of ex Vivo T Cell Apoptosis: CD8+ Cell Population [3 Months]

  3 months

Study Arms (2)

Kaletra + Current Dual NRTI Backbone

EXPERIMENTAL

Patients in this arm received Kaletra in addition to their current Dual NRTI Backbone.

Drug: Kaletra + Current Dual NRTI Backbone

Current Regimen

ACTIVE COMPARATOR

Patients in this study arm continued their current regimen.

Drug: Current Regimen

Interventions

Kaletra + Current Dual NRTI Backbone DRUG

Also known as: Lopinavir/ritonavir (LPV/r) + Current Dual NRTI Backbone

Kaletra + Current Dual NRTI Backbone

Current Regimen DRUG

Also known as: Current HIV treatment regimen

Current Regimen

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• HIV Infection documented CD4+ count within the last 30 days (or drawn with screening labs)
• Currently on a stable 3-drug HAART regimen including 2 NRTIs for \> 6 month viral load (VL) \< 50/mm3 for \> 6 months, last within the last 30 days (or drawn with screening labs)
• Partial immune responder or immune non-responder
• Age \> 18 years
• Labs (drawn at screening)
• Alanine transaminase (ALT) \< 5 X the upper limit of normal (ULN)
• Total bili \< 2 X ULN
• Creatinine \< 2.0 mg/dL

You may not qualify if:

• Prior therapy with Kaletra
• Known hypersensitivity to Ritonavir
• Therapy the drugs with potential serious drug interactions: flecainide, propafenone, astemizole, terfenadine, rifampin, dihydroergotamine, ergonovine, ergotamine, methylergonovine, cisapride, pimozide, lovastatin, simvastatin, midazolam, triazolam, and St. John's wart.
• Pregnancy; breast feeding
• Current malignancy requiring CT
• Use of systemic corticosteroids, immunosuppressive, or cytotoxic agents within the last 45 days
• Fever and/or evidence of an active infectious complication
• Currently in another interventional clinical trial
• Receiving Interleukin-2 (IL-2) or any other cytokine or growth factor
• Enrollment in another interventional clinical trial

Sponsors & Collaborators

• University of Chicago: lead
• Abbott: collaborator

Study Sites (1)

University of Illinois at Chicago

Chicago, Illinois, 60607, United States

Location

Related Publications (1)

• Pitrak DL, Estes R, Novak RM, Linnares-Diaz M, Tschampa JM. Beneficial effects of a switch to a Lopinavir/ritonavir-containing regimen for patients with partial or no immune reconstitution with highly active antiretroviral therapy despite complete viral suppression. AIDS Res Hum Retroviruses. 2011 Jun;27(6):659-67. doi: 10.1089/aid.2010.0230. Epub 2010 Dec 16.

  PMID: 21054216 RESULT

MeSH Terms

Conditions

HIV Infections

Interventions

lopinavir-ritonavir drug combination; Lopinavir; Ritonavir

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles

Results Point of Contact

• Title: Dr. David Pitrak
• Organization: The University of Chicago Department of Health Studies, Section of Infectious Diseases and Global Health

dpitrak@medicine.bsd.uchicago.edu

(773) 702-2710

Study Officials

• David Pitrak, MD

  University of Chicago

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 1, 2005
• First Posted: September 5, 2005
• Study Start: April 1, 2004
• Primary Completion: June 1, 2009
• Study Completion: December 1, 2009
• Last Updated: June 15, 2022
• Results First Posted: August 27, 2013

Record last verified: 2022-05

Locations

US (1)