CD4 Cell Recovery in HIV-1 Patients Comparing 2 Treatment Regimes

This study has been completed.
Sponsor:
Information provided by:
University of Cologne
ClinicalTrials.gov Identifier:
NCT00966160
First received: August 25, 2009
Last updated: September 28, 2009
Last verified: August 2009
  Purpose

Therapy guidelines recommend the use of either the non-nucleoside reverse transcriptase inhibitor (NNRTI) efavirenz or a ritonavir-boostered protease inhibitor (PI) plus 2 nucleoside reverse transcriptase inhibitors (NRTI) as first-line treatment regimes of HIV-1 infection. Recent clinical studies suggest potential advantages of NNRTI- over PI-based regimes in therapy initiation due to lower rates of virologic failure and less metabolic side-effects. In contrast, PI regimes were claimed to cause greater increases in CD4 cell count than NNRTI regimes, which has been attributed to intrinsic antiapoptotic effects of the PI. However, it is still unclear whether the immunological response to a PI-containing regime is greater than to an NNRTI-containing regime, whether there is a difference in the extent of reduction of apoptosis between PI and NNRTI regimes and whether a difference in apoptosis is associated with a difference in CD4 cell recovery.

We conducted a controlled, long-term, random matched pair design study in HIV-1 infected individuals under sustained virologic suppression to evaluate in head-to-head comparison the clinical effects of a constant PI-based or NNRTI-based regime on CD4 cell recovery and the underlying molecular, biochemical and functional mechanisms.


Condition Intervention Phase
Acquired Immunodeficiency Syndrome
HIV Infections
Drug: Lopinavir/Ritonavir plus Lamivudine/Zidovudine
Drug: Efavirenz plus Lamivudine/Zidovudine
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single Blind (Investigator)
Primary Purpose: Treatment
Official Title: Phase 3, Single Center, Controlled, Investigator-blinded, Randomized Matched Pair Design Study of CD4 Cell Recovery in HIV-1 Patients With Sustained Virologic Response Comparing Protease Inhibitor and Non-nucleoside Reverse Transcriptase Inhibitor Based Treatment Regimes

Resource links provided by NLM:


Further study details as provided by University of Cologne:

Primary Outcome Measures:
  • Difference in changes of CD4 cell count between PI and NNRTI groups [ Time Frame: 420 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Evolution of CD4 cell counts [ Time Frame: 420 weeks ] [ Designated as safety issue: No ]
  • Molecular, biochemical and functional markers of CD4 cell apoptosis [ Time Frame: 420 weeks ] [ Designated as safety issue: No ]

Enrollment: 215
Study Start Date: January 1999
Study Completion Date: December 2008
Primary Completion Date: December 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: PI
400 mg lopinavir and 100 mg ritonavir (Kaletra capsules, Abbott Laboratories) twice daily plus 150 mg lamivudine (Epivir tablets, GlaxoSmithKline) and 300 mg zidovudine (Retrovir tablets, GlaxoSmithKline) twice daily over a 56-week run-in and a 420-week follow-up
Drug: Lopinavir/Ritonavir plus Lamivudine/Zidovudine
400 mg lopinavir and 100 mg ritonavir (Kaletra capsules, Abbott Laboratories) twice daily plus 150 mg lamivudine (Epivir tablets, GlaxoSmithKline) and 300 mg zidovudine (Retrovir tablets, GlaxoSmithKline) twice daily over 476 weeks
Active Comparator: NNRTI
600 mg efavirenz (Sustiva tablets, Bristol-Myers Squibb) once daily plus 150 mg lamivudine (Epivir tablets, GlaxoSmithKline) and 300 mg zidovudine (Retrovir tablets, GlaxoSmithKline) twice daily over a 56-week run-in and a 420-week follow-up
Drug: Efavirenz plus Lamivudine/Zidovudine
600 mg efavirenz (Sustiva tablets, Bristol-Myers Squibb) once daily plus 150 mg lamivudine (Epivir tablets, GlaxoSmithKline) and 300 mg zidovudine (Retrovir tablets, GlaxoSmithKline) twice daily over 476 weeks

  Eligibility

Ages Eligible for Study:   20 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Recent, non-acute HIV-1 infection
  • Caucasians
  • BMI between 17.5 and 30 kg/m2
  • CD4 count <200 cells/µl
  • Plasma viral load >100,000 HIV-1 RNA copies/ml

Exclusion Criteria:

  • Actual or previous antiretroviral therapy
  • Acute illness
  • Coinfection with HBV or HCV
  • Opportunistic infection (Pneumocystis jiroveci pneumonia, Toxoplasma gondii encephalitis, Mycobacterium ssp. infection, syphilis, cryptosporidiosis, cryptococcosis, aspergillosis, cytomegalovirus infection or progressive multifocal leukoencephalopathy)
  • Hepatic or renal disorder
  • Severe cardiovascular disease
  • Hematologic disorder
  • Autoimmune disorder
  • Diabetes mellitus or other severe endocrine disorder
  • Malignancy
  • Neurocognitive disorder
  • Psychiatric disorder
  • Drug or alcohol addiction
  • Chronic drug use (except of blood pressure-lowering or lipid-lowering drugs or proton-pump inhibitors)
  • Any acute medication within 7 days or vaccination within 30 days prior to entry
  • Pregnancy or lactation
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00966160

Locations
Germany
Medical Clinic I and Department of Pharmacology, University of Cologne
Cologne, Germany
Sponsors and Collaborators
University of Cologne
Investigators
Study Director: Dirk Taubert, MD PhD Department of Pharmacology, University of Cologne, Germany
  More Information

Publications:
Responsible Party: Dirk Taubert, University of Cologne
ClinicalTrials.gov Identifier: NCT00966160     History of Changes
Other Study ID Numbers: HIV-1999-LRE
Study First Received: August 25, 2009
Last Updated: September 28, 2009
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by University of Cologne:
treatment naive

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
HIV Infections
Immunologic Deficiency Syndromes
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Slow Virus Diseases
Immune System Diseases
Protease Inhibitors
Ritonavir
Lopinavir
Zidovudine
Lamivudine
Reverse Transcriptase Inhibitors
Efavirenz
Lamivudine, zidovudine drug combination
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antimetabolites
Nucleic Acid Synthesis Inhibitors
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Anti-HIV Agents
HIV Protease Inhibitors

ClinicalTrials.gov processed this record on April 15, 2014